Carrel name: keyword-ifn-cord Creating study carrel named keyword-ifn-cord Initializing database file: cache/cord-000018-amvlm09p.json key: cord-000018-amvlm09p authors: Pauli, Eva-K.; Schmolke, Mirco; Wolff, Thorsten; Viemann, Dorothee; Roth, Johannes; Bode, Johannes G.; Ludwig, Stephan title: Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression date: 2008-11-07 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000196 sha: doc_id: 18 cord_uid: amvlm09p file: cache/cord-000103-3zh8jmc2.json key: cord-000103-3zh8jmc2 authors: Caignard, Grégory; Komarova, Anastassia V.; Bouraï, Mehdi; Mourez, Thomas; Jacob, Yves; Jones, Louis M.; Rozenberg, Flore; Vabret, Astrid; Freymuth, François; Tangy, Frédéric; Vidalain, Pierre-Olivier title: Differential Regulation of Type I Interferon and Epidermal Growth Factor Pathways by a Human Respirovirus Virulence Factor date: 2009-09-18 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000587 sha: doc_id: 103 cord_uid: 3zh8jmc2 file: cache/cord-000125-uvf5qzfd.json key: cord-000125-uvf5qzfd authors: Kenworthy, Rachael; Lambert, Diana; Yang, Feng; Wang, Nan; Chen, Zihong; Zhu, Haizhen; Zhu, Fanxiu; Liu, Chen; Li, Kui; Tang, Hengli title: Short-hairpin RNAs delivered by lentiviral vector transduction trigger RIG-I-mediated IFN activation date: 2009-09-03 journal: Nucleic Acids Res DOI: 10.1093/nar/gkp714 sha: doc_id: 125 cord_uid: uvf5qzfd file: cache/cord-000403-vzbh457k.json key: cord-000403-vzbh457k authors: Zhang, Weijun; Lin, Yan; Bai, Yu; Tong, Tiegang; Wang, Qun; Liu, Nihong; Liu, Guangliang; Xiao, Yihong; Yang, Tao; Bu, Zhigao; Tong, Guangzhi; Wu, Donglai title: Identification of CD8(+ )cytotoxic T lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in BALB/c mice date: 2011-05-30 journal: Virol J DOI: 10.1186/1743-422x-8-263 sha: doc_id: 403 cord_uid: vzbh457k file: cache/cord-000478-88wo4xen.json key: cord-000478-88wo4xen authors: Gowen, Brian B.; Ennis, Jane; Russell, Andrew; Sefing, Eric J.; Wong, Min-Hui; Turner, Jeffrey title: Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection date: 2011-10-24 journal: PLoS One DOI: 10.1371/journal.pone.0026072 sha: doc_id: 478 cord_uid: 88wo4xen file: cache/cord-000104-3b8b8p61.json key: cord-000104-3b8b8p61 authors: McWhirter, Sarah M.; Barbalat, Roman; Monroe, Kathryn M.; Fontana, Mary F.; Hyodo, Mamoru; Joncker, Nathalie T.; Ishii, Ken J.; Akira, Shizuo; Colonna, Marco; Chen, Zhijian J.; Fitzgerald, Katherine A.; Hayakawa, Yoshihiro; Vance, Russell E. title: A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP date: 2009-08-31 journal: J Exp Med DOI: 10.1084/jem.20082874 sha: doc_id: 104 cord_uid: 3b8b8p61 file: cache/cord-000164-094d0rn6.json key: cord-000164-094d0rn6 authors: Suthar, Mehul S.; Ma, Daphne Y.; Thomas, Sunil; Lund, Jennifer M.; Zhang, Nu; Daffis, Stephane; Rudensky, Alexander Y.; Bevan, Michael J.; Clark, Edward A.; Kaja, Murali-Krishna; Diamond, Michael S.; Gale, Michael title: IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity date: 2010-02-05 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1000757 sha: doc_id: 164 cord_uid: 094d0rn6 file: cache/cord-000554-p4ufea6x.json key: cord-000554-p4ufea6x authors: Gao, Wei; Sun, Wenkui; Qu, Bingqian; Cardona, Carol J.; Powell, Kira; Wegner, Marta; Shi, Yi; Xing, Zheng title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus date: 2012-01-18 journal: PLoS One DOI: 10.1371/journal.pone.0030328 sha: doc_id: 554 cord_uid: p4ufea6x file: cache/cord-001273-plz1ja2e.json key: cord-001273-plz1ja2e authors: Dussurget, Olivier; Bierne, Hélène; Cossart, Pascale title: The bacterial pathogen Listeria monocytogenes and the interferon family: type I, type II and type III interferons date: 2014-04-28 journal: Front Cell Infect Microbiol DOI: 10.3389/fcimb.2014.00050 sha: doc_id: 1273 cord_uid: plz1ja2e file: cache/cord-000409-lpf9lpky.json key: cord-000409-lpf9lpky authors: Chen, Yongwen; Wu, Shengxi; Guo, Guoning; Fei, Lei; Guo, Sheng; Yang, Chengying; Fu, Xiaolan; Wu, Yuzhang title: Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection date: 2011-07-07 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1001347 sha: doc_id: 409 cord_uid: lpf9lpky file: cache/cord-001542-f089bs8r.json key: cord-001542-f089bs8r authors: Lai, Kang Yiu; Ng, Wing Yiu George; Cheng, Fan Fanny title: Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus date: 2014-11-28 journal: Infect Dis Poverty DOI: 10.1186/2049-9957-3-43 sha: doc_id: 1542 cord_uid: f089bs8r file: cache/cord-000725-rafwlw0t.json key: cord-000725-rafwlw0t authors: Hindinger, Claudia; Bergmann, Cornelia C.; Hinton, David R.; Phares, Timothy W.; Parra, Gabriel I.; Hussain, Shabbir; Savarin, Carine; Atkinson, Roscoe D.; Stohlman, Stephen A. title: IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date: 2012-07-27 journal: PLoS One DOI: 10.1371/journal.pone.0042088 sha: doc_id: 725 cord_uid: rafwlw0t file: cache/cord-001124-qcjbtflt.json key: cord-001124-qcjbtflt authors: Carrero, Javier Antonio title: Confounding roles for type I interferons during bacterial and viral pathogenesis date: 2013-10-24 journal: International Immunology DOI: 10.1093/intimm/dxt050 sha: doc_id: 1124 cord_uid: qcjbtflt file: cache/cord-001359-c1uom5f7.json key: cord-001359-c1uom5f7 authors: Oslund, Karen L.; Zhou, Xu; Lee, Boram; Zhu, Lingxiang; Duong, Trang; Shih, Robert; Baumgarth, Nicole; Hung, Li-Yin; Wu, Reen; Chen, Yin title: Synergistic Up-Regulation of CXCL10 by Virus and IFN γ in Human Airway Epithelial Cells date: 2014-07-17 journal: PLoS One DOI: 10.1371/journal.pone.0100978 sha: doc_id: 1359 cord_uid: c1uom5f7 file: cache/cord-001808-47496o0e.json key: cord-001808-47496o0e authors: Bayat, Ahmad; Burbelo, Peter D.; Browne, Sarah K.; Quinlivan, Mark; Martinez, Bianca; Holland, Steven M.; Buvanendran, Asokumar; Kroin, Jeffrey S.; Mannes, Andrew J.; Breuer, Judith; Cohen, Jeffrey I.; Iadarola, Michael J. title: Anti-cytokine autoantibodies in postherpetic neuralgia date: 2015-10-20 journal: J Transl Med DOI: 10.1186/s12967-015-0695-6 sha: doc_id: 1808 cord_uid: 47496o0e file: cache/cord-002630-5616n73p.json key: cord-002630-5616n73p authors: Dargahi, Narges; Katsara, Maria; Tselios, Theodore; Androutsou, Maria-Eleni; de Courten, Maximilian; Matsoukas, John; Apostolopoulos, Vasso title: Multiple Sclerosis: Immunopathology and Treatment Update date: 2017-07-07 journal: Brain Sci DOI: 10.3390/brainsci7070078 sha: doc_id: 2630 cord_uid: 5616n73p file: cache/cord-003239-nph2ezii.json key: cord-003239-nph2ezii authors: Zhu, Zixiang; Du, Xiaoli; Li, Pengfei; Zhang, Xiangle; Yang, Fan; Cao, Weijun; Tian, Hong; Zhang, Keshan; Liu, Xiangtao; Zheng, Haixue title: Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction date: 2018-09-27 journal: Front Microbiol DOI: 10.3389/fmicb.2018.02326 sha: doc_id: 3239 cord_uid: nph2ezii file: cache/cord-001236-cgiok0ce.json key: cord-001236-cgiok0ce authors: Binjawadagi, Basavaraj; Dwivedi, Varun; Manickam, Cordelia; Ouyang, Kang; Torrelles, Jordi B; Renukaradhya, Gourapura J title: An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination date: 2014-03-24 journal: Int J Nanomedicine DOI: 10.2147/ijn.s59924 sha: doc_id: 1236 cord_uid: cgiok0ce file: cache/cord-001109-xs7df6a7.json key: cord-001109-xs7df6a7 authors: Tapia, Karla; Kim, Won-keun; Sun, Yan; Mercado-López, Xiomara; Dunay, Emily; Wise, Megan; Adu, Michael; López, Carolina B. title: Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity date: 2013-10-31 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1003703 sha: doc_id: 1109 cord_uid: xs7df6a7 file: cache/cord-000660-tsvzg0ax.json key: cord-000660-tsvzg0ax authors: Fensterl, Volker; Wetzel, Jaime L.; Ramachandran, Srividya; Ogino, Tomoaki; Stohlman, Stephen A.; Bergmann, Cornelia C.; Diamond, Michael S.; Virgin, Herbert W.; Sen, Ganes C. title: Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis date: 2012-05-17 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1002712 sha: doc_id: 660 cord_uid: tsvzg0ax file: cache/cord-001515-x11t9pbv.json key: cord-001515-x11t9pbv authors: Kosinska, Anna D.; Liu, Jia; Lu, Mengji; Roggendorf, Michael title: Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck date: 2014-12-23 journal: Med Microbiol Immunol DOI: 10.1007/s00430-014-0379-5 sha: doc_id: 1515 cord_uid: x11t9pbv file: cache/cord-001901-2s6hpakk.json key: cord-001901-2s6hpakk authors: Kwok, Hoi-Hin; Poon, Po-Ying; Fok, Siu-Ping; Ying-Kit Yue, Patrick; Mak, Nai-Ki; Chan, Michael Chi-Wai; Peiris, Joseph Sriyal Malik; Wong, Ricky Ngok-Shun title: Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells date: 2016-01-06 journal: Sci Rep DOI: 10.1038/srep18941 sha: doc_id: 1901 cord_uid: 2s6hpakk file: cache/cord-002238-fyztb8d9.json key: cord-002238-fyztb8d9 authors: Young, D. F.; Andrejeva, J.; Li, X.; Inesta-Vaquera, F.; Dong, C.; Cowling, V. H.; Goodbourn, S.; Randall, R. E. title: Human IFIT1 Inhibits mRNA Translation of Rubulaviruses but Not Other Members of the Paramyxoviridae Family date: 2016-09-29 journal: J Virol DOI: 10.1128/jvi.01056-16 sha: doc_id: 2238 cord_uid: fyztb8d9 file: cache/cord-001676-68y733y3.json key: cord-001676-68y733y3 authors: Shoemaker, Jason E.; Fukuyama, Satoshi; Eisfeld, Amie J.; Zhao, Dongming; Kawakami, Eiryo; Sakabe, Saori; Maemura, Tadashi; Gorai, Takeo; Katsura, Hiroaki; Muramoto, Yukiko; Watanabe, Shinji; Watanabe, Tokiko; Fuji, Ken; Matsuoka, Yukiko; Kitano, Hiroaki; Kawaoka, Yoshihiro title: An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation date: 2015-06-05 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1004856 sha: doc_id: 1676 cord_uid: 68y733y3 file: cache/cord-001546-ndz3oarf.json key: cord-001546-ndz3oarf authors: Ayithan, Natarajan; Bradfute, Steven B.; Anthony, Scott M.; Stuthman, Kelly S.; Bavari, Sina; Bray, Mike; Ozato, Keiko title: Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date: 2015-02-26 journal: PLoS One DOI: 10.1371/journal.pone.0118345 sha: doc_id: 1546 cord_uid: ndz3oarf file: cache/cord-001848-idmj2d7p.json key: cord-001848-idmj2d7p authors: Onabajo, Olusegun O.; Porter-Gill, Patricia; Paquin, Ashley; Rao, Nina; Liu, Luyang; Tang, Wei; Brand, Nathan; Prokunina-Olsson, Ludmila title: Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells date: 2015-11-01 journal: J Interferon Cytokine Res DOI: 10.1089/jir.2014.0161 sha: doc_id: 1848 cord_uid: idmj2d7p file: cache/cord-001964-iy6qzq58.json key: cord-001964-iy6qzq58 authors: Muñoz-González, Sara; Pérez-Simó, Marta; Colom-Cadena, Andreu; Cabezón, Oscar; Bohórquez, José Alejandro; Rosell, Rosa; Pérez, Lester Josué; Marco, Ignasi; Lavín, Santiago; Domingo, Mariano; Ganges, Llilianne title: Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar date: 2016-02-26 journal: PLoS One DOI: 10.1371/journal.pone.0149469 sha: doc_id: 1964 cord_uid: iy6qzq58 file: cache/cord-004400-li1sc47z.json key: cord-004400-li1sc47z authors: Ma, Jingjiao; Wu, Rujuan; Xu, Guanlong; Cheng, Yuqiang; Wang, Zhaofei; Wang, Heng’an; Yan, Yaxian; Li, Jinxiang; Sun, Jianhe title: Acetylation at K108 of the NS1 protein is important for the replication and virulence of influenza virus date: 2020-02-24 journal: Vet Res DOI: 10.1186/s13567-020-00747-3 sha: doc_id: 4400 cord_uid: li1sc47z file: cache/cord-002079-jne14jqf.json key: cord-002079-jne14jqf authors: MacParland, Sonya A.; Ma, Xue-Zhong; Chen, Limin; Khattar, Ramzi; Cherepanov, Vera; Selzner, Markus; Feld, Jordan J.; Selzner, Nazia; McGilvray, Ian D. title: Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date: 2016-05-27 journal: J Virol DOI: 10.1128/jvi.02557-15 sha: doc_id: 2079 cord_uid: jne14jqf file: cache/cord-004341-co9s26x1.json key: cord-004341-co9s26x1 authors: Thukral, Akanksha; Ross, Kathleen; Hansen, Chungyi; Phanse, Yashdeep; Narasimhan, Balaji; Steinberg, Howard; Talaat, Adel M. title: A single dose polyanhydride-based nanovaccine against paratuberculosis infection date: 2020-02-14 journal: NPJ Vaccines DOI: 10.1038/s41541-020-0164-y sha: doc_id: 4341 cord_uid: co9s26x1 file: cache/cord-001397-nrq4ncdf.json key: cord-001397-nrq4ncdf authors: Mlera, Luwanika; Melik, Wessam; Bloom, Marshall E. title: The role of viral persistence in flavivirus biology date: 2014-05-12 journal: Pathogens and Disease DOI: 10.1111/2049-632x.12178 sha: doc_id: 1397 cord_uid: nrq4ncdf file: cache/cord-002068-e071ciil.json key: cord-002068-e071ciil authors: Feng, Min; Dai, Manman; Xie, Tingting; Li, Zhenhui; Shi, Meiqing; Zhang, Xiquan title: Innate Immune Responses in ALV-J Infected Chicks and Chickens with Hemangioma In Vivo date: 2016-05-25 journal: Front Microbiol DOI: 10.3389/fmicb.2016.00786 sha: doc_id: 2068 cord_uid: e071ciil file: cache/cord-001834-6xf4o3oy.json key: cord-001834-6xf4o3oy authors: Sung, Pil Soo; Shin, Eui-Cheol; Yoon, Seung Kew title: Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection date: 2015-10-07 journal: Int J Mol Sci DOI: 10.3390/ijms161023683 sha: doc_id: 1834 cord_uid: 6xf4o3oy file: cache/cord-002670-rjrw875d.json key: cord-002670-rjrw875d authors: Chen, Jidang; Ly, Hinh title: Immunosuppression by viral N proteins date: 2017-06-22 journal: Oncotarget DOI: 10.18632/oncotarget.18597 sha: doc_id: 2670 cord_uid: rjrw875d file: cache/cord-002937-7xauocti.json key: cord-002937-7xauocti authors: Huang, Chung-Guei; Lee, Li-Ang; Wu, Yi-Cheng; Hsiao, Mei-Jen; Horng, Jim-Tong; Kuo, Rei-Lin; Huang, Chih-Heng; Lin, Ya-Chu; Tsao, Kuo-Chien; Chen, Min-Chi; Chen, Tse-Ching; Shih, Shin-Ru title: A pilot study on primary cultures of human respiratory tract epithelial cells to predict patients’ responses to H7N9 infection date: 2018-02-20 journal: Oncotarget DOI: 10.18632/oncotarget.24537 sha: doc_id: 2937 cord_uid: 7xauocti file: cache/cord-002021-67ao8chx.json key: cord-002021-67ao8chx authors: Kim, Seong Bum; Choi, Jin Young; Uyangaa, Erdenebileg; Patil, Ajit Mahadev; Hossain, Ferdaus Mohd Altaf; Hur, Jin; Park, Sang-Youel; Lee, John-Hwa; Kim, Koanhoi; Eo, Seong Kug title: Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses date: 2016-04-18 journal: J Neuroinflammation DOI: 10.1186/s12974-016-0551-5 sha: doc_id: 2021 cord_uid: 67ao8chx file: cache/cord-003382-v3w1wi5c.json key: cord-003382-v3w1wi5c authors: Rahmatpanah, Farah; 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S. title: Multiple mechanisms for HSV-1 induction of interferon α production by peripheral blood mononuclear cells date: 2003 journal: Arch Virol DOI: 10.1007/s00705-002-0912-5 sha: doc_id: 339991 cord_uid: k8z6v2vx file: cache/cord-353957-0pjg25kn.json key: cord-353957-0pjg25kn authors: Chen, Shilong; Wang, Long; Chen, Jieying; Zhang, Lanlan; Wang, Song; Goraya, Mohsan U.; Chi, Xiaojuan; Na, Yang; Shao, Wenhan; Yang, Zhou; Zeng, Xiancheng; Chen, Shaoying; Chen, Ji-Long title: Avian Interferon-Inducible Transmembrane Protein Family Effectively Restricts Avian Tembusu Virus Infection date: 2017-04-20 journal: Front Microbiol DOI: 10.3389/fmicb.2017.00672 sha: doc_id: 353957 cord_uid: 0pjg25kn file: cache/cord-341478-bicg5ozr.json key: cord-341478-bicg5ozr authors: Aurisicchio, L; Bujard, H; Hillen, W; Cortese, R; Ciliberto, G; La Monica, N; Palombo, F title: Regulated and prolonged expression of mIFNα in immunocompetent mice mediated by a helper-dependent adenovirus vector date: 2002-01-30 journal: Gene Ther DOI: 10.1038/sj.gt.3301596 sha: doc_id: 341478 cord_uid: bicg5ozr file: cache/cord-344093-3bniy5b5.json key: cord-344093-3bniy5b5 authors: Peteranderl, Christin; Herold, Susanne title: The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond date: 2017-03-22 journal: Front Immunol DOI: 10.3389/fimmu.2017.00313 sha: doc_id: 344093 cord_uid: 3bniy5b5 file: cache/cord-348684-xbxwpmxq.json key: cord-348684-xbxwpmxq authors: Liu, Bao-qin; Jin, Jin; Li, Yi-yuan title: Ubiquitination modification: critical regulation of IRF family stability and activity date: 2020-10-30 journal: Sci China Life Sci DOI: 10.1007/s11427-020-1796-0 sha: doc_id: 348684 cord_uid: xbxwpmxq file: cache/cord-342063-1si0qrrx.json key: cord-342063-1si0qrrx authors: Battesti, G.; Descamps, V. title: Negative tests for SARS‐CoV‐2 infection do not rule out its responsibility for chilblains date: 2020-08-13 journal: Br J Dermatol DOI: 10.1111/bjd.19483 sha: doc_id: 342063 cord_uid: 1si0qrrx file: cache/cord-353062-c6luoo3m.json key: cord-353062-c6luoo3m authors: Lauber, C; Vieyres, G; Terczyńska-Dyla, E; Anggakusuma; Dijkman, R; Gad, H H; Akhtar, H; Geffers, R; Vondran, F W R; Thiel, V; Kaderali, L; Pietschmann, T; Hartmann, R title: Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells date: 2015-09-01 journal: Genes Immun DOI: 10.1038/gene.2015.23 sha: doc_id: 353062 cord_uid: c6luoo3m file: cache/cord-348993-8r4fhzlm.json key: cord-348993-8r4fhzlm authors: Tomosada, Yohsuke; Chiba, Eriko; Zelaya, Hortensia; Takahashi, Takuya; Tsukida, Kohichiro; Kitazawa, Haruki; Alvarez, Susana; Villena, Julio title: Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection date: 2013-08-15 journal: BMC Immunol DOI: 10.1186/1471-2172-14-40 sha: doc_id: 348993 cord_uid: 8r4fhzlm file: cache/cord-353337-o302vxqm.json key: cord-353337-o302vxqm authors: Visser, Linda J.; Aloise, Chiara; Swatek, Kirby N.; Medina, Gisselle N.; Olek, Karin M.; Rabouw, Huib H.; de Groot, Raoul J.; Langereis, Martijn A.; de los Santos, Teresa; Komander, David; Skern, Tim; van Kuppeveld, Frank J. M. title: Dissecting distinct proteolytic activities of FMDV L(pro) implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression date: 2020-07-15 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1008702 sha: doc_id: 353337 cord_uid: o302vxqm file: cache/cord-346836-6jyv0q5e.json key: cord-346836-6jyv0q5e authors: Ikegami, Tetsuro; Makino, Shinji title: The Pathogenesis of Rift Valley Fever date: 2011-05-06 journal: Viruses DOI: 10.3390/v3050493 sha: doc_id: 346836 cord_uid: 6jyv0q5e file: cache/cord-343963-99rd3o79.json key: cord-343963-99rd3o79 authors: Wong, Mun-Teng; Chen, Steve S-L title: Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection date: 2014-12-29 journal: Cell Mol Immunol DOI: 10.1038/cmi.2014.127 sha: doc_id: 343963 cord_uid: 99rd3o79 file: cache/cord-345854-f0dq94j1.json key: cord-345854-f0dq94j1 authors: Chong, Wai Po; Ip, WK Eddie; Tso, Gloria Hoi Wan; Ng, Man Wai; Wong, Wilfred Hing Sang; Law, Helen Ka Wai; Yung, Raymond WH; Chow, Eudora Y; Au, KL; Chan, Eric YT; Lim, Wilina; Peiris, JS Malik; Lau, Yu Lung title: The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome date: 2006-05-04 journal: BMC Infect Dis DOI: 10.1186/1471-2334-6-82 sha: doc_id: 345854 cord_uid: f0dq94j1 file: cache/cord-342800-62jklwiy.json key: cord-342800-62jklwiy authors: Xu, Shuqin; Yang, Kunpeng; Li, Rose; Zhang, Lu title: mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection date: 2020-09-09 journal: Int J Mol Sci DOI: 10.3390/ijms21186582 sha: doc_id: 342800 cord_uid: 62jklwiy file: cache/cord-337458-dc90ecfe.json key: cord-337458-dc90ecfe authors: Markwalter, Christine F.; Kantor, Andrew G.; Moore, Carson P.; Richardson, Kelly A.; Wright, David W. title: Inorganic Complexes and Metal-Based Nanomaterials for Infectious Disease Diagnostics date: 2018-12-04 journal: Chem Rev DOI: 10.1021/acs.chemrev.8b00136 sha: doc_id: 337458 cord_uid: dc90ecfe file: cache/cord-347225-gh51ag2x.json key: cord-347225-gh51ag2x authors: Fu, Weihui; Liu, Yan; Xia, Lu; Li, Min; Song, Zhigang; Hu, Huiliang; Yang, Zongguo; Wang, Lin; Cheng, Xiaobo; Wang, Mei; Jiang, Rongrong; Liu, Li; Mao, Xiaoting; Chen, Jun; Ling, Yun; Zhang, Lin; Yan, Jin; Shan, Fei; Steinhart, Corklin; Zhang, Xiaoyan; Zhu, Tongyu; Xu, Jianqing; Lu, Hongzhou title: A clinical pilot study on the safety and efficacy of aerosol inhalation treatment of IFN-κ plus TFF2 in patients with moderate COVID-19 date: 2020-07-29 journal: EClinicalMedicine DOI: 10.1016/j.eclinm.2020.100478 sha: doc_id: 347225 cord_uid: gh51ag2x file: cache/cord-347946-i6kx3n6m.json key: cord-347946-i6kx3n6m authors: Raison, Charles L; Miller, Andrew H title: Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance date: 2016-09-15 journal: Neuropsychopharmacology DOI: 10.1038/npp.2016.194 sha: doc_id: 347946 cord_uid: i6kx3n6m file: cache/cord-354730-hfau2odb.json key: cord-354730-hfau2odb authors: Wang, Rong; Zhang, Yan-Jin title: Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus date: 2014-07-03 journal: Biomed Res Int DOI: 10.1155/2014/315470 sha: doc_id: 354730 cord_uid: hfau2odb file: cache/cord-347200-dtwhd6zy.json key: cord-347200-dtwhd6zy authors: Ivanova, Daria; Krempels, Ryan; Ryfe, Jennyfer; Weitzman, Kaitlyn; Stephenson, David; Gigley, Jason P. title: NK Cells in Mucosal Defense against Infection date: 2014-08-14 journal: Biomed Res Int DOI: 10.1155/2014/413982 sha: doc_id: 347200 cord_uid: dtwhd6zy file: cache/cord-347298-7kqrl3rv.json key: cord-347298-7kqrl3rv authors: Hedger, M.P. title: Immunology of the Testis and Male Reproductive Tract date: 2010-07-12 journal: Comprehensive Toxicology DOI: 10.1016/b978-0-08-046884-6.01112-x sha: doc_id: 347298 cord_uid: 7kqrl3rv file: cache/cord-351489-tzmev77c.json key: cord-351489-tzmev77c authors: Yuan, Shuofeng; Chan, Chris Chun-Yiu; Chik, Kenn Ka-Heng; Tsang, Jessica Oi-Ling; Liang, Ronghui; Cao, Jianli; Tang, Kaiming; Cai, Jian-Piao; Ye, Zi-Wei; Yin, Feifei; To, Kelvin Kai-Wang; Chu, Hin; Jin, Dong-Yan; Hung, Ivan Fan-Ngai; Yuen, Kwok-Yung; Chan, Jasper Fuk-Woo title: Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) date: 2020-06-10 journal: Viruses DOI: 10.3390/v12060628 sha: doc_id: 351489 cord_uid: tzmev77c file: cache/cord-346212-mcnr7bcp.json key: cord-346212-mcnr7bcp authors: Bonzano, Chiara; Borroni, Davide; Lancia, Andrea; Bonzano, Elisabetta title: Doxycycline: From Ocular Rosacea to COVID-19 Anosmia. New Insight Into the Coronavirus Outbreak date: 2020-05-08 journal: Front Med (Lausanne) DOI: 10.3389/fmed.2020.00200 sha: doc_id: 346212 cord_uid: mcnr7bcp file: cache/cord-347460-9vechh4x.json key: cord-347460-9vechh4x authors: Chang, Feng-Yee; Chen, Hsiang-Cheng; Chen, Pei-Jer; Ho, Mei-Shang; Hsieh, Shie-Liang; Lin, Jung-Chung; Liu, Fu-Tong; Sytwu, Huey-Kang title: Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) date: 2020-06-04 journal: J Biomed Sci DOI: 10.1186/s12929-020-00663-w sha: doc_id: 347460 cord_uid: 9vechh4x file: cache/cord-354762-3a3a3ku9.json key: cord-354762-3a3a3ku9 authors: Afsar, Cigdem Usul; Afsar, Selim title: SARS-CoV-2 (COVID-19): INTERFERON-EPSILON MAY BE RESPONSIBLE OF DECREASED MORTALITY IN FEMALES date: 2020-06-02 journal: J Reprod Immunol DOI: 10.1016/j.jri.2020.103154 sha: doc_id: 354762 cord_uid: 3a3a3ku9 file: cache/cord-351845-bli3qm8w.json key: cord-351845-bli3qm8w authors: Prasad, Kartikay; Khatoon, Fatima; Rashid, Summya; Ali, Nemat; AlAsmari, Abdullah F.; Ahmed, Mohammad Z.; Alqahtani, Ali S.; Alqahtani, Mohammed S.; Kumar, Vijay title: Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective date: 2020-06-26 journal: Int J Biol Macromol DOI: 10.1016/j.ijbiomac.2020.06.228 sha: doc_id: 351845 cord_uid: bli3qm8w file: cache/cord-355839-o0m71kvw.json key: cord-355839-o0m71kvw authors: Sedeyn, Koen; Schepens, Bert; Saelens, Xavier title: Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses date: 2019-10-17 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1007984 sha: doc_id: 355839 cord_uid: o0m71kvw file: cache/cord-356094-sbtigcfr.json key: cord-356094-sbtigcfr authors: Chen, Huijie; Muhammad, Ishfaq; Zhang, Yue; Ren, Yudong; Zhang, Ruili; Huang, Xiaodan; Diao, Lei; Liu, Haixin; Li, Xunliang; Sun, Xiaoqi; Abbas, Ghulam; Li, Guangxing title: Antiviral Activity Against Infectious Bronchitis Virus and Bioactive Components of Hypericum perforatum L. date: 2019-10-29 journal: Front Pharmacol DOI: 10.3389/fphar.2019.01272 sha: doc_id: 356094 cord_uid: sbtigcfr file: cache/cord-349647-cfjrwt44.json key: cord-349647-cfjrwt44 authors: Girkin, Jason; Maltby, Steven; Singanayagam, Aran; Bartlett, Nathan; Mallia, Patrick title: Chapter 8 In vivo experimental models of infection and disease date: 2019-12-31 journal: Rhinovirus Infections DOI: 10.1016/b978-0-12-816417-4.00008-1 sha: doc_id: 349647 cord_uid: cfjrwt44 file: cache/cord-351520-c5fi2uoh.json key: cord-351520-c5fi2uoh authors: Zhong, Bo; Wang, Yan-Yi; Shu, Hong-Bing title: Regulation of virus-triggered type I interferon signaling by cellular and viral proteins date: 2010-02-01 journal: Front Biol (Beijing) DOI: 10.1007/s11515-010-0013-x sha: doc_id: 351520 cord_uid: c5fi2uoh file: cache/cord-355671-t890eixt.json key: cord-355671-t890eixt authors: Medina, Gisselle N.; Azzinaro, Paul; Ramirez-Medina, Elizabeth; Gutkoska, Joseph; Fang, Ying; Diaz-San Segundo, Fayna; de los Santos, Teresa title: Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo date: 2020-06-16 journal: J Virol DOI: 10.1128/jvi.00341-20 sha: doc_id: 355671 cord_uid: t890eixt file: cache/cord-351532-2yd4wg9v.json key: cord-351532-2yd4wg9v authors: Huang, Yin-Qiu; Tang, Sheng-Quan; Xu, Xiao-Lei; Zeng, Yan-Ming; He, Xiao-Qing; Li, Yao; Harypursat, Vijay; Lu, Yan-Qiu; Wan, Yan; Zhang, Lu; Sun, Qiang-Zhong; Sun, Nan-Nan; Wang, Gui-Xue; Yang, Zhong-Ping; Chen, Yao-Kai title: No Statistically Apparent Difference in Antiviral Effectiveness Observed Among Ribavirin Plus Interferon-Alpha, Lopinavir/Ritonavir Plus Interferon-Alpha, and Ribavirin Plus Lopinavir/Ritonavir Plus Interferon-Alpha in Patients With Mild to Moderate Coronavirus Disease 2019: Results of a Randomized, Open-Labeled Prospective Study date: 2020-07-14 journal: Front Pharmacol DOI: 10.3389/fphar.2020.01071 sha: doc_id: 351532 cord_uid: 2yd4wg9v file: cache/cord-354620-xf6glr2h.json key: cord-354620-xf6glr2h authors: Tian, Bin; Cai, Dongjie; He, Tianqiong; Deng, Liyao; Wu, Liping; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Yang, Qiao; Wu, Ying; Zhao, Xinxin; Chen, Shun; Zhang, Shaqiu; Huang, Juan; Ou, Xumin; Mao, Sai; Yu, Yanling; Zhang, Ling; Liu, Yunya; Cheng, Anchun title: Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus date: 2020-01-28 journal: Front Immunol DOI: 10.3389/fimmu.2019.03131 sha: doc_id: 354620 cord_uid: xf6glr2h file: cache/cord-353826-owoec2ud.json key: cord-353826-owoec2ud authors: Graham, Simon P.; McLean, Rebecca K.; Spencer, Alexandra J.; Belij-Rammerstorfer, Sandra; Wright, Daniel; Ulaszewska, Marta; Edwards, Jane C.; Hayes, Jack W. P.; Martini, Veronica; Thakur, Nazia; Conceicao, Carina; Dietrich, Isabelle; Shelton, Holly; Waters, Ryan; Ludi, Anna; Wilsden, Ginette; Browning, Clare; Bialy, Dagmara; Bhat, Sushant; Stevenson-Leggett, Phoebe; Hollinghurst, Philippa; Gilbride, Ciaran; Pulido, David; Moffat, Katy; Sharpe, Hannah; Allen, Elizabeth; Mioulet, Valerie; Chiu, Chris; Newman, Joseph; Asfor, Amin S.; Burman, Alison; Crossley, Sylvia; Huo, Jiandong; Owens, Raymond J.; Carroll, Miles; Hammond, John A.; Tchilian, Elma; Bailey, Dalan; Charleston, Bryan; Gilbert, Sarah C.; Tuthill, Tobias J.; Lambe, Teresa title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-07-27 journal: NPJ Vaccines DOI: 10.1038/s41541-020-00221-3 sha: doc_id: 353826 cord_uid: owoec2ud file: cache/cord-354000-jxqskt4k.json key: cord-354000-jxqskt4k authors: Warren, Cody J.; Griffin, Laura M.; Little, Alexander S.; Huang, I-Chueh; Farzan, Michael; Pyeon, Dohun title: The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date: 2014-05-14 journal: PLoS One DOI: 10.1371/journal.pone.0096579 sha: doc_id: 354000 cord_uid: jxqskt4k file: cache/cord-356197-js7l86fh.json key: cord-356197-js7l86fh authors: Zhou, Ping; Zhai, Shanli; Zhou, Xiang; Lin, Ping; Jiang, Tengfei; Hu, Xueying; Jiang, Yunbo; Wu, Bin; Zhang, Qingde; Xu, Xuewen; Li, Jin-ping; Liu, Bang title: Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo date: 2011-08-07 journal: Int J Biol Sci DOI: nan sha: doc_id: 356197 cord_uid: js7l86fh Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-ifn-cord parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 29773 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28038 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28744 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28845 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28921 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 29061 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 29155 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 29816 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 29824 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30601 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28113 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28151 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28771 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30813 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 29342 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30138 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 27823 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 27830 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28975 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 29158 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31126 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 29333 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 29491 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30755 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28431 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30169 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 28322 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30756 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31191 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30055 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31746 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30207 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30562 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30913 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 32716 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31385 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30265 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30777 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31910 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35107 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31834 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31540 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 32669 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 30123 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 32882 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34455 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34874 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33455 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-003855-so8xl199 author: Ebert, Gregor title: Virology Downunder, a meeting commentary from the 2019 Lorne Infection and Immunity Conference, Australia date: 2019-09-02 pages: extension: .txt txt: ./txt/cord-003855-so8xl199.txt cache: ./cache/cord-003855-so8xl199.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003855-so8xl199.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33749 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34575 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35293 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34536 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42164 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43162 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-001808-47496o0e author: Bayat, Ahmad title: Anti-cytokine autoantibodies in postherpetic neuralgia date: 2015-10-20 pages: extension: .txt txt: ./txt/cord-001808-47496o0e.txt cache: ./cache/cord-001808-47496o0e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001808-47496o0e.txt' === file2bib.sh === id: cord-000554-p4ufea6x author: Gao, Wei title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus date: 2012-01-18 pages: extension: .txt txt: ./txt/cord-000554-p4ufea6x.txt cache: ./cache/cord-000554-p4ufea6x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000554-p4ufea6x.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-004685-qote5nx2 author: Vassão, R. C. title: A genetic analysis of macrophage activation and specific antibodies in relation to the resistance of heterogeneous mouse populations to MHV3 infection date: 1994 pages: extension: .txt txt: ./txt/cord-004685-qote5nx2.txt cache: ./cache/cord-004685-qote5nx2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004685-qote5nx2.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37825 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43212 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43208 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43439 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-000725-rafwlw0t author: Hindinger, Claudia title: IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date: 2012-07-27 pages: extension: .txt txt: ./txt/cord-000725-rafwlw0t.txt cache: ./cache/cord-000725-rafwlw0t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000725-rafwlw0t.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 32820 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-008761-b36x05fn author: Billiau, A. title: The interferon system as a basis for antiviral therapy or prophylaxis date: 2012-02-26 pages: extension: .txt txt: ./txt/cord-008761-b36x05fn.txt cache: ./cache/cord-008761-b36x05fn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-008761-b36x05fn.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38111 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-000409-lpf9lpky author: Chen, Yongwen title: Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection date: 2011-07-07 pages: extension: .txt txt: ./txt/cord-000409-lpf9lpky.txt cache: ./cache/cord-000409-lpf9lpky.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000409-lpf9lpky.txt' === file2bib.sh === id: cord-008821-rxzgfk1k author: A. Lucchiari, Maria title: In vivo depletion of interferon-gamma leads to susceptibility of A/J mice to mouse hepatitis virus 3 infection date: 2011-11-02 pages: extension: .txt txt: ./txt/cord-008821-rxzgfk1k.txt cache: ./cache/cord-008821-rxzgfk1k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-008821-rxzgfk1k.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37773 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-000478-88wo4xen author: Gowen, Brian B. title: Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection date: 2011-10-24 pages: extension: .txt txt: ./txt/cord-000478-88wo4xen.txt cache: ./cache/cord-000478-88wo4xen.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000478-88wo4xen.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39446 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 44600 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 40460 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39472 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39540 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-005664-n4xv247l author: Plötz, Frans B. title: Mechanical ventilation alters the immune response in children without lung pathology date: 2002-01-15 pages: extension: .txt txt: ./txt/cord-005664-n4xv247l.txt cache: ./cache/cord-005664-n4xv247l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-005664-n4xv247l.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38618 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 38296 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 40759 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-001546-ndz3oarf author: Ayithan, Natarajan title: Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date: 2015-02-26 pages: extension: .txt txt: ./txt/cord-001546-ndz3oarf.txt cache: ./cache/cord-001546-ndz3oarf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001546-ndz3oarf.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 39653 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-007664-c5snhymz author: Mauerhoff, Thekla title: Differential expression and regulation of major histocompatibility complex (MHC) products in neural and glial cells of the human fetal brain date: 2002-11-13 pages: extension: .txt txt: ./txt/cord-007664-c5snhymz.txt cache: ./cache/cord-007664-c5snhymz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007664-c5snhymz.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42129 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42123 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42313 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43107 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-000125-uvf5qzfd author: Kenworthy, Rachael title: Short-hairpin RNAs delivered by lentiviral vector transduction trigger RIG-I-mediated IFN activation date: 2009-09-03 pages: extension: .txt txt: ./txt/cord-000125-uvf5qzfd.txt cache: ./cache/cord-000125-uvf5qzfd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000125-uvf5qzfd.txt' /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-007646-yh8zi1ee author: Weiss, R.C. title: Effect of recombinant human interferon-alpha in vitro and in vivo on mitogen-induced lymphocyte blastogenesis in cats() date: 2002-11-12 pages: extension: .txt txt: ./txt/cord-007646-yh8zi1ee.txt cache: ./cache/cord-007646-yh8zi1ee.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007646-yh8zi1ee.txt' === file2bib.sh === id: cord-023585-n3lr9z3u author: Phillpotts, Robert title: Interferon prophylaxis of the common cold date: 2003-01-06 pages: extension: .txt txt: ./txt/cord-023585-n3lr9z3u.txt cache: ./cache/cord-023585-n3lr9z3u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023585-n3lr9z3u.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 40801 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-001515-x11t9pbv author: Kosinska, Anna D. title: Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck date: 2014-12-23 pages: extension: .txt txt: ./txt/cord-001515-x11t9pbv.txt cache: ./cache/cord-001515-x11t9pbv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001515-x11t9pbv.txt' === file2bib.sh === id: cord-004341-co9s26x1 author: Thukral, Akanksha title: A single dose polyanhydride-based nanovaccine against paratuberculosis infection date: 2020-02-14 pages: extension: .txt txt: ./txt/cord-004341-co9s26x1.txt cache: ./cache/cord-004341-co9s26x1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004341-co9s26x1.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 42221 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-007013-tlvgyzft author: Chan, Kok Fei title: Investigating Viral Interference Between Influenza A Virus and Human Respiratory Syncytial Virus in a Ferret Model of Infection date: 2018-08-01 pages: extension: .txt txt: ./txt/cord-007013-tlvgyzft.txt cache: ./cache/cord-007013-tlvgyzft.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-007013-tlvgyzft.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-001848-idmj2d7p author: Onabajo, Olusegun O. title: Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells date: 2015-11-01 pages: extension: .txt txt: ./txt/cord-001848-idmj2d7p.txt cache: ./cache/cord-001848-idmj2d7p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001848-idmj2d7p.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35250 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 48967 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-003514-yyzbv7ys author: Arslan, Mehboob title: Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken date: 2019-02-14 pages: extension: .txt txt: ./txt/cord-003514-yyzbv7ys.txt cache: ./cache/cord-003514-yyzbv7ys.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003514-yyzbv7ys.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 49388 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-034467-jh9msz1c author: Olagoke, Olusola title: Koalas vaccinated against Koala retrovirus respond by producing increased levels of interferon-gamma date: 2020-10-31 pages: extension: .txt txt: ./txt/cord-034467-jh9msz1c.txt cache: ./cache/cord-034467-jh9msz1c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-034467-jh9msz1c.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50325 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51029 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51050 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-000660-tsvzg0ax author: Fensterl, Volker title: Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis date: 2012-05-17 pages: extension: .txt txt: ./txt/cord-000660-tsvzg0ax.txt cache: ./cache/cord-000660-tsvzg0ax.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000660-tsvzg0ax.txt' === file2bib.sh === id: cord-252950-eiphxwmn author: Trouillet-Assant, Sophie title: Type I IFN immunoprofiling in COVID-19 patients date: 2020-04-29 pages: extension: .txt txt: ./txt/cord-252950-eiphxwmn.txt cache: ./cache/cord-252950-eiphxwmn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252950-eiphxwmn.txt' === file2bib.sh === id: cord-012497-n5pu1yeu author: Rogers, Meredith C. title: STAT2 Limits Host Species Specificity of Human Metapneumovirus date: 2020-07-04 pages: extension: .txt txt: ./txt/cord-012497-n5pu1yeu.txt cache: ./cache/cord-012497-n5pu1yeu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-012497-n5pu1yeu.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51268 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 50591 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51637 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52460 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 84. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51817 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-011436-ud35mf5l author: Li, Yingying title: Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation date: 2020-04-06 pages: extension: .txt txt: ./txt/cord-011436-ud35mf5l.txt cache: ./cache/cord-011436-ud35mf5l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-011436-ud35mf5l.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31787 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51570 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51804 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52197 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52463 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 83. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 82. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53010 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-007796-zggk0x2q author: Lindemans, Caroline A. title: The Immune Response to Viral Lower Respiratory Tract Infection date: 2005 pages: extension: .txt txt: ./txt/cord-007796-zggk0x2q.txt cache: ./cache/cord-007796-zggk0x2q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007796-zggk0x2q.txt' === file2bib.sh === id: cord-013481-3zwq67do author: Guo, Kejun title: Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-013481-3zwq67do.txt cache: ./cache/cord-013481-3zwq67do.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-013481-3zwq67do.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52716 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-048489-ajafw966 author: Bozza, Fernando A title: Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity date: 2008-06-25 pages: extension: .txt txt: ./txt/cord-048489-ajafw966.txt cache: ./cache/cord-048489-ajafw966.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-048489-ajafw966.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51767 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 53844 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54835 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56082 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55414 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55819 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-017785-zwnkrs23 author: Baker, Michelle L. title: Mammalia: Chiroptera: Immunology of Bats date: 2018-03-10 pages: extension: .txt txt: ./txt/cord-017785-zwnkrs23.txt cache: ./cache/cord-017785-zwnkrs23.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017785-zwnkrs23.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 52821 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54022 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 54319 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-021872-rhi7hi9m author: Wilkes, Rebecca P. title: Update on Antiviral Therapies date: 2015-12-04 pages: extension: .txt txt: ./txt/cord-021872-rhi7hi9m.txt cache: ./cache/cord-021872-rhi7hi9m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-021872-rhi7hi9m.txt' === file2bib.sh === id: cord-025181-eg108wcd author: Zheng, Zhihang title: Establishment of Murine Infection Models with Biological Clones of Dengue Viruses Derived from a Single Clinical Viral Isolate date: 2020-05-25 pages: extension: .txt txt: ./txt/cord-025181-eg108wcd.txt cache: ./cache/cord-025181-eg108wcd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-025181-eg108wcd.txt' /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-002630-5616n73p author: Dargahi, Narges title: Multiple Sclerosis: Immunopathology and Treatment Update date: 2017-07-07 pages: extension: .txt txt: ./txt/cord-002630-5616n73p.txt cache: ./cache/cord-002630-5616n73p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002630-5616n73p.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-255709-tm3we5sd author: Mossel, Eric C. title: Synergistic Inhibition of Sars-Coronavirus Replication by Type I and Type II IFN date: 2006 pages: extension: .txt txt: ./txt/cord-255709-tm3we5sd.txt cache: ./cache/cord-255709-tm3we5sd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255709-tm3we5sd.txt' === file2bib.sh === id: cord-028945-p3hhd5ed author: Şahar, Esra Atalay title: Development of a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V and determination of its protective efficacy against acute toxoplasmosis date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-028945-p3hhd5ed.txt cache: ./cache/cord-028945-p3hhd5ed.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-028945-p3hhd5ed.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 81. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 84. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57783 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 57566 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59017 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33196 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58819 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58126 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 83. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 84. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58931 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58638 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59392 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 83. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-256293-5lpe8hg2 author: Kageyama, Y. title: Jinhua Qinggan granule, a Chinese herbal medicine against COVID-19, induces rapid changes in the plasma levels of IL-6 and IFN-γ date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-256293-5lpe8hg2.txt cache: ./cache/cord-256293-5lpe8hg2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-256293-5lpe8hg2.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-016343-wc3i54fc author: Frese, Michael title: Interferon-Induced Effector Proteins and Hepatitis C Virus Replication date: 2008 pages: extension: .txt txt: ./txt/cord-016343-wc3i54fc.txt cache: ./cache/cord-016343-wc3i54fc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016343-wc3i54fc.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-029488-l11ufs6k author: Tomita, Kengo title: Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-029488-l11ufs6k.txt cache: ./cache/cord-029488-l11ufs6k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-029488-l11ufs6k.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-252528-rgnhfcbx author: Du, Fenghe title: COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-252528-rgnhfcbx.txt cache: ./cache/cord-252528-rgnhfcbx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252528-rgnhfcbx.txt' /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59300 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60375 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60158 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60603 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60691 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60786 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60780 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60284 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 51144 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-255997-oer5lxxr author: Onodi, Fanny title: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-255997-oer5lxxr.txt cache: ./cache/cord-255997-oer5lxxr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255997-oer5lxxr.txt' === file2bib.sh === id: cord-023388-btbf6wkg author: Hoffmann, H. J. title: Decrease in Fine T‐cell Subset ratio MT2/MT1 During Steroid Reduction of Asthmatic Patients date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023388-btbf6wkg.txt cache: ./cache/cord-023388-btbf6wkg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023388-btbf6wkg.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61129 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63551 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-005953-5z89yeb6 author: nan title: Abstracts des 114. Internistenkongresses 2008 date: 2008 pages: extension: .txt txt: ./txt/cord-005953-5z89yeb6.txt cache: ./cache/cord-005953-5z89yeb6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-005953-5z89yeb6.txt' === file2bib.sh === id: cord-007696-83v9yfa6 author: Zisman, David A. title: Pulmonary Fibrosis date: 2005 pages: extension: .txt txt: ./txt/cord-007696-83v9yfa6.txt cache: ./cache/cord-007696-83v9yfa6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-007696-83v9yfa6.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63311 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63860 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-263200-ntq1f4ix author: Mao, He-Ting title: HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex date: 2016-05-21 pages: extension: .txt txt: ./txt/cord-263200-ntq1f4ix.txt cache: ./cache/cord-263200-ntq1f4ix.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263200-ntq1f4ix.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63532 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-258691-cd83w9o6 author: Whitman, Lucia title: IFN-γ-mediated suppression of coronavirus replication in glial-committed progenitor cells date: 2009-02-01 pages: extension: .txt txt: ./txt/cord-258691-cd83w9o6.txt cache: ./cache/cord-258691-cd83w9o6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-258691-cd83w9o6.txt' === file2bib.sh === id: cord-022631-s4n24xij author: Jonsson, M. V. title: Germinal Centres in Primary Sjögren's Syndrome Indicate a Certain Clinical Immunological Phenotype date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-022631-s4n24xij.txt cache: ./cache/cord-022631-s4n24xij.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-022631-s4n24xij.txt' === file2bib.sh === id: cord-254492-42d77vxf author: Heaton, Steven M. title: Ubiquitin in the activation and attenuation of innate antiviral immunity date: 2016-01-11 pages: extension: .txt txt: ./txt/cord-254492-42d77vxf.txt cache: ./cache/cord-254492-42d77vxf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-254492-42d77vxf.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65664 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64251 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65716 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-252568-b8sbvy0g author: Marques Neto, Lázaro Moreira title: Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development date: 2017-03-08 pages: extension: .txt txt: ./txt/cord-252568-b8sbvy0g.txt cache: ./cache/cord-252568-b8sbvy0g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252568-b8sbvy0g.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65681 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-273050-reez33md author: Wang, Zhenling title: Type I IFN deficiency: an immunological characteristic of severe COVID-19 patients date: 2020-09-14 pages: extension: .txt txt: ./txt/cord-273050-reez33md.txt cache: ./cache/cord-273050-reez33md.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-273050-reez33md.txt' === file2bib.sh === id: cord-023391-bq5w3jk9 author: Utermöhlen, O. title: Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023391-bq5w3jk9.txt cache: ./cache/cord-023391-bq5w3jk9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023391-bq5w3jk9.txt' === file2bib.sh === id: cord-261380-xms5su6w author: Rahmani, Hamid title: Interferon β-1b in treatment of severe COVID-19: a randomized clinical trial date: 2020-08-24 pages: extension: .txt txt: ./txt/cord-261380-xms5su6w.txt cache: ./cache/cord-261380-xms5su6w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-261380-xms5su6w.txt' === file2bib.sh === id: cord-023387-tyeh14wz author: Hvas, C. L. title: Probiotic Bacteria Induce Regulatory Cytokine Production via Dendritic Cells date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023387-tyeh14wz.txt cache: ./cache/cord-023387-tyeh14wz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023387-tyeh14wz.txt' === file2bib.sh === id: cord-258286-lodjcj8c author: Zhang, Xuming title: Expression of Interferon-γ by a Coronavirus Defective-Interfering RNA Vector and Its Effect on Viral Replication, Spread, and Pathogenicity date: 1997-07-07 pages: extension: .txt txt: ./txt/cord-258286-lodjcj8c.txt cache: ./cache/cord-258286-lodjcj8c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258286-lodjcj8c.txt' === file2bib.sh === id: cord-274816-6xpma224 author: Onal, Merih title: Can secondary lymphoid organs exert a favorable effect on the mild course of COVID-19 in children? date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-274816-6xpma224.txt cache: ./cache/cord-274816-6xpma224.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-274816-6xpma224.txt' === file2bib.sh === id: cord-276350-lcl9jn35 author: Acharya, Dhiraj title: Dysregulation of type I interferon responses in COVID-19 date: 2020-05-26 pages: extension: .txt txt: ./txt/cord-276350-lcl9jn35.txt cache: ./cache/cord-276350-lcl9jn35.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-276350-lcl9jn35.txt' === file2bib.sh === id: cord-270498-hh6h50t2 author: Tseng, Chin-Kai title: Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells date: 2017-09-19 pages: extension: .txt txt: ./txt/cord-270498-hh6h50t2.txt cache: ./cache/cord-270498-hh6h50t2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-270498-hh6h50t2.txt' === file2bib.sh === id: cord-001397-nrq4ncdf author: Mlera, Luwanika title: The role of viral persistence in flavivirus biology date: 2014-05-12 pages: extension: .txt txt: ./txt/cord-001397-nrq4ncdf.txt cache: ./cache/cord-001397-nrq4ncdf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001397-nrq4ncdf.txt' === file2bib.sh === id: cord-270534-ebkwv4zo author: Bodmer, Bianca S. title: Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model date: 2018-06-11 pages: extension: .txt txt: ./txt/cord-270534-ebkwv4zo.txt cache: ./cache/cord-270534-ebkwv4zo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270534-ebkwv4zo.txt' === file2bib.sh === id: cord-023033-tgt69ir6 author: nan title: Poster Session (pp. 78A–178A) date: 2006-02-10 pages: extension: .txt txt: ./txt/cord-023033-tgt69ir6.txt cache: ./cache/cord-023033-tgt69ir6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023033-tgt69ir6.txt' === file2bib.sh === id: cord-023443-pvz7dll9 author: nan title: Abstracts for the Scandinavian Society for Immunology 35th Annual Meeting and 20th Summer School date: 2004-06-02 pages: extension: .txt txt: ./txt/cord-023443-pvz7dll9.txt cache: ./cache/cord-023443-pvz7dll9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023443-pvz7dll9.txt' === file2bib.sh === id: cord-023392-axd0901z author: Hansen, T. K. title: Association between Mannose‐Binding Lectin and Vascular Complications in Type 1 Diabetes date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023392-axd0901z.txt cache: ./cache/cord-023392-axd0901z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023392-axd0901z.txt' === file2bib.sh === id: cord-275643-lbikoyo3 author: Beidas, Meshal title: Effect of Human Coronavirus OC43 Structural and Accessory Proteins on the Transcriptional Activation of Antiviral Response Elements date: 2018-07-24 pages: extension: .txt txt: ./txt/cord-275643-lbikoyo3.txt cache: ./cache/cord-275643-lbikoyo3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275643-lbikoyo3.txt' === file2bib.sh === id: cord-255773-b4re5bky author: Zhang, Qingzhan title: Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1 date: 2016-01-14 pages: extension: .txt txt: ./txt/cord-255773-b4re5bky.txt cache: ./cache/cord-255773-b4re5bky.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-255773-b4re5bky.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66525 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66872 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65993 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-272237-gnno6elo author: Wang, Ziran title: A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids date: 2020-07-31 pages: extension: .txt txt: ./txt/cord-272237-gnno6elo.txt cache: ./cache/cord-272237-gnno6elo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-272237-gnno6elo.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67247 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-023394-ptfjxpo6 author: Isa, A. title: Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023394-ptfjxpo6.txt cache: ./cache/cord-023394-ptfjxpo6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023394-ptfjxpo6.txt' === file2bib.sh === id: cord-023410-eblcf902 author: Kollgaard, T. M. title: Clonally Expanded CD8(+) T cells in Allogeneic Bone Marrow Transplantation date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023410-eblcf902.txt cache: ./cache/cord-023410-eblcf902.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023410-eblcf902.txt' === file2bib.sh === id: cord-262673-j2ot35lt author: Ahmed-Hassan, Hanaa title: Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-262673-j2ot35lt.txt cache: ./cache/cord-262673-j2ot35lt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-262673-j2ot35lt.txt' === file2bib.sh === id: cord-271970-i35pic5o author: Boris, Bonaventure title: A genome-wide CRISPR/Cas9 knock-out screen identifies the DEAD box RNA helicase DDX42 as a broad antiviral inhibitor date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-271970-i35pic5o.txt cache: ./cache/cord-271970-i35pic5o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-271970-i35pic5o.txt' === file2bib.sh === id: cord-278577-bx86tq0y author: Mikola, Emilia title: Tonsillar cytokine expression between patients with tonsillar hypertrophy and recurrent tonsillitis date: 2018-05-22 pages: extension: .txt txt: ./txt/cord-278577-bx86tq0y.txt cache: ./cache/cord-278577-bx86tq0y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278577-bx86tq0y.txt' === file2bib.sh === id: cord-023419-lnmc6vv5 author: Steinhauer, C. title: High‐Throughput Proteomics on Antibody‐based Microarrays: the Importance of Probe and Surface Design date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023419-lnmc6vv5.txt cache: ./cache/cord-023419-lnmc6vv5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023419-lnmc6vv5.txt' === file2bib.sh === id: cord-256325-q70rky3r author: Stewart, Cameron R. title: A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease date: 2017-07-04 pages: extension: .txt txt: ./txt/cord-256325-q70rky3r.txt cache: ./cache/cord-256325-q70rky3r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-256325-q70rky3r.txt' === file2bib.sh === id: cord-273144-er6irjw3 author: Powell, Fiona title: Development of reagents to study the turkey's immune response: Cloning and characterisation of two turkey cytokines, interleukin (IL)-10 and IL-13 date: 2012-06-15 pages: extension: .txt txt: ./txt/cord-273144-er6irjw3.txt cache: ./cache/cord-273144-er6irjw3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-273144-er6irjw3.txt' === file2bib.sh === id: cord-023431-zjyrhlxn author: Sigmundsdóttir, H. title: Differential Effects of Interleukin‐12 and Interleukin‐10 on Superantigen‐Induced Expression of Cutaneous Lymphocyte‐Associated Antigen and αEβ7 Integrin (CD103) by CD8(+) T cells date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023431-zjyrhlxn.txt cache: ./cache/cord-023431-zjyrhlxn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023431-zjyrhlxn.txt' === file2bib.sh === id: cord-023421-1d1gf7az author: Sønder, S. U. S. title: Monitoring Patients Treated with Type 1 Interferons: Antiviral versus MxA Induction Assays date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023421-1d1gf7az.txt cache: ./cache/cord-023421-1d1gf7az.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023421-1d1gf7az.txt' === file2bib.sh === id: cord-023429-x52gbklw author: Ruseva, M. title: Mannan‐Binding Lectin Inhibits Humoural Responses date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023429-x52gbklw.txt cache: ./cache/cord-023429-x52gbklw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023429-x52gbklw.txt' === file2bib.sh === id: cord-279725-d82sj80v author: Ströher, Ute title: Severe Acute Respiratory Syndrome-Related Coronavirus Is Inhibited by Interferon-α date: 2004-04-01 pages: extension: .txt txt: ./txt/cord-279725-d82sj80v.txt cache: ./cache/cord-279725-d82sj80v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279725-d82sj80v.txt' === file2bib.sh === id: cord-271114-hv3gwvdi author: Allam, Gamal title: Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms date: 2015-04-22 pages: extension: .txt txt: ./txt/cord-271114-hv3gwvdi.txt cache: ./cache/cord-271114-hv3gwvdi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271114-hv3gwvdi.txt' === file2bib.sh === id: cord-268419-j90daoiq author: Resende, Lucilene Aparecida title: Cytokine and nitric oxide patterns in dogs immunized with LBSap vaccine, before and after experimental challenge with Leishmania chagasi plus saliva of Lutzomyia longipalpis date: 2013-12-06 pages: extension: .txt txt: ./txt/cord-268419-j90daoiq.txt cache: ./cache/cord-268419-j90daoiq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-268419-j90daoiq.txt' === file2bib.sh === id: cord-272695-wmzq4lkh author: Ahmed, Ahmed A. title: TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-272695-wmzq4lkh.txt cache: ./cache/cord-272695-wmzq4lkh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-272695-wmzq4lkh.txt' === file2bib.sh === id: cord-270380-1me7ugkg author: Wang, Xiaona title: Cloning, Prokaryotic Soluble Expression, and Analysis of Antiviral Activity of Two Novel Feline IFN-ω Proteins date: 2020-03-19 pages: extension: .txt txt: ./txt/cord-270380-1me7ugkg.txt cache: ./cache/cord-270380-1me7ugkg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-270380-1me7ugkg.txt' === file2bib.sh === id: cord-285744-jpw8hen9 author: Byeon, Jung Hye title: Comparison of cytokine responses in nasopharyngeal aspirates from children with viral lower respiratory tract infections date: 2009-01-13 pages: extension: .txt txt: ./txt/cord-285744-jpw8hen9.txt cache: ./cache/cord-285744-jpw8hen9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285744-jpw8hen9.txt' === file2bib.sh === id: cord-277487-jgbjxgh1 author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-277487-jgbjxgh1.txt cache: ./cache/cord-277487-jgbjxgh1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277487-jgbjxgh1.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67706 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-275413-e2rhioty author: Rowland, Raymond R.R. title: The interaction between PRRSV and the late gestation pig fetus date: 2010-09-09 pages: extension: .txt txt: ./txt/cord-275413-e2rhioty.txt cache: ./cache/cord-275413-e2rhioty.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-275413-e2rhioty.txt' === file2bib.sh === id: cord-261028-sxux2ujo author: Vatner, Ralph E. title: STING, DCs and the link between innate and adaptive tumor immunity date: 2017-12-20 pages: extension: .txt txt: ./txt/cord-261028-sxux2ujo.txt cache: ./cache/cord-261028-sxux2ujo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-261028-sxux2ujo.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67757 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68455 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-023438-g0k0vvdc author: Krog, J. title: The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells, with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023438-g0k0vvdc.txt cache: ./cache/cord-023438-g0k0vvdc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023438-g0k0vvdc.txt' === file2bib.sh === id: cord-023417-by18aczt author: Vilhelmsson, M. title: The Malassezia sympodialis Allergen Mala s 11 with Sequence Similarity to Manganese Superoxide Dismutase Induces Maturation and Production of Inflammatory Cytokines in Human Dendritic Cells date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023417-by18aczt.txt cache: ./cache/cord-023417-by18aczt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023417-by18aczt.txt' === file2bib.sh === id: cord-259669-fod4xkd7 author: Summerfield, Artur title: The porcine dendritic cell family date: 2008-06-06 pages: extension: .txt txt: ./txt/cord-259669-fod4xkd7.txt cache: ./cache/cord-259669-fod4xkd7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-259669-fod4xkd7.txt' === file2bib.sh === id: cord-023439-r04y1j22 author: Hedegaard, C. J. title: The Role of Immune Complexes Consisting of Myelin Basic Protein (MBP), Anti‐MBP Antibodies and Complement in Promoting CD4(+) T‐cell Responses to MBP in Health and Multiple Sclerosis date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023439-r04y1j22.txt cache: ./cache/cord-023439-r04y1j22.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023439-r04y1j22.txt' === file2bib.sh === id: cord-280005-i9fp5rys author: Wang, Mengmei title: Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide -- a Single-Center, Randomized, Controlled Clinical Trial date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-280005-i9fp5rys.txt cache: ./cache/cord-280005-i9fp5rys.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280005-i9fp5rys.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69086 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69513 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69174 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-285757-fiqx4tll author: Mäkelä, M. J. title: Lack of Induction by Rhinoviruses of Systemic Type I Interferon Production or Enhanced MxA Protein Expression During the Common Cold date: 1999 pages: extension: .txt txt: ./txt/cord-285757-fiqx4tll.txt cache: ./cache/cord-285757-fiqx4tll.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-285757-fiqx4tll.txt' === file2bib.sh === id: cord-278397-u33x4jaw author: Abe, Takayuki title: Negative Regulation of Cytosolic Sensing of DNA date: 2018-10-29 pages: extension: .txt txt: ./txt/cord-278397-u33x4jaw.txt cache: ./cache/cord-278397-u33x4jaw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278397-u33x4jaw.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69270 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69718 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69407 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-276166-b1e0bbrp author: Li, Shi-fang title: Interferon-omega: Current status in clinical applications date: 2017-10-12 pages: extension: .txt txt: ./txt/cord-276166-b1e0bbrp.txt cache: ./cache/cord-276166-b1e0bbrp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-276166-b1e0bbrp.txt' === file2bib.sh === id: cord-272117-erzpz3c0 author: Downey, Jeffrey title: Dissecting host cell death programs in the pathogenesis of influenza date: 2018-04-18 pages: extension: .txt txt: ./txt/cord-272117-erzpz3c0.txt cache: ./cache/cord-272117-erzpz3c0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272117-erzpz3c0.txt' === file2bib.sh === id: cord-279733-c0w9bw5u author: Lui, Pak-Yin title: Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 date: 2016-04-20 pages: extension: .txt txt: ./txt/cord-279733-c0w9bw5u.txt cache: ./cache/cord-279733-c0w9bw5u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-279733-c0w9bw5u.txt' === file2bib.sh === id: cord-297712-yy4g5npi author: Zhu, Xinyu title: Porcine deltacoronavirus nsp5 inhibits interferon-β production through the cleavage of NEMO date: 2016-12-13 pages: extension: .txt txt: ./txt/cord-297712-yy4g5npi.txt cache: ./cache/cord-297712-yy4g5npi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297712-yy4g5npi.txt' === file2bib.sh === id: cord-023306-3gdfo6vd author: nan title: TSANZ Oral Abstracts date: 2010-03-01 pages: extension: .txt txt: ./txt/cord-023306-3gdfo6vd.txt cache: ./cache/cord-023306-3gdfo6vd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023306-3gdfo6vd.txt' === file2bib.sh === id: cord-304330-egvdvvtx author: Damsky, William title: When interferon tiptoes through COVID-19: Pernio-like lesions and their prognostic implications during SARS-CoV-2 infection date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-304330-egvdvvtx.txt cache: ./cache/cord-304330-egvdvvtx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-304330-egvdvvtx.txt' === file2bib.sh === id: cord-280130-ewqe9edq author: Weber, Friedemann title: Viral suppression of the interferon system date: 2007-01-27 pages: extension: .txt txt: ./txt/cord-280130-ewqe9edq.txt cache: ./cache/cord-280130-ewqe9edq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280130-ewqe9edq.txt' === file2bib.sh === id: cord-253862-jl1zhg13 author: Khalaf, Khalil title: SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-253862-jl1zhg13.txt cache: ./cache/cord-253862-jl1zhg13.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-253862-jl1zhg13.txt' === file2bib.sh === id: cord-271250-ywb26cq6 author: Sarkar, Indranil title: Selection of adjuvants for vaccines targeting specific pathogens date: 2019-04-22 pages: extension: .txt txt: ./txt/cord-271250-ywb26cq6.txt cache: ./cache/cord-271250-ywb26cq6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-271250-ywb26cq6.txt' === file2bib.sh === id: cord-288017-f9b3t0ts author: Kabeerdoss, Jayakanthan title: Understanding immunopathological fallout of human coronavirus infections including COVID‐19: Will they cross the path of rheumatologists? date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-288017-f9b3t0ts.txt cache: ./cache/cord-288017-f9b3t0ts.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-288017-f9b3t0ts.txt' === file2bib.sh === id: cord-277409-q5wx313k author: Resende, Lucilene Aparecida title: Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge date: 2016-08-24 pages: extension: .txt txt: ./txt/cord-277409-q5wx313k.txt cache: ./cache/cord-277409-q5wx313k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-277409-q5wx313k.txt' === file2bib.sh === id: cord-279924-09uwhxs9 author: Plaisted, Warren C. title: T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells date: 2014-01-01 pages: extension: .txt txt: ./txt/cord-279924-09uwhxs9.txt cache: ./cache/cord-279924-09uwhxs9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279924-09uwhxs9.txt' === file2bib.sh === id: cord-278648-hkvurb2k author: Menachery, Vineet D. title: Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis date: 2017-11-15 pages: extension: .txt txt: ./txt/cord-278648-hkvurb2k.txt cache: ./cache/cord-278648-hkvurb2k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-278648-hkvurb2k.txt' === file2bib.sh === id: cord-286328-ap0wfjhq author: Lewis, Toby C. title: Nasal cytokine responses to natural colds in asthmatic children date: 2012-11-26 pages: extension: .txt txt: ./txt/cord-286328-ap0wfjhq.txt cache: ./cache/cord-286328-ap0wfjhq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-286328-ap0wfjhq.txt' === file2bib.sh === id: cord-286072-kgpvdb42 author: Sa Ribero, Margarida title: Interplay between SARS-CoV-2 and the type I interferon response date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-286072-kgpvdb42.txt cache: ./cache/cord-286072-kgpvdb42.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-286072-kgpvdb42.txt' === file2bib.sh === id: cord-290593-vhmi2559 author: Lannes, Nils title: Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses date: 2012-08-30 pages: extension: .txt txt: ./txt/cord-290593-vhmi2559.txt cache: ./cache/cord-290593-vhmi2559.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-290593-vhmi2559.txt' === file2bib.sh === id: cord-292289-amzzdh3t author: Mochizuki, M. title: Inhibitory effects of recombinant feline interferon on the replication of feline enteropathogenic viruses in vitro date: 1994-03-31 pages: extension: .txt txt: ./txt/cord-292289-amzzdh3t.txt cache: ./cache/cord-292289-amzzdh3t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292289-amzzdh3t.txt' === file2bib.sh === id: cord-296033-5zyoddl7 author: Hu, Xiaoliang title: Transmissible Gastroenteritis Virus Papain-Like Protease 1 Antagonizes Production of Interferon-β through Its Deubiquitinase Activity date: 2017-10-23 pages: extension: .txt txt: ./txt/cord-296033-5zyoddl7.txt cache: ./cache/cord-296033-5zyoddl7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296033-5zyoddl7.txt' === file2bib.sh === id: cord-265941-eff4le0g author: Eng, Vik Ven title: The diverse roles of RIP kinases in host-pathogen interactions date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-265941-eff4le0g.txt cache: ./cache/cord-265941-eff4le0g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-265941-eff4le0g.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71706 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-292593-apdyaujt author: Coulter-Mackie, Marion title: In vivo and in vitro models of demyelinating diseases XII. Persistence and expression of corona JHM vims functions in RN2-2 Schwannoma cells during latency date: 1985-10-31 pages: extension: .txt txt: ./txt/cord-292593-apdyaujt.txt cache: ./cache/cord-292593-apdyaujt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-292593-apdyaujt.txt' === file2bib.sh === id: cord-282947-3hgku2e4 author: Wong, Hui Hui title: Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3 date: 2017-12-30 pages: extension: .txt txt: ./txt/cord-282947-3hgku2e4.txt cache: ./cache/cord-282947-3hgku2e4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-282947-3hgku2e4.txt' === file2bib.sh === id: cord-296441-682uop9z author: Montoya, María title: Expression Dynamics of Innate Immunity in Influenza Virus-Infected Swine date: 2017-04-21 pages: extension: .txt txt: ./txt/cord-296441-682uop9z.txt cache: ./cache/cord-296441-682uop9z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296441-682uop9z.txt' === file2bib.sh === id: cord-287874-wl0wlxh6 author: Wang, Ling title: Quadruple therapy for asymptomatic COVID-19 infection patients date: 2020-05-03 pages: extension: .txt txt: ./txt/cord-287874-wl0wlxh6.txt cache: ./cache/cord-287874-wl0wlxh6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287874-wl0wlxh6.txt' === file2bib.sh === id: cord-283505-ousbar6c author: Horman, William S. J. title: The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-283505-ousbar6c.txt cache: ./cache/cord-283505-ousbar6c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-283505-ousbar6c.txt' === file2bib.sh === id: cord-303893-47lxq8pi author: Jalkanen, Juho title: Interferon beta-1a for COVID-19: critical importance of the administration route date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-303893-47lxq8pi.txt cache: ./cache/cord-303893-47lxq8pi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303893-47lxq8pi.txt' === file2bib.sh === id: cord-285148-bch7814v author: Singanayagam, Aran title: Viruses exacerbating chronic pulmonary disease: the role of immune modulation date: 2012-03-15 pages: extension: .txt txt: ./txt/cord-285148-bch7814v.txt cache: ./cache/cord-285148-bch7814v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285148-bch7814v.txt' === file2bib.sh === id: cord-299549-bjqwwzam author: Zhang, Lei title: Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis date: 2015-01-01 pages: extension: .txt txt: ./txt/cord-299549-bjqwwzam.txt cache: ./cache/cord-299549-bjqwwzam.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-299549-bjqwwzam.txt' === file2bib.sh === id: cord-290396-cy4y8vnt author: Kumar, Matam Vijay title: Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells date: 2004-07-01 pages: extension: .txt txt: ./txt/cord-290396-cy4y8vnt.txt cache: ./cache/cord-290396-cy4y8vnt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-290396-cy4y8vnt.txt' === file2bib.sh === id: cord-297776-k38jssr0 author: Volk, Aaron title: Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages date: 2020-05-18 pages: extension: .txt txt: ./txt/cord-297776-k38jssr0.txt cache: ./cache/cord-297776-k38jssr0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297776-k38jssr0.txt' === file2bib.sh === id: cord-295684-d3p9nbgq author: Lasfar, Ahmed title: Interferon Lambda: A New Sword in Cancer Immunotherapy date: 2011-12-06 pages: extension: .txt txt: ./txt/cord-295684-d3p9nbgq.txt cache: ./cache/cord-295684-d3p9nbgq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-295684-d3p9nbgq.txt' === file2bib.sh === id: cord-300319-9k8zseao author: Cinatl Jr., J. title: Infection of cultured intestinal epithelial cells with severe acute respiratory syndrome coronavirus date: 2004 pages: extension: .txt txt: ./txt/cord-300319-9k8zseao.txt cache: ./cache/cord-300319-9k8zseao.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-300319-9k8zseao.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72365 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-295781-b831y105 author: VanLeuven, James T. title: Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses date: 2017-06-02 pages: extension: .txt txt: ./txt/cord-295781-b831y105.txt cache: ./cache/cord-295781-b831y105.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-295781-b831y105.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72810 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72973 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72460 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-289101-ko1knslk author: Fu, Weihui title: An open-label, randomized trial of the combination of IFN-κ plus TFF2 with standard care in the treatment of patients with moderate COVID-19 date: 2020-09-20 pages: extension: .txt txt: ./txt/cord-289101-ko1knslk.txt cache: ./cache/cord-289101-ko1knslk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-289101-ko1knslk.txt' === file2bib.sh === id: cord-298259-r9rn0yyz author: Omatsu, Tsutomu title: Induction and sequencing of Rousette bat interferon α and β genes date: 2008-07-15 pages: extension: .txt txt: ./txt/cord-298259-r9rn0yyz.txt cache: ./cache/cord-298259-r9rn0yyz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298259-r9rn0yyz.txt' === file2bib.sh === id: cord-259748-x7dq1sy4 author: Wan, Dongshan title: Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-259748-x7dq1sy4.txt cache: ./cache/cord-259748-x7dq1sy4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-259748-x7dq1sy4.txt' === file2bib.sh === id: cord-265005-e6rpryrh author: Tomasello, Elena title: Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types date: 2014-10-30 pages: extension: .txt txt: ./txt/cord-265005-e6rpryrh.txt cache: ./cache/cord-265005-e6rpryrh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-265005-e6rpryrh.txt' === file2bib.sh === id: cord-304457-8g36h1bz author: Idelsis, E.-M. title: Effect and safety of combination of interferon alpha-2b and gamma or interferon alpha-2b for negativization of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial. date: 2020-08-01 pages: extension: .txt txt: ./txt/cord-304457-8g36h1bz.txt cache: ./cache/cord-304457-8g36h1bz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304457-8g36h1bz.txt' === file2bib.sh === id: cord-287018-g4y5kjju author: Konstantinova, P title: Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA date: 2006-05-18 pages: extension: .txt txt: ./txt/cord-287018-g4y5kjju.txt cache: ./cache/cord-287018-g4y5kjju.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287018-g4y5kjju.txt' === file2bib.sh === id: cord-299756-m0va36er author: Raaben, Matthijs title: Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo date: 2009-08-03 pages: extension: .txt txt: ./txt/cord-299756-m0va36er.txt cache: ./cache/cord-299756-m0va36er.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-299756-m0va36er.txt' === file2bib.sh === id: cord-299299-ov6bf1ff author: Janowicz, Anna title: Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8 date: 2015-03-11 pages: extension: .txt txt: ./txt/cord-299299-ov6bf1ff.txt cache: ./cache/cord-299299-ov6bf1ff.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-299299-ov6bf1ff.txt' === file2bib.sh === id: cord-311718-z64g8fce author: Chu, Yeonjeong title: Design, synthesis, and biological evaluation of N-arylpiperazine derivatives as interferon inducers date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-311718-z64g8fce.txt cache: ./cache/cord-311718-z64g8fce.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311718-z64g8fce.txt' === file2bib.sh === id: cord-299733-4mpz5l9e author: Mitchell, William M. title: Discordant Biological and Toxicological Species Responses to TLR3 Activation date: 2014-04-30 pages: extension: .txt txt: ./txt/cord-299733-4mpz5l9e.txt cache: ./cache/cord-299733-4mpz5l9e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-299733-4mpz5l9e.txt' === file2bib.sh === id: cord-294125-v2dr4hm0 author: Albert, Manuel title: ISG15, a Small Molecule with Huge Implications: Regulation of Mitochondrial Homeostasis date: 2018-11-13 pages: extension: .txt txt: ./txt/cord-294125-v2dr4hm0.txt cache: ./cache/cord-294125-v2dr4hm0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294125-v2dr4hm0.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73759 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74048 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 74814 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75089 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-305959-x061q8t7 author: Davoudi-Monfared, Effat title: A Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of Severe COVID-19 date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-305959-x061q8t7.txt cache: ./cache/cord-305959-x061q8t7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305959-x061q8t7.txt' === file2bib.sh === id: cord-310444-02dsqbeg author: Mahlakoiv, T. title: P136 Combined action of type I and type III IFN restricts initial replication of SARS-coronavirus in the lung but fails to inhibit systemic virus spread date: 2012-09-30 pages: extension: .txt txt: ./txt/cord-310444-02dsqbeg.txt cache: ./cache/cord-310444-02dsqbeg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-310444-02dsqbeg.txt' === file2bib.sh === id: cord-299949-kmn53e2z author: Schultz, Kimberly L.W. title: Immune Responses to Viruses in the CNS date: 2016-05-09 pages: extension: .txt txt: ./txt/cord-299949-kmn53e2z.txt cache: ./cache/cord-299949-kmn53e2z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-299949-kmn53e2z.txt' === file2bib.sh === id: cord-305315-0qt7eth0 author: Cao, Liyan title: Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-β production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway date: 2015-08-18 pages: extension: .txt txt: ./txt/cord-305315-0qt7eth0.txt cache: ./cache/cord-305315-0qt7eth0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305315-0qt7eth0.txt' === file2bib.sh === id: cord-300648-ixiam7qr author: Zhu, Xun title: IFITM3‐containing exosome as a novel mediator for anti‐viral response in dengue virus infection date: 2014-08-30 pages: extension: .txt txt: ./txt/cord-300648-ixiam7qr.txt cache: ./cache/cord-300648-ixiam7qr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-300648-ixiam7qr.txt' === file2bib.sh === id: cord-283096-qm7h4qui author: Jeon, Young Joo title: ISG15 and immune diseases date: 2010-02-12 pages: extension: .txt txt: ./txt/cord-283096-qm7h4qui.txt cache: ./cache/cord-283096-qm7h4qui.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-283096-qm7h4qui.txt' === file2bib.sh === id: cord-288238-36hiiw91 author: Keshavarz, Mohsen title: Metabolic host response and therapeutic approaches to influenza infection date: 2020-03-05 pages: extension: .txt txt: ./txt/cord-288238-36hiiw91.txt cache: ./cache/cord-288238-36hiiw91.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-288238-36hiiw91.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75322 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-279781-5ldpz9m9 author: Chen, Chi-Yuan title: Baculovirus as a gene delivery vector: Recent understandings of molecular alterations in transduced cells and latest applications date: 2011-04-28 pages: extension: .txt txt: ./txt/cord-279781-5ldpz9m9.txt cache: ./cache/cord-279781-5ldpz9m9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-279781-5ldpz9m9.txt' === file2bib.sh === id: cord-257220-fe2sacjj author: Butler, J. E. title: Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic date: 2014-07-01 pages: extension: .txt txt: ./txt/cord-257220-fe2sacjj.txt cache: ./cache/cord-257220-fe2sacjj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-257220-fe2sacjj.txt' === file2bib.sh === id: cord-303344-4aeu9n5v author: Honke, Nadine title: Multiple functions of USP18 date: 2016-11-03 pages: extension: .txt txt: ./txt/cord-303344-4aeu9n5v.txt cache: ./cache/cord-303344-4aeu9n5v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303344-4aeu9n5v.txt' === file2bib.sh === id: cord-305263-fgwf6wy3 author: Wang, Ben X. title: The yin and yang of viruses and interferons date: 2012-02-07 pages: extension: .txt txt: ./txt/cord-305263-fgwf6wy3.txt cache: ./cache/cord-305263-fgwf6wy3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305263-fgwf6wy3.txt' === file2bib.sh === id: cord-310469-v4p01rze author: Livonesi, Márcia Cristina title: In vitro and in vivo studies of the Interferon-alpha action on distinct Orthobunyavirus date: 2007-02-28 pages: extension: .txt txt: ./txt/cord-310469-v4p01rze.txt cache: ./cache/cord-310469-v4p01rze.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-310469-v4p01rze.txt' === file2bib.sh === id: cord-308298-5ntdb8yf author: Mair, Kerstin H title: Porcine CD8α(dim/-)NKp46(high) NK cells are in a highly activated state date: 2013-03-01 pages: extension: .txt txt: ./txt/cord-308298-5ntdb8yf.txt cache: ./cache/cord-308298-5ntdb8yf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-308298-5ntdb8yf.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75697 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33536 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-309428-qkjjxr6p author: Li, Liwei title: Host miR-26a suppresses replication of porcine reproductive and respiratory syndrome virus by upregulating type I interferons date: 2015-01-02 pages: extension: .txt txt: ./txt/cord-309428-qkjjxr6p.txt cache: ./cache/cord-309428-qkjjxr6p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309428-qkjjxr6p.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75924 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 76189 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-315328-8g40ukml author: Clementi, Nicola title: Interferon-β-1a Inhibition of Severe Acute Respiratory Syndrome–Coronavirus 2 In Vitro When Administered After Virus Infection date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-315328-8g40ukml.txt cache: ./cache/cord-315328-8g40ukml.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-315328-8g40ukml.txt' === file2bib.sh === id: cord-307333-n6jc0jy3 author: Selvaggi, Carla title: Interferon lambda 1–3 expression in infants hospitalized for RSV or HRV associated bronchiolitis date: 2014-01-02 pages: extension: .txt txt: ./txt/cord-307333-n6jc0jy3.txt cache: ./cache/cord-307333-n6jc0jy3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307333-n6jc0jy3.txt' === file2bib.sh === id: cord-306533-lvm11o4r author: Woo, Bean title: Regulatory interplay between deubiquitinating enzymes and cytokines date: 2019-06-08 pages: extension: .txt txt: ./txt/cord-306533-lvm11o4r.txt cache: ./cache/cord-306533-lvm11o4r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306533-lvm11o4r.txt' === file2bib.sh === id: cord-297790-tpjxt0w5 author: Mandl, Judith N. title: Going to Bat(s) for Studies of Disease Tolerance date: 2018-09-20 pages: extension: .txt txt: ./txt/cord-297790-tpjxt0w5.txt cache: ./cache/cord-297790-tpjxt0w5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-297790-tpjxt0w5.txt' === file2bib.sh === id: cord-302340-pw2xqhwa author: Feeley, Eric M. title: IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry date: 2011-10-27 pages: extension: .txt txt: ./txt/cord-302340-pw2xqhwa.txt cache: ./cache/cord-302340-pw2xqhwa.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-302340-pw2xqhwa.txt' === file2bib.sh === id: cord-314333-hkyiy1gm author: Nagata, Noriyo title: Mouse-Passaged Severe Acute Respiratory Syndrome-Associated Coronavirus Leads to Lethal Pulmonary Edema and Diffuse Alveolar Damage in Adult but Not Young Mice date: 2008-06-30 pages: extension: .txt txt: ./txt/cord-314333-hkyiy1gm.txt cache: ./cache/cord-314333-hkyiy1gm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-314333-hkyiy1gm.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 76819 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 76918 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-306424-gf0bglm0 author: Scutigliani, Enzo Maxim title: Interaction of the innate immune system with positive-strand RNA virus replication organelles date: 2017-06-27 pages: extension: .txt txt: ./txt/cord-306424-gf0bglm0.txt cache: ./cache/cord-306424-gf0bglm0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-306424-gf0bglm0.txt' === file2bib.sh === id: cord-309381-cb80ntxs author: Nogales, Aitor title: Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans date: 2019-09-30 pages: extension: .txt txt: ./txt/cord-309381-cb80ntxs.txt cache: ./cache/cord-309381-cb80ntxs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309381-cb80ntxs.txt' === file2bib.sh === id: cord-318339-j35w1vsw author: Stockman, Lauren J title: SARS: Systematic Review of Treatment Effects date: 2006-09-12 pages: extension: .txt txt: ./txt/cord-318339-j35w1vsw.txt cache: ./cache/cord-318339-j35w1vsw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318339-j35w1vsw.txt' === file2bib.sh === id: cord-302953-gr2kk9w4 author: Baxter, Victoria K. title: Interferon-Gamma Modulation of the Local T Cell Response to Alphavirus Encephalomyelitis date: 2020-01-16 pages: extension: .txt txt: ./txt/cord-302953-gr2kk9w4.txt cache: ./cache/cord-302953-gr2kk9w4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-302953-gr2kk9w4.txt' === file2bib.sh === id: cord-317333-unrd76bo author: Danesh, Ali title: Early gene expression events in ferrets in response to SARS coronavirus infection versus direct interferon-alpha2b stimulation date: 2011-01-05 pages: extension: .txt txt: ./txt/cord-317333-unrd76bo.txt cache: ./cache/cord-317333-unrd76bo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-317333-unrd76bo.txt' === file2bib.sh === id: cord-319779-n5w1f0rr author: Lee, Sang-Myeong title: Porcine reproductive and respiratory syndrome virus field isolates differ in in vitro interferon phenotypes date: 2004-12-08 pages: extension: .txt txt: ./txt/cord-319779-n5w1f0rr.txt cache: ./cache/cord-319779-n5w1f0rr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319779-n5w1f0rr.txt' === file2bib.sh === id: cord-317573-wp2wr3b5 author: Peng, Hui title: Human memory T cell responses to SARS-CoV E protein date: 2006-06-30 pages: extension: .txt txt: ./txt/cord-317573-wp2wr3b5.txt cache: ./cache/cord-317573-wp2wr3b5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317573-wp2wr3b5.txt' === file2bib.sh === id: cord-323713-bc00vths author: Volpi, Stefano title: Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome date: 2019-05-29 pages: extension: .txt txt: ./txt/cord-323713-bc00vths.txt cache: ./cache/cord-323713-bc00vths.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323713-bc00vths.txt' === file2bib.sh === id: cord-312955-gs65c3fy author: Schreiber, Gideon title: The Role of Type I Interferons in the Pathogenesis and Treatment of COVID-19 date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-312955-gs65c3fy.txt cache: ./cache/cord-312955-gs65c3fy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312955-gs65c3fy.txt' === file2bib.sh === id: cord-310861-9kb0b6rq author: Koo, Bonhan title: An isothermal, label-free, and rapid one-step RNA amplification/detection assay for diagnosis of respiratory viral infections date: 2017-04-15 pages: extension: .txt txt: ./txt/cord-310861-9kb0b6rq.txt cache: ./cache/cord-310861-9kb0b6rq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310861-9kb0b6rq.txt' === file2bib.sh === id: cord-312075-asbt0mcj author: Schulz, Katharina S. title: Viral Evasion Strategies in Type I IFN Signaling – A Summary of Recent Developments date: 2016-11-11 pages: extension: .txt txt: ./txt/cord-312075-asbt0mcj.txt cache: ./cache/cord-312075-asbt0mcj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312075-asbt0mcj.txt' === file2bib.sh === id: cord-317499-mxt7stat author: Saraya, Takeshi title: Epidemiology of virus-induced asthma exacerbations: with special reference to the role of human rhinovirus date: 2014-05-26 pages: extension: .txt txt: ./txt/cord-317499-mxt7stat.txt cache: ./cache/cord-317499-mxt7stat.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317499-mxt7stat.txt' === file2bib.sh === id: cord-318364-5bmdzgla author: Sun, Xinjuan title: Cytokine storm intervention in the early stages of COVID-19 pneumonia date: 2020-04-25 pages: extension: .txt txt: ./txt/cord-318364-5bmdzgla.txt cache: ./cache/cord-318364-5bmdzgla.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318364-5bmdzgla.txt' === file2bib.sh === id: cord-312386-88uwlmjx author: Kuchipudi, Suresh V. title: The Complex Role of STAT3 in Viral Infections date: 2015-06-25 pages: extension: .txt txt: ./txt/cord-312386-88uwlmjx.txt cache: ./cache/cord-312386-88uwlmjx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312386-88uwlmjx.txt' === file2bib.sh === id: cord-288960-v6l6o5va author: Li, Yang title: Regulating STING in health and disease date: 2017-06-07 pages: extension: .txt txt: ./txt/cord-288960-v6l6o5va.txt cache: ./cache/cord-288960-v6l6o5va.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-288960-v6l6o5va.txt' === file2bib.sh === id: cord-309619-glb2y82u author: Domingo, Pere title: The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19) date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-309619-glb2y82u.txt cache: ./cache/cord-309619-glb2y82u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309619-glb2y82u.txt' === file2bib.sh === id: cord-308932-pp8etmwq author: Baker, M. L. title: Antiviral Immune Responses of Bats: A Review date: 2012-08-01 pages: extension: .txt txt: ./txt/cord-308932-pp8etmwq.txt cache: ./cache/cord-308932-pp8etmwq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308932-pp8etmwq.txt' === file2bib.sh === id: cord-322683-wkrj6n1d author: Zhang, Pengfei title: Cellular Poly(C) Binding Protein 2 Interacts with porcine epidemic diarrhea virus Papain-Like Protease 1 and Supports Viral Replication date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-322683-wkrj6n1d.txt cache: ./cache/cord-322683-wkrj6n1d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-322683-wkrj6n1d.txt' === file2bib.sh === id: cord-311823-85wj08gr author: Katze, Michael G. title: Innate immune modulation by RNA viruses: emerging insights from functional genomics date: 2008 pages: extension: .txt txt: ./txt/cord-311823-85wj08gr.txt cache: ./cache/cord-311823-85wj08gr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311823-85wj08gr.txt' === file2bib.sh === id: cord-307598-p54p7enk author: Schlee, Martin title: Master sensors of pathogenic RNA – RIG-I like receptors date: 2013-07-01 pages: extension: .txt txt: ./txt/cord-307598-p54p7enk.txt cache: ./cache/cord-307598-p54p7enk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307598-p54p7enk.txt' === file2bib.sh === id: cord-321050-yabt72jf author: Tuttle, Kathryn D. title: JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-321050-yabt72jf.txt cache: ./cache/cord-321050-yabt72jf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321050-yabt72jf.txt' === file2bib.sh === id: cord-304553-gbwb7fqi author: Christopher, Mary E. title: Broad-Spectrum Drugs Against Viral Agents date: 2008-09-01 pages: extension: .txt txt: ./txt/cord-304553-gbwb7fqi.txt cache: ./cache/cord-304553-gbwb7fqi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-304553-gbwb7fqi.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 78339 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-310252-0cdqhrcw author: Seliger, Barbara title: Chapter 7 IFN Inducibility of Major Histocompatibility Antigens in Tumors date: 2008-12-03 pages: extension: .txt txt: ./txt/cord-310252-0cdqhrcw.txt cache: ./cache/cord-310252-0cdqhrcw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310252-0cdqhrcw.txt' === file2bib.sh === id: cord-303189-ktl4jw8v author: Coccia, Eliana M. title: Early IFN type I response: Learning from microbial evasion strategies date: 2015-03-31 pages: extension: .txt txt: ./txt/cord-303189-ktl4jw8v.txt cache: ./cache/cord-303189-ktl4jw8v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-303189-ktl4jw8v.txt' === file2bib.sh === id: cord-320338-jv76j6wx author: Lee, Kyungjin title: Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion date: 2017-12-15 pages: extension: .txt txt: ./txt/cord-320338-jv76j6wx.txt cache: ./cache/cord-320338-jv76j6wx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320338-jv76j6wx.txt' === file2bib.sh === id: cord-325989-nf6ouaq3 author: Es-Saad, Salwa title: Regulators of innate immunity as novel targets for panviral therapeutics date: 2012-09-24 pages: extension: .txt txt: ./txt/cord-325989-nf6ouaq3.txt cache: ./cache/cord-325989-nf6ouaq3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325989-nf6ouaq3.txt' === file2bib.sh === id: cord-315072-b28yikvj author: Giotis, Efstathios S. title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) date: 2016-08-05 pages: extension: .txt txt: ./txt/cord-315072-b28yikvj.txt cache: ./cache/cord-315072-b28yikvj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-315072-b28yikvj.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 80115 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-319501-a2x1hvkk author: Wong, Lok-Yin Roy title: A molecular arms race between host innate antiviral response and emerging human coronaviruses date: 2016-01-15 pages: extension: .txt txt: ./txt/cord-319501-a2x1hvkk.txt cache: ./cache/cord-319501-a2x1hvkk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319501-a2x1hvkk.txt' === file2bib.sh === id: cord-321992-lk2ao6m8 author: Annamalai, Thavamathi title: Age-dependent variation in innate immune responses to porcine epidemic diarrhea virus infection in suckling versus weaned pigs date: 2015-12-15 pages: extension: .txt txt: ./txt/cord-321992-lk2ao6m8.txt cache: ./cache/cord-321992-lk2ao6m8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321992-lk2ao6m8.txt' === file2bib.sh === id: cord-307813-elom30nx author: Yip, Tsz-Fung title: Advancements in Host-Based Interventions for Influenza Treatment date: 2018-07-10 pages: extension: .txt txt: ./txt/cord-307813-elom30nx.txt cache: ./cache/cord-307813-elom30nx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307813-elom30nx.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 77670 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-321947-qek9jy2c author: Lee, Su Jeen title: Evaluation of glycoprotein E subunit and live attenuated varicella‐zoster virus vaccines formulated with a single‐strand RNA‐based adjuvant date: 2020-03-13 pages: extension: .txt txt: ./txt/cord-321947-qek9jy2c.txt cache: ./cache/cord-321947-qek9jy2c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321947-qek9jy2c.txt' === file2bib.sh === id: cord-327685-fymfqvp3 author: Channappanavar, Rudragouda title: Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology date: 2017-05-02 pages: extension: .txt txt: ./txt/cord-327685-fymfqvp3.txt cache: ./cache/cord-327685-fymfqvp3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-327685-fymfqvp3.txt' === file2bib.sh === id: cord-323756-atnrw9ew author: Vabret, Nicolas title: Sensing Microbial RNA in the Cytosol date: 2013-12-25 pages: extension: .txt txt: ./txt/cord-323756-atnrw9ew.txt cache: ./cache/cord-323756-atnrw9ew.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323756-atnrw9ew.txt' === file2bib.sh === id: cord-326762-t89jtjmi author: Chen, Weiye title: Establishment of a stable CHO cell line with high level expression of recombinant porcine IFN-β date: 2011-06-30 pages: extension: .txt txt: ./txt/cord-326762-t89jtjmi.txt cache: ./cache/cord-326762-t89jtjmi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326762-t89jtjmi.txt' === file2bib.sh === id: cord-312001-8p7scli8 author: Majzoub, Karim title: The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans date: 2019-08-16 pages: extension: .txt txt: ./txt/cord-312001-8p7scli8.txt cache: ./cache/cord-312001-8p7scli8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312001-8p7scli8.txt' === file2bib.sh === id: cord-333600-k6ws97at author: Mihm, Sabine title: COVID-19: Possible Impact of the Genetic Background in IFNL Genes on Disease Outcomes date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-333600-k6ws97at.txt cache: ./cache/cord-333600-k6ws97at.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-333600-k6ws97at.txt' === file2bib.sh === id: cord-334510-37g8zxne author: Jartti, T. title: Distinct regulation of tonsillar immune response in virus infection date: 2014-03-29 pages: extension: .txt txt: ./txt/cord-334510-37g8zxne.txt cache: ./cache/cord-334510-37g8zxne.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-334510-37g8zxne.txt' === file2bib.sh === id: cord-333650-4towah1t author: Malmo, Jostein title: Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date: 2016-05-12 pages: extension: .txt txt: ./txt/cord-333650-4towah1t.txt cache: ./cache/cord-333650-4towah1t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333650-4towah1t.txt' === file2bib.sh === id: cord-315483-l6dm82pp author: Santhakumar, Diwakar title: Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses date: 2018-05-01 pages: extension: .txt txt: ./txt/cord-315483-l6dm82pp.txt cache: ./cache/cord-315483-l6dm82pp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315483-l6dm82pp.txt' === file2bib.sh === id: cord-338602-6n309bnp author: Gadotti, Ana Carolina title: IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-338602-6n309bnp.txt cache: ./cache/cord-338602-6n309bnp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338602-6n309bnp.txt' === file2bib.sh === id: cord-256998-or73in8m author: Nguyen, Khue G. title: Localized Interleukin-12 for Cancer Immunotherapy date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-256998-or73in8m.txt cache: ./cache/cord-256998-or73in8m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-256998-or73in8m.txt' === file2bib.sh === id: cord-333955-bnzbppof author: Biesold, Susanne E. title: Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum date: 2011-11-30 pages: extension: .txt txt: ./txt/cord-333955-bnzbppof.txt cache: ./cache/cord-333955-bnzbppof.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333955-bnzbppof.txt' === file2bib.sh === id: cord-342063-1si0qrrx author: Battesti, G. title: Negative tests for SARS‐CoV‐2 infection do not rule out its responsibility for chilblains date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-342063-1si0qrrx.txt cache: ./cache/cord-342063-1si0qrrx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342063-1si0qrrx.txt' === file2bib.sh === id: cord-315730-fzgxuak7 author: Penman, Sophie L. title: Safety perspectives on presently considered drugs for the treatment of COVID‐19 date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-315730-fzgxuak7.txt cache: ./cache/cord-315730-fzgxuak7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315730-fzgxuak7.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 82277 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-330176-1ugzkf22 author: Weeratunga, Prasanna title: RETRACTED ARTICLE: Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components date: 2016-01-05 pages: extension: .txt txt: ./txt/cord-330176-1ugzkf22.txt cache: ./cache/cord-330176-1ugzkf22.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-330176-1ugzkf22.txt' === file2bib.sh === id: cord-313684-61hkogdh author: Samaddar, Arghadip title: Pathophysiology and Potential Therapeutic Candidates for COVID-19: A Poorly Understood Arena date: 2020-09-17 pages: extension: .txt txt: ./txt/cord-313684-61hkogdh.txt cache: ./cache/cord-313684-61hkogdh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-313684-61hkogdh.txt' === file2bib.sh === id: cord-328804-f7etlk5i author: Olofsson, Peter title: Arthritis suppression by NADPH activation operates through an interferon-β pathway date: 2007-05-09 pages: extension: .txt txt: ./txt/cord-328804-f7etlk5i.txt cache: ./cache/cord-328804-f7etlk5i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328804-f7etlk5i.txt' === file2bib.sh === id: cord-335384-co2fgz26 author: Lobo‐Silva, Diogo title: Interferon‐β regulates the production of IL‐10 by toll‐like receptor‐activated microglia date: 2017-06-15 pages: extension: .txt txt: ./txt/cord-335384-co2fgz26.txt cache: ./cache/cord-335384-co2fgz26.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335384-co2fgz26.txt' === file2bib.sh === id: cord-299754-tgexahwd author: van Tol, Sarah title: The TRIMendous Role of TRIMs in Virus–Host Interactions date: 2017-08-22 pages: extension: .txt txt: ./txt/cord-299754-tgexahwd.txt cache: ./cache/cord-299754-tgexahwd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-299754-tgexahwd.txt' === file2bib.sh === id: cord-338320-jc00ulx5 author: Siu, Kam-Leung title: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain date: 2014-02-10 pages: extension: .txt txt: ./txt/cord-338320-jc00ulx5.txt cache: ./cache/cord-338320-jc00ulx5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338320-jc00ulx5.txt' === file2bib.sh === id: cord-333208-tibtngy8 author: Muñoz-Moreno, Raquel title: Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection date: 2016-04-26 pages: extension: .txt txt: ./txt/cord-333208-tibtngy8.txt cache: ./cache/cord-333208-tibtngy8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333208-tibtngy8.txt' === file2bib.sh === id: cord-337677-ktktqs7b author: Pereda, R. title: Therapeutic effectiveness of interferon alpha 2b treatment for COVID-19 patient recovery date: 2020-08-04 pages: extension: .txt txt: ./txt/cord-337677-ktktqs7b.txt cache: ./cache/cord-337677-ktktqs7b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-337677-ktktqs7b.txt' === file2bib.sh === id: cord-329366-xuszdrsa author: Hackbart, Matthew title: Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors date: 2020-04-07 pages: extension: .txt txt: ./txt/cord-329366-xuszdrsa.txt cache: ./cache/cord-329366-xuszdrsa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329366-xuszdrsa.txt' === file2bib.sh === id: cord-343515-fad1yyqx author: Felgenhauer, Ulrike title: Inhibition of SARS–CoV-2 by type I and type III interferons date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-343515-fad1yyqx.txt cache: ./cache/cord-343515-fad1yyqx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343515-fad1yyqx.txt' === file2bib.sh === id: cord-329190-kv9n2qj3 author: Rabaan, Ali A. title: A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective date: 2017-09-01 pages: extension: .txt txt: ./txt/cord-329190-kv9n2qj3.txt cache: ./cache/cord-329190-kv9n2qj3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329190-kv9n2qj3.txt' === file2bib.sh === id: cord-344798-q34j4zxu author: Villalba, María Caridad Montalvo title: Interferon gamma, TGF-β1 and RANTES expression in upper airway samples from SARS-CoV-2 infected patients date: 2020-08-29 pages: extension: .txt txt: ./txt/cord-344798-q34j4zxu.txt cache: ./cache/cord-344798-q34j4zxu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344798-q34j4zxu.txt' === file2bib.sh === id: cord-340422-8f5xe4zc author: Rowland, R. R. R. title: Inhibition of porcine reproductive and respiratory syndrome virus by interferon-gamma and recovery of virus replication with 2-aminopurine date: 2001 pages: extension: .txt txt: ./txt/cord-340422-8f5xe4zc.txt cache: ./cache/cord-340422-8f5xe4zc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-340422-8f5xe4zc.txt' === file2bib.sh === id: cord-325624-6anybxnk author: Ireland, Derek D. C. title: RNase L Mediated Protection from Virus Induced Demyelination date: 2009-10-02 pages: extension: .txt txt: ./txt/cord-325624-6anybxnk.txt cache: ./cache/cord-325624-6anybxnk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325624-6anybxnk.txt' === file2bib.sh === id: cord-332632-u2ud0vmq author: Lussi, Carmela title: What can pestiviral endonucleases teach us about innate immunotolerance? date: 2016-03-17 pages: extension: .txt txt: ./txt/cord-332632-u2ud0vmq.txt cache: ./cache/cord-332632-u2ud0vmq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332632-u2ud0vmq.txt' === file2bib.sh === id: cord-333463-u7je0d1o author: Diaz-Salazar, Carlos title: Natural killer cell responses to emerging viruses of zoonotic origin date: 2020-08-09 pages: extension: .txt txt: ./txt/cord-333463-u7je0d1o.txt cache: ./cache/cord-333463-u7je0d1o.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-333463-u7je0d1o.txt' === file2bib.sh === id: cord-334134-fhie2m3u author: Mazaleuskaya, Liudmila title: Protective Role of Toll-like Receptor 3-Induced Type I Interferon in Murine Coronavirus Infection of Macrophages date: 2012-05-24 pages: extension: .txt txt: ./txt/cord-334134-fhie2m3u.txt cache: ./cache/cord-334134-fhie2m3u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334134-fhie2m3u.txt' === file2bib.sh === id: cord-335245-1eksm537 author: Pattyn, Els title: HyperISGylation of Old World Monkey ISG15 in Human Cells date: 2008-06-18 pages: extension: .txt txt: ./txt/cord-335245-1eksm537.txt cache: ./cache/cord-335245-1eksm537.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335245-1eksm537.txt' === file2bib.sh === id: cord-345854-f0dq94j1 author: Chong, Wai Po title: The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome date: 2006-05-04 pages: extension: .txt txt: ./txt/cord-345854-f0dq94j1.txt cache: ./cache/cord-345854-f0dq94j1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345854-f0dq94j1.txt' === file2bib.sh === id: cord-328947-3l9ydspz author: Webb, L. G. title: Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-328947-3l9ydspz.txt cache: ./cache/cord-328947-3l9ydspz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328947-3l9ydspz.txt' === file2bib.sh === id: cord-337717-8hcujmuo author: Savarin, Carine title: IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils date: 2012-05-29 pages: extension: .txt txt: ./txt/cord-337717-8hcujmuo.txt cache: ./cache/cord-337717-8hcujmuo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337717-8hcujmuo.txt' === file2bib.sh === id: cord-332154-2gej7h1d author: Meier, William A. title: Cytokines and synthetic double-stranded RNA augment the T helper 1 immune response of swine to porcine reproductive and respiratory syndrome virus date: 2004-12-08 pages: extension: .txt txt: ./txt/cord-332154-2gej7h1d.txt cache: ./cache/cord-332154-2gej7h1d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-332154-2gej7h1d.txt' === file2bib.sh === id: cord-327855-txryqil7 author: Kulka, M. title: The cytopathic 18f strain of Hepatitis A virus induces RNA degradation in FrhK4 cells date: 2003 pages: extension: .txt txt: ./txt/cord-327855-txryqil7.txt cache: ./cache/cord-327855-txryqil7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-327855-txryqil7.txt' === file2bib.sh === id: cord-314505-7qh8dsew author: Stegelmeier, Ashley A. title: Myeloid Cells during Viral Infections and Inflammation date: 2019-02-19 pages: extension: .txt txt: ./txt/cord-314505-7qh8dsew.txt cache: ./cache/cord-314505-7qh8dsew.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-314505-7qh8dsew.txt' === file2bib.sh === id: cord-333423-jhm7u8ka author: Wang, Dang title: Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Type I Interferon Signaling by Targeting IRF9 date: 2019-05-15 pages: extension: .txt txt: ./txt/cord-333423-jhm7u8ka.txt cache: ./cache/cord-333423-jhm7u8ka.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333423-jhm7u8ka.txt' === file2bib.sh === id: cord-343824-00mqmpzw author: Qian, Wei title: The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3 date: 2017-07-03 pages: extension: .txt txt: ./txt/cord-343824-00mqmpzw.txt cache: ./cache/cord-343824-00mqmpzw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343824-00mqmpzw.txt' === file2bib.sh === id: cord-337285-t6qr41wc author: Ikeda, Masanori title: Modulation of host metabolism as a target of new antivirals() date: 2007-10-10 pages: extension: .txt txt: ./txt/cord-337285-t6qr41wc.txt cache: ./cache/cord-337285-t6qr41wc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-337285-t6qr41wc.txt' === file2bib.sh === id: cord-328252-dk54w8z9 author: Kikkert, Marjolein title: Innate Immune Evasion by Human Respiratory RNA Viruses date: 2019-10-14 pages: extension: .txt txt: ./txt/cord-328252-dk54w8z9.txt cache: ./cache/cord-328252-dk54w8z9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328252-dk54w8z9.txt' === file2bib.sh === id: cord-327135-4c2flue4 author: Chinnaswamy, S title: Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections date: 2016-06-09 pages: extension: .txt txt: ./txt/cord-327135-4c2flue4.txt cache: ./cache/cord-327135-4c2flue4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-327135-4c2flue4.txt' === file2bib.sh === id: cord-341278-klv9jdm8 author: Smith, Abigail L. title: The role of gamma interferon in infection of susceptible mice with murine coronavirus, MHV-JHM date: 1991 pages: extension: .txt txt: ./txt/cord-341278-klv9jdm8.txt cache: ./cache/cord-341278-klv9jdm8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341278-klv9jdm8.txt' === file2bib.sh === id: cord-023143-fcno330z author: nan title: Molecular aspects of viral immunity date: 2004-02-19 pages: extension: .txt txt: ./txt/cord-023143-fcno330z.txt cache: ./cache/cord-023143-fcno330z.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023143-fcno330z.txt' === file2bib.sh === id: cord-329618-kywhulpc author: Xu, Cheng title: A de novo transcriptome analysis shows that modulation of the JAK-STAT signaling pathway by salmonid alphavirus subtype 3 favors virus replication in macrophage/dendritic-like TO-cells date: 2016-05-23 pages: extension: .txt txt: ./txt/cord-329618-kywhulpc.txt cache: ./cache/cord-329618-kywhulpc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329618-kywhulpc.txt' === file2bib.sh === id: cord-334624-chnibsa1 author: Hayn, Manuel title: Imperfect innate immune antagonism renders SARS-CoV-2 vulnerable towards IFN-γ and -λ date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-334624-chnibsa1.txt cache: ./cache/cord-334624-chnibsa1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334624-chnibsa1.txt' === file2bib.sh === id: cord-325825-0lyt8gfq author: Griffiths, Samantha J. title: A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date: 2013-08-08 pages: extension: .txt txt: ./txt/cord-325825-0lyt8gfq.txt cache: ./cache/cord-325825-0lyt8gfq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325825-0lyt8gfq.txt' === file2bib.sh === id: cord-353062-c6luoo3m author: Lauber, C title: Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells date: 2015-09-01 pages: extension: .txt txt: ./txt/cord-353062-c6luoo3m.txt cache: ./cache/cord-353062-c6luoo3m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-353062-c6luoo3m.txt' === file2bib.sh === id: cord-354762-3a3a3ku9 author: Afsar, Cigdem Usul title: SARS-CoV-2 (COVID-19): INTERFERON-EPSILON MAY BE RESPONSIBLE OF DECREASED MORTALITY IN FEMALES date: 2020-06-02 pages: extension: .txt txt: ./txt/cord-354762-3a3a3ku9.txt cache: ./cache/cord-354762-3a3a3ku9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-354762-3a3a3ku9.txt' === file2bib.sh === id: cord-307914-lgprrwee author: Bartok, Eva title: Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-307914-lgprrwee.txt cache: ./cache/cord-307914-lgprrwee.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-307914-lgprrwee.txt' === file2bib.sh === id: cord-348684-xbxwpmxq author: Liu, Bao-qin title: Ubiquitination modification: critical regulation of IRF family stability and activity date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-348684-xbxwpmxq.txt cache: ./cache/cord-348684-xbxwpmxq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348684-xbxwpmxq.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-339991-k8z6v2vx author: Rong, Q. title: Multiple mechanisms for HSV-1 induction of interferon α production by peripheral blood mononuclear cells date: 2003 pages: extension: .txt txt: ./txt/cord-339991-k8z6v2vx.txt cache: ./cache/cord-339991-k8z6v2vx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339991-k8z6v2vx.txt' === file2bib.sh === id: cord-353957-0pjg25kn author: Chen, Shilong title: Avian Interferon-Inducible Transmembrane Protein Family Effectively Restricts Avian Tembusu Virus Infection date: 2017-04-20 pages: extension: .txt txt: ./txt/cord-353957-0pjg25kn.txt cache: ./cache/cord-353957-0pjg25kn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-353957-0pjg25kn.txt' === file2bib.sh === id: cord-341478-bicg5ozr author: Aurisicchio, L title: Regulated and prolonged expression of mIFNα in immunocompetent mice mediated by a helper-dependent adenovirus vector date: 2002-01-30 pages: extension: .txt txt: ./txt/cord-341478-bicg5ozr.txt cache: ./cache/cord-341478-bicg5ozr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341478-bicg5ozr.txt' === file2bib.sh === id: cord-017184-1ewi3dka author: nan title: Primary Immunodeficiencies date: 2008 pages: extension: .txt txt: ./txt/cord-017184-1ewi3dka.txt cache: ./cache/cord-017184-1ewi3dka.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-017184-1ewi3dka.txt' === file2bib.sh === id: cord-337365-hugenn14 author: Chen, Zhuangzhuang title: The role of microglia in viral encephalitis: a review date: 2019-04-09 pages: extension: .txt txt: ./txt/cord-337365-hugenn14.txt cache: ./cache/cord-337365-hugenn14.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337365-hugenn14.txt' === file2bib.sh === id: cord-032183-yqqqe325 author: Ning, Qin title: Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure) date: 2019-05-21 pages: extension: .txt txt: ./txt/cord-032183-yqqqe325.txt cache: ./cache/cord-032183-yqqqe325.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-032183-yqqqe325.txt' === file2bib.sh === id: cord-327000-oyg3oyx1 author: Li, Shasha title: Porcine Epidemic Diarrhea Virus and the Host Innate Immune Response date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-327000-oyg3oyx1.txt cache: ./cache/cord-327000-oyg3oyx1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-327000-oyg3oyx1.txt' === file2bib.sh === id: cord-320663-xypg6evo author: Market, Marisa title: Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-320663-xypg6evo.txt cache: ./cache/cord-320663-xypg6evo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-320663-xypg6evo.txt' === file2bib.sh === id: cord-343221-e29of29o author: Kindler, Eveline title: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication date: 2017-02-03 pages: extension: .txt txt: ./txt/cord-343221-e29of29o.txt cache: ./cache/cord-343221-e29of29o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343221-e29of29o.txt' === file2bib.sh === id: cord-275795-ee7qyw5h author: Monette, Anne title: T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders date: 2018-10-24 pages: extension: .txt txt: ./txt/cord-275795-ee7qyw5h.txt cache: ./cache/cord-275795-ee7qyw5h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-275795-ee7qyw5h.txt' === file2bib.sh === id: cord-347225-gh51ag2x author: Fu, Weihui title: A clinical pilot study on the safety and efficacy of aerosol inhalation treatment of IFN-κ plus TFF2 in patients with moderate COVID-19 date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-347225-gh51ag2x.txt cache: ./cache/cord-347225-gh51ag2x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347225-gh51ag2x.txt' === file2bib.sh === id: cord-340475-h0q1m3ed author: Carnero, Elena title: Type I Interferon Regulates the Expression of Long Non-Coding RNAs date: 2014-11-06 pages: extension: .txt txt: ./txt/cord-340475-h0q1m3ed.txt cache: ./cache/cord-340475-h0q1m3ed.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340475-h0q1m3ed.txt' === file2bib.sh === id: cord-348993-8r4fhzlm author: Tomosada, Yohsuke title: Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection date: 2013-08-15 pages: extension: .txt txt: ./txt/cord-348993-8r4fhzlm.txt cache: ./cache/cord-348993-8r4fhzlm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348993-8r4fhzlm.txt' === file2bib.sh === id: cord-354730-hfau2odb author: Wang, Rong title: Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus date: 2014-07-03 pages: extension: .txt txt: ./txt/cord-354730-hfau2odb.txt cache: ./cache/cord-354730-hfau2odb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354730-hfau2odb.txt' === file2bib.sh === id: cord-342189-ya05m58o author: Banerjee, Abhik K. title: SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-342189-ya05m58o.txt cache: ./cache/cord-342189-ya05m58o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-342189-ya05m58o.txt' === file2bib.sh === id: cord-341324-f9g9gitn author: Rojas, José M. title: Viral pathogen-induced mechanisms to antagonize mammalian interferon (IFN) signaling pathway date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-341324-f9g9gitn.txt cache: ./cache/cord-341324-f9g9gitn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341324-f9g9gitn.txt' === file2bib.sh === id: cord-351489-tzmev77c author: Yuan, Shuofeng title: Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-351489-tzmev77c.txt cache: ./cache/cord-351489-tzmev77c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351489-tzmev77c.txt' === file2bib.sh === id: cord-347200-dtwhd6zy author: Ivanova, Daria title: NK Cells in Mucosal Defense against Infection date: 2014-08-14 pages: extension: .txt txt: ./txt/cord-347200-dtwhd6zy.txt cache: ./cache/cord-347200-dtwhd6zy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-347200-dtwhd6zy.txt' === file2bib.sh === id: cord-351845-bli3qm8w author: Prasad, Kartikay title: Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective date: 2020-06-26 pages: extension: .txt txt: ./txt/cord-351845-bli3qm8w.txt cache: ./cache/cord-351845-bli3qm8w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351845-bli3qm8w.txt' === file2bib.sh === id: cord-353337-o302vxqm author: Visser, Linda J. title: Dissecting distinct proteolytic activities of FMDV L(pro) implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-353337-o302vxqm.txt cache: ./cache/cord-353337-o302vxqm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353337-o302vxqm.txt' === file2bib.sh === id: cord-347460-9vechh4x author: Chang, Feng-Yee title: Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) date: 2020-06-04 pages: extension: .txt txt: ./txt/cord-347460-9vechh4x.txt cache: ./cache/cord-347460-9vechh4x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-347460-9vechh4x.txt' === file2bib.sh === id: cord-351532-2yd4wg9v author: Huang, Yin-Qiu title: No Statistically Apparent Difference in Antiviral Effectiveness Observed Among Ribavirin Plus Interferon-Alpha, Lopinavir/Ritonavir Plus Interferon-Alpha, and Ribavirin Plus Lopinavir/Ritonavir Plus Interferon-Alpha in Patients With Mild to Moderate Coronavirus Disease 2019: Results of a Randomized, Open-Labeled Prospective Study date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-351532-2yd4wg9v.txt cache: ./cache/cord-351532-2yd4wg9v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351532-2yd4wg9v.txt' === file2bib.sh === id: cord-006444-eq56zhtd author: nan title: Abstracts of oral presentations and posters date: 1993 pages: extension: .txt txt: ./txt/cord-006444-eq56zhtd.txt cache: ./cache/cord-006444-eq56zhtd.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006444-eq56zhtd.txt' === file2bib.sh === id: cord-355671-t890eixt author: Medina, Gisselle N. title: Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-355671-t890eixt.txt cache: ./cache/cord-355671-t890eixt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-355671-t890eixt.txt' === file2bib.sh === id: cord-356197-js7l86fh author: Zhou, Ping title: Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo date: 2011-08-07 pages: extension: .txt txt: ./txt/cord-356197-js7l86fh.txt cache: ./cache/cord-356197-js7l86fh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-356197-js7l86fh.txt' === file2bib.sh === id: cord-354000-jxqskt4k author: Warren, Cody J. title: The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date: 2014-05-14 pages: extension: .txt txt: ./txt/cord-354000-jxqskt4k.txt cache: ./cache/cord-354000-jxqskt4k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-354000-jxqskt4k.txt' === file2bib.sh === id: cord-346836-6jyv0q5e author: Ikegami, Tetsuro title: The Pathogenesis of Rift Valley Fever date: 2011-05-06 pages: extension: .txt txt: ./txt/cord-346836-6jyv0q5e.txt cache: ./cache/cord-346836-6jyv0q5e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-346836-6jyv0q5e.txt' === file2bib.sh === id: cord-356094-sbtigcfr author: Chen, Huijie title: Antiviral Activity Against Infectious Bronchitis Virus and Bioactive Components of Hypericum perforatum L. date: 2019-10-29 pages: extension: .txt txt: ./txt/cord-356094-sbtigcfr.txt cache: ./cache/cord-356094-sbtigcfr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-356094-sbtigcfr.txt' === file2bib.sh === id: cord-353826-owoec2ud author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-353826-owoec2ud.txt cache: ./cache/cord-353826-owoec2ud.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-353826-owoec2ud.txt' === file2bib.sh === id: cord-344093-3bniy5b5 author: Peteranderl, Christin title: The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond date: 2017-03-22 pages: extension: .txt txt: ./txt/cord-344093-3bniy5b5.txt cache: ./cache/cord-344093-3bniy5b5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-344093-3bniy5b5.txt' === file2bib.sh === id: cord-355839-o0m71kvw author: Sedeyn, Koen title: Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses date: 2019-10-17 pages: extension: .txt txt: ./txt/cord-355839-o0m71kvw.txt cache: ./cache/cord-355839-o0m71kvw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-355839-o0m71kvw.txt' === file2bib.sh === id: cord-354620-xf6glr2h author: Tian, Bin title: Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus date: 2020-01-28 pages: extension: .txt txt: ./txt/cord-354620-xf6glr2h.txt cache: ./cache/cord-354620-xf6glr2h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-354620-xf6glr2h.txt' === file2bib.sh === id: cord-351520-c5fi2uoh author: Zhong, Bo title: Regulation of virus-triggered type I interferon signaling by cellular and viral proteins date: 2010-02-01 pages: extension: .txt txt: ./txt/cord-351520-c5fi2uoh.txt cache: ./cache/cord-351520-c5fi2uoh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-351520-c5fi2uoh.txt' === file2bib.sh === id: cord-342800-62jklwiy author: Xu, Shuqin title: mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-342800-62jklwiy.txt cache: ./cache/cord-342800-62jklwiy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342800-62jklwiy.txt' === file2bib.sh === id: cord-349647-cfjrwt44 author: Girkin, Jason title: Chapter 8 In vivo experimental models of infection and disease date: 2019-12-31 pages: extension: .txt txt: ./txt/cord-349647-cfjrwt44.txt cache: ./cache/cord-349647-cfjrwt44.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349647-cfjrwt44.txt' === file2bib.sh === id: cord-343963-99rd3o79 author: Wong, Mun-Teng title: Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection date: 2014-12-29 pages: extension: .txt txt: ./txt/cord-343963-99rd3o79.txt cache: ./cache/cord-343963-99rd3o79.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-343963-99rd3o79.txt' === file2bib.sh === id: cord-347946-i6kx3n6m author: Raison, Charles L title: Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance date: 2016-09-15 pages: extension: .txt txt: ./txt/cord-347946-i6kx3n6m.txt cache: ./cache/cord-347946-i6kx3n6m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-347946-i6kx3n6m.txt' === file2bib.sh === id: cord-347298-7kqrl3rv author: Hedger, M.P. title: Immunology of the Testis and Male Reproductive Tract date: 2010-07-12 pages: extension: .txt txt: ./txt/cord-347298-7kqrl3rv.txt cache: ./cache/cord-347298-7kqrl3rv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-347298-7kqrl3rv.txt' === file2bib.sh === id: cord-337458-dc90ecfe author: Markwalter, Christine F. title: Inorganic Complexes and Metal-Based Nanomaterials for Infectious Disease Diagnostics date: 2018-12-04 pages: extension: .txt txt: ./txt/cord-337458-dc90ecfe.txt cache: ./cache/cord-337458-dc90ecfe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-337458-dc90ecfe.txt' === file2bib.sh === id: cord-015147-h0o0yqv8 author: nan title: Oral Communications and Posters date: 2014-09-12 pages: extension: .txt txt: ./txt/cord-015147-h0o0yqv8.txt cache: ./cache/cord-015147-h0o0yqv8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-015147-h0o0yqv8.txt' === file2bib.sh === id: cord-004675-n8mlxe7p author: nan title: 2019 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date: 2019-02-26 pages: extension: .txt txt: ./txt/cord-004675-n8mlxe7p.txt cache: ./cache/cord-004675-n8mlxe7p.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-004675-n8mlxe7p.txt' === file2bib.sh === id: cord-024651-578c9ut5 author: nan title: 2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-024651-578c9ut5.txt cache: ./cache/cord-024651-578c9ut5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-024651-578c9ut5.txt' === file2bib.sh === id: cord-007890-bie1veti author: nan title: ECC-4 Abstracts date: 2002-04-16 pages: extension: .txt txt: ./txt/cord-007890-bie1veti.txt cache: ./cache/cord-007890-bie1veti.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 10 resourceName b'cord-007890-bie1veti.txt' === file2bib.sh === id: cord-000083-3p81yr4n author: nan title: Poster Exhibition date: 2009-01-31 pages: extension: .txt txt: ./txt/cord-000083-3p81yr4n.txt cache: ./cache/cord-000083-3p81yr4n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 20 resourceName b'cord-000083-3p81yr4n.txt' === file2bib.sh === id: cord-009567-osstpum6 author: nan title: Abstracts Oral date: 2008-04-23 pages: extension: .txt txt: ./txt/cord-009567-osstpum6.txt cache: ./cache/cord-009567-osstpum6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 13 resourceName b'cord-009567-osstpum6.txt' === file2bib.sh === id: cord-015021-pol2qm74 author: nan title: Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date: 1994 pages: extension: .txt txt: ./txt/cord-015021-pol2qm74.txt cache: ./cache/cord-015021-pol2qm74.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 23 resourceName b'cord-015021-pol2qm74.txt' === file2bib.sh === id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 pages: extension: .txt txt: ./txt/cord-022888-dnsdg04n.txt cache: ./cache/cord-022888-dnsdg04n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 16 resourceName b'cord-022888-dnsdg04n.txt' Que is empty; done keyword-ifn-cord === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-000478-88wo4xen author = Gowen, Brian B. title = Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection date = 2011-10-24 pages = extension = .txt mime = text/plain words = 4407 sentences = 221 flesch = 49 summary = Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. Interestingly, the 10 7 and 10 8 pfu DEF201 groups presented with little to no day-7 virus burden in the serum, liver, or spleen, while the 10 6 group developed viral titers that were comparable to the rAd EV and placebo controls ( Figure 2B-D) . This may not be the case with hamsters treated with DEF201 24 h prior to challenge since most had no detectable virus titers in spleen, liver, or serum on day 7 of PICV infection ( Figure 2B-D) . Animals were treated i.n. with a single dose 10 8 pfu of DEF201, the rAd EV control virus, or PBS placebo 7 or 14 days prior to PICV infection. cache = ./cache/cord-000478-88wo4xen.txt txt = ./txt/cord-000478-88wo4xen.txt === reduce.pl bib === id = cord-000125-uvf5qzfd author = Kenworthy, Rachael title = Short-hairpin RNAs delivered by lentiviral vector transduction trigger RIG-I-mediated IFN activation date = 2009-09-03 pages = extension = .txt mime = text/plain words = 6633 sentences = 336 flesch = 54 summary = The interaction between a PAMP and a PRR triggers activation of the interferon (IFN) pathway in mammalian cells, which significantly changes the gene-expression profile in the cells and contributes to the well-documented off-target effect of RNAi. IFN induction is especially problematic in antiviral studies employing RNAi, where the antiviral effect of IFN must be distinguished from that of RNAi. Typical IFN-inducing structure patterns include dsRNA of certain length, single-stranded RNA (ssRNA) containing 5 0 -triphosphates (5 0 -ppp), the dsRNA analogue polyinosinic-polycytidylic acid (poly I:C), and certain dsDNA molecules. Mammalian expression plasmids encoding each of these proteins, as well as the dominant negative (DN) mutants of RIG-I and MDA5, were transfected into 293FT cells with shRNAs and an IFN-b promoter reporter construct. cache = ./cache/cord-000125-uvf5qzfd.txt txt = ./txt/cord-000125-uvf5qzfd.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-000554-p4ufea6x author = Gao, Wei title = Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus date = 2012-01-18 pages = extension = .txt mime = text/plain words = 5516 sentences = 289 flesch = 54 summary = title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus We have also observed cross-talk between MAP kinase and NFkB pathways, and our data indicate that MAP kinase ERK1/2 and JNK1/2 may impact the activation of NFkB through the induction of RIG-1, leading to IFN-b induction in H1N1pdm-infected swine macrophages. To understand the mechanism of proinflammatory cytokine and TNF family ligand induction in H1N1pdm-infected swine macrophages, we investigated how MAP kinases were activated and whether their signaling pathways were involved in the regulation of various cytokines and TNF family ligands in pig immune cells. To evaluate the role of MAP kinases in the regulation of proinflammatory cytokine responses in H1N1pdm-infected swine macrophages, we pre-treated 3D/4 cells with specific inhibitors for ERK1/2, p38, and JNK1/2 1 hr prior to infection. cache = ./cache/cord-000554-p4ufea6x.txt txt = ./txt/cord-000554-p4ufea6x.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-000409-lpf9lpky author = Chen, Yongwen title = Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection date = 2011-07-07 pages = extension = .txt mime = text/plain words = 5540 sentences = 296 flesch = 49 summary = Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. In all, these results demonstrated that PD-1 deficiency led to enhanced pathological damage by MHV-3 in the liver, spleen, lymph node and thymus, where higher levels of PD-1-positive cells were found after infection. Results showed that the expression of FGL2 was principally associated with CD31-positive endothelial cells, CD68-positive macrophages and CD11c-positive DCs. Surprisingly, significantly higher levels of FGL2 were observed after infection in all of PD-1-deficient organs, including the liver, thymus, spleen, lymph nodes, and serum than that in those from WT littermates. However, the number of Foxp3-positive cells in the liver, spleen, lymph node or thymus was not significantly different between PD-1-deficient mice and their WT littermates after 72 h of MHV-3 infection (Fig. S3) . cache = ./cache/cord-000409-lpf9lpky.txt txt = ./txt/cord-000409-lpf9lpky.txt === reduce.pl bib === id = cord-000725-rafwlw0t author = Hindinger, Claudia title = IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date = 2012-07-27 pages = extension = .txt mime = text/plain words = 5114 sentences = 243 flesch = 37 summary = Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. GFAPcR1D and wt mice were compared at the peak of acute disease to determine if IFN-c signaling altered astrocyte activation or CNS inflammation. Despite elevated demyelination and axonal loss in the absence of IFN-c signaling to astrocytes, spinal cords showed no evidence of differential astrocyte activation by either immunohistochemistry (Fig. 4 ), or differences in GFAP mRNA expression during the peak of acute disease (Fig. 5 ). Although demyelination was increased in the CNS of GFAPcR1D mice, the extent of astrocyte activation associated with spinal cord white matter lesions was similar in both groups ( Fig. 6 ; ,60 GFAP + cells/mm 2 ). cache = ./cache/cord-000725-rafwlw0t.txt txt = ./txt/cord-000725-rafwlw0t.txt === reduce.pl bib === === reduce.pl bib === id = cord-001808-47496o0e author = Bayat, Ahmad title = Anti-cytokine autoantibodies in postherpetic neuralgia date = 2015-10-20 pages = extension = .txt mime = text/plain words = 4246 sentences = 213 flesch = 50 summary = Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN. High levels of neutralizing anti-IFN-γ autoantibodies were also detected in patients with disseminated nontuberculous mycobacteria and other opportunistic infections, including both with localized and disseminated VZV reactivation [14, 15] . The finding that several patients each harbored single, neutralizing autoantibodies against interferon-α, GM-CSF or IL-6 suggests that anti-cytokine immunodeficiency may contribute to development of PHN. Particularly relevant was the finding of six PHN patients (one against anti-IFN-α, three against IFN-γ, one against GM-CSF, and one against IL-6) with high levels of autoantibodies greater than 100,000 LU that might have potential neutralizing activity against the target (Fig. 1) . cache = ./cache/cord-001808-47496o0e.txt txt = ./txt/cord-001808-47496o0e.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-002630-5616n73p author = Dargahi, Narges title = Multiple Sclerosis: Immunopathology and Treatment Update date = 2017-07-07 pages = extension = .txt mime = text/plain words = 11316 sentences = 561 flesch = 47 summary = We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS. Based on Phase III human clinical trials in patients with RRMS (TRANSFORMS, FREEDOMS and FREEDOMS II), fingolimod was more effective compared to first line treatment IFNβ-1a and placebo, in reducing the frequency of flare-ups (clinical exacerbations), disability progression, MRI outcome measures, including brain volume loss and was associated with clearly identified adverse events [103, 136, 137] . Citrullination of linear and cyclic altered peptide ligands from myelin basic protein (mbp(87-99)) epitope elicits a th1 polarized response by t cells isolated from multiple sclerosis patients: Implications in triggering disease cache = ./cache/cord-002630-5616n73p.txt txt = ./txt/cord-002630-5616n73p.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-000660-tsvzg0ax author = Fensterl, Volker title = Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis date = 2012-05-17 pages = extension = .txt mime = text/plain words = 8283 sentences = 446 flesch = 55 summary = Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. In contrast, in acute infection by viruses that cause severe pathogenesis and death within a few days after infection, protection is primarily provided by the intrinsic antiviral actions of IFN-induced proteins encoded by the hundreds of IFN-stimulated genes (ISGs) [10] [11] [12] , several of which often contribute to the overall effect of IFN against a given virus. From the above observations, we conclude that after intranasal infection by VSV, Ifit2 protects mice from neuropathogenesis by suppressing replication or spread of the virus in brain neurons. In the complete absence of type I IFN action in the IFNAR 2/2 mice, intranasally infected VSV replicated vigorously not only in brains, but also in livers and lungs ( Figure 7A-C) . cache = ./cache/cord-000660-tsvzg0ax.txt txt = ./txt/cord-000660-tsvzg0ax.txt === reduce.pl bib === === reduce.pl bib === id = cord-001515-x11t9pbv author = Kosinska, Anna D. title = Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck date = 2014-12-23 pages = extension = .txt mime = text/plain words = 6390 sentences = 312 flesch = 37 summary = Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. The results of these studies clearly showed that combination of antiviral treatment and vaccination is more effective in inducing virus-specific T cell responses than therapeutic vaccination alone. The DNA prime-AdV boost immunization strategy was further used as a therapeutic vaccine against chronic WHV infection in combination with antiviral treatment with ETV. T-helper cell response to woodchuck hepatitis virus antigens after therapeutic vaccination of chronically-infected animals treated with lamivudine cache = ./cache/cord-001515-x11t9pbv.txt txt = ./txt/cord-001515-x11t9pbv.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-001546-ndz3oarf author = Ayithan, Natarajan title = Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date = 2015-02-26 pages = extension = .txt mime = text/plain words = 5128 sentences = 298 flesch = 52 summary = Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. The aim of this study was to further investigate molecular bases of postexposure protection by VLPs. Based on our previous report that VLPs stimulate type I IFN expression in DCs and macrophages, in vitro, we focused on the role of type I IFN signaling, and found that post-exposure VLP treatment leads to accelerated activation of IFN signaling, resulting in early induction of ISGs. Significantly, VLP stimulated ISG induction coincided with the attenuation of proinflammatory cytokine surge in EBOV infected mice. cache = ./cache/cord-001546-ndz3oarf.txt txt = ./txt/cord-001546-ndz3oarf.txt === reduce.pl bib === id = cord-001848-idmj2d7p author = Onabajo, Olusegun O. title = Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells date = 2015-11-01 pages = extension = .txt mime = text/plain words = 7203 sentences = 335 flesch = 47 summary = We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Previously, we showed that transient transfection of an expression construct that generates IFN-l4 protein induced interferon signaling, with activation of interferon-stimulated genes (ISGs) and generation of antiviral response in HepG2, a human hepatoma cell line (Prokunina-Olsson and others 2013). The stable HepG2-ISRE-Luc cells were transfected with corresponding constructs in 96-well plates; untransfected cells were treated with human recombinant interferons-IFNa (2 ng/mL; PBL Assay Science) or custom IFN-l3 (10 ng/ mL). Previously, by performing Western blot analysis, we were unable to detect IFN-l4 in culture media of HepG2 cells transiently transfected with an IFN-l4-producing construct, even though this transfection resulted in strong activation of interferon signaling (Prokunina-Olsson and others 2013). IFN-l4 was detectable in culture media of IFNL4-transfected PHHs and HepG2 cells, but not in corresponding Halo-transfected cells (Fig. 2B) . cache = ./cache/cord-001848-idmj2d7p.txt txt = ./txt/cord-001848-idmj2d7p.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-004341-co9s26x1 author = Thukral, Akanksha title = A single dose polyanhydride-based nanovaccine against paratuberculosis infection date = 2020-02-14 pages = extension = .txt mime = text/plain words = 6736 sentences = 375 flesch = 43 summary = Pre-challenge immune responses For Trial I (i.e., safety study), the T cell response was evaluated at 6 weeks post-vaccination by performing IFN-γ ELISA on spleen derived lymphocytes (described in Methods) (Supplemental Fig. 1 ). Post-challenge immune responses To evaluate T cell response in Trial I/safety study IFN-γ ELISA was performed and result of which depicted no significant differences in IFN-γ levels among the groups (Supplemental Fig. 2b ) while at 12 weeks post challenge Mycopar and PAN-lysate vaccinated animals showed significantly higher IFN-γ levels as compared with control animals given PBS (Supplemental Fig. 2c ). At 12 WPC, multiparametric flow cytometry analysis indicated that mice immunized with PAN-Cf elicited a significantly higher percent of antigen specific double cytokine (IFN-γ, TNF-α + ) and single cytokine (IFN-γ) producing CD8 + T cells compared with non-vaccinated and Mycopar® vaccinated mice (Fig. 4 ). cache = ./cache/cord-004341-co9s26x1.txt txt = ./txt/cord-004341-co9s26x1.txt === reduce.pl bib === === reduce.pl bib === id = cord-001397-nrq4ncdf author = Mlera, Luwanika title = The role of viral persistence in flavivirus biology date = 2014-05-12 pages = extension = .txt mime = text/plain words = 15593 sentences = 812 flesch = 46 summary = Avenues for additional studies include determining if the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence as well as investigating the host responses that allow vector borne flavivirus replication without detrimental effects on infected cells. The SL1 structure is essential for viral replication and acts as a promoter which is targeted initially by NS5 and then delivered to the 3 0 end via cyclization (Filomatori et al., 2006; Zhang et al., 2008; Lodeiro et al., 2009) Although there is low nucleotide conservation between flaviviruses and different CS homology (Hahn et al., 1987) , the 5 0 UTRs of TBFVs share the same genomic organization as the MBFVs (Kofler et al., 2006) Structural proteins Capsid (C) 11 kDa, 114 aa Cytosol/nucleus The capsid protein is a dimeric alpha-helical (Jones et al., 2003) protein and assembles into an icosahedral structure, measuring 30 nm in diameter, which initiates encapsidation of the associated genomic RNA in virus-induced membrane invaginations of the ER (Welsch et al., 2009 ). cache = ./cache/cord-001397-nrq4ncdf.txt txt = ./txt/cord-001397-nrq4ncdf.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-003855-so8xl199 author = Ebert, Gregor title = Virology Downunder, a meeting commentary from the 2019 Lorne Infection and Immunity Conference, Australia date = 2019-09-02 pages = extension = .txt mime = text/plain words = 1899 sentences = 95 flesch = 39 summary = The bat innate immune response appears to be 'pre-activated' with higher basal levels of type I interferon expression, in contrast to humans, who are very quick responders to viral infections, but require a lot more dampening of their immune signals afterwards to get back to basal levels. demonstrated that bats' response to stress in form of viral infections is more targeted and thus potentially more effective by numerous adaptions and modifications of the innate immune system. In the 'Pathogenesis and Prevention of Infection' session, Rosa Coldbeck-Shackley working with Michael Beard at the University of Adelaide, Australia, and also colleagues at the Hudson Institute, presented findings on the importance of interferon-epsilon (IFN-ɛ) in the innate immune response to ZIKV infection. Also in the 'Pathogenesis and Prevention of Infection' session, Allison Abendroth (University of Sydney) presented 'Disarming the killer: targeting of natural killer cells by varicella zoster virus'. cache = ./cache/cord-003855-so8xl199.txt txt = ./txt/cord-003855-so8xl199.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-005953-5z89yeb6 author = nan title = Abstracts des 114. Internistenkongresses 2008 date = 2008 pages = extension = .txt mime = text/plain words = 16135 sentences = 1522 flesch = 49 summary = Die anderen beiden Gruppen zeigten zwar in Hinblick auf die Wandstärken einen positiven Effekt, hinsichtlich der Herzfunktion konnten sie jedoch bei bereits deutlich erniedrigten Funktionswerten zum Baseline-Zeitpunkt lediglich stabilisiert werden (Reduktion der Wandstärke nach 3 Jahren ERT: Gruppe wenig Fibrose= 10 mm; Gruppe viel Fibrose= 12 mm) Schlussfolgerung: Die Enzymersatztherapie ist eine effektive Langzeitbehandlung bei Patienten mit Fabry Kardiomyopathie. Der Einfluss der sauren Sphingomyelinase auf die Expression von Matrix-Metalloproteinase-1 in intestinalen Epithelzellen und Fibroblasten Background: The calcineurin (Cn)/NF-AT signaling cascade takes a crucial role during T-cell activation and the development of myocardial hypertrophy. Effective and safe reduction of blood pressue by the combination of amlodipine 5/valsartan 160 mg in patients with hypertension and metabolic risk factors not controlled by amlodipine 5 mg or felodipine 5 mga subanalysis of the express-m trial Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia and frequently occurs in patients with coronary heart disease. cache = ./cache/cord-005953-5z89yeb6.txt txt = ./txt/cord-005953-5z89yeb6.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-007696-83v9yfa6 author = Zisman, David A. title = Pulmonary Fibrosis date = 2005 pages = extension = .txt mime = text/plain words = 13991 sentences = 691 flesch = 40 summary = Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease limited to the lungs and associated with the histologic appearance of usual interstitial pneumonia (UIP) on surgical lung biopsy. Factors that predict poor outcome include older age, male gender, severe dyspnea, history of cigarette smoking, severe loss of lung function, appearance and severity of fibrosis on radiological studies, lack of response to therapy, and prominent fibroblastic foci on histopathologic evaluation. With greater comprehension of the clinical relevance of the different histopathological subgroups that make up the idiopathic interstitial pneumonias, the term idiopathic pulmonary fibrosis (IPF) is now reserved to patients with idiopathic usual interstitial pneumonia (UIP) on surgical lung biopsy. Tang In a recent study, human T-lymphtropic virus type I (HTVL-I) positive IPF patients had more affected lung parenchyma, demonstrated traction bronchiectasis with honeycomb change, and exhibited increased levels of specific cytokines that correlated with activated T-cells in the bronchoalveolar lavage fluid (BALF). cache = ./cache/cord-007696-83v9yfa6.txt txt = ./txt/cord-007696-83v9yfa6.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-012497-n5pu1yeu author = Rogers, Meredith C. title = STAT2 Limits Host Species Specificity of Human Metapneumovirus date = 2020-07-04 pages = extension = .txt mime = text/plain words = 6400 sentences = 333 flesch = 53 summary = Finally, we sought to understand the in vivo role of STAT2 by infecting hSTAT2 knock-in mice with HMPV, and found that mice had increased weight loss, inhibition of type I interferon signaling, and a Th2-polarized cytokine profile compared to WT mice. Mouse models for HMPV have been developed, but mice are only semi-permissive for HMPV, requiring a high viral inoculum for productive in vivo infection ( [25] and unpublished observations), which may be due to species differences in the innate immune proteins antagonized by the virus. To better understand the global consequences of substituting human STAT2 into mice in vivo, we performed multiplex cytokine analysis on lung homogenates of HMPV-infected hSTAT2 KI and WT mice at day five after high-dose inoculation, as day five represents a time point that bridges innate and adaptive immunity. cache = ./cache/cord-012497-n5pu1yeu.txt txt = ./txt/cord-012497-n5pu1yeu.txt === reduce.pl bib === id = cord-006444-eq56zhtd author = nan title = Abstracts of oral presentations and posters date = 1993 pages = extension = .txt mime = text/plain words = 40668 sentences = 2121 flesch = 53 summary = The results from ongoing preclinical studies continue to confirm the broad spectrum of biological activities possessed by rhiL-1 1 in vitro and suggest this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation. We performed a phase H trial to assess the ability of G-CSF -mobilized PBPC to rapidly and completely restore hemopeiesis after high dose chemotherapy in the absence of bone marrow infusions, with selection for PBPC-only infusions based on yield of granulocyte -macrophage colony -forming cells (GM-CFC) after G-CSF treatment. Our approach for high-dose (HD) chemotherapy is to first treat patients eligible for dose intensification with a standard dose chemotherapy (VIP: VP26 = etoposide: 500 mg/m 2, ifosfamide: 4 g/m 2, cis-platinum: 50 mg/m 2) followed by the application of colony stimulating factors (G-CSF, GM-CSF or IL-3 + GM-CSF) in order to combine a regimen with broad anti-tumor activity with the recruitment of peripheral blood progenitor cells (PBPCs). cache = ./cache/cord-006444-eq56zhtd.txt txt = ./txt/cord-006444-eq56zhtd.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-005664-n4xv247l author = Plötz, Frans B. title = Mechanical ventilation alters the immune response in children without lung pathology date = 2002-01-15 pages = extension = .txt mime = text/plain words = 3292 sentences = 182 flesch = 41 summary = In the tracheal aspirates the immune balance was characterized by a proinflammatory response pattern, with a significant increase in TNF-α and IL-6 concentrations; concentrations of anti-inflammatory mediators remained very low. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. The major finding of the present study is that exposing infants with normal lung function to 2 h of volatile anesthetics, mechanical ventilation, and cardiac catheterization is associated with remarkable changes in immune responses. We observed a proinflammatory response in the lungs with a significant increase in TNF-α, while antiinflammatory cytokine concentrations in tracheal aspirates remained virtually unchanged, just above the detection level. cache = ./cache/cord-005664-n4xv247l.txt txt = ./txt/cord-005664-n4xv247l.txt === reduce.pl bib === === reduce.pl bib === id = cord-007013-tlvgyzft author = Chan, Kok Fei title = Investigating Viral Interference Between Influenza A Virus and Human Respiratory Syncytial Virus in a Ferret Model of Infection date = 2018-08-01 pages = extension = .txt mime = text/plain words = 4939 sentences = 320 flesch = 49 summary = Previously, we used the ferret model to demonstrate that viral interference can occur following infection with human influenza A and B viruses and will prevent, delay, or limit subsequent infection with an influenza virus of a different type, subtype, or lineage [10, 11] . The peak of hRSV shedding was delayed in ferrets infected with A(H1N1)pdm09 followed by hRSV as compared to control animals infected with hRSV alone (median, 8 vs 6 days; P = .0091 by the Mann-Whitney test; Figure 2Ci ). The median duration of A(H1N1)pdm09 shedding was increased in ferrets infected with hRSV followed by A(H1N1)pdm09 as compared to control animals infected with A(H1N1)pdm09 alone (8 vs 7 days; P = .0196 by the Mann-Whitney test; Figure 2Civ ). Notably, increased expression of inflammatory mediators following infection with influenza virus as compared to hRSV has been observed in studies assessing human clinical samples and in vitro airway epithelial cell cultures [36] [37] [38] [39] . cache = ./cache/cord-007013-tlvgyzft.txt txt = ./txt/cord-007013-tlvgyzft.txt === reduce.pl bib === id = cord-007664-c5snhymz author = Mauerhoff, Thekla title = Differential expression and regulation of major histocompatibility complex (MHC) products in neural and glial cells of the human fetal brain date = 2002-11-13 pages = extension = .txt mime = text/plain words = 4673 sentences = 212 flesch = 51 summary = To gain an insight into the regulation of HLA in the different cell types in the CNS and to compare it to that observed in the endocrine organs, we have studied the effect of the lympho/monokines interferon (IFN)-α and -γ, tumour necrosis factor (TNF)-α, and interleukin (IL)-2 and other agents on this aspect of the biology of human fetal brain cells in culture. It has previously been reported that primary cultures of human fetal brain tissue can be a useful substrate for studying the expression of cell type-specific antigens, e.g. gangliosides, tetanus toxin receptors (Dickson et al., 1982 (Dickson et al., , 1985 , and the present data confirm that they can also be successfully employed to investigate the expression and modulation of HLA molecules. cache = ./cache/cord-007664-c5snhymz.txt txt = ./txt/cord-007664-c5snhymz.txt === reduce.pl bib === id = cord-003514-yyzbv7ys author = Arslan, Mehboob title = Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken date = 2019-02-14 pages = extension = .txt mime = text/plain words = 6080 sentences = 326 flesch = 44 summary = The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Although CEF do not possess receptors for IFN-λ, slight temporal expression of DEGs in response to chIFN-λ treatment signifies its antiviral potential in primary cells. Furthermore, studies have also revealed that a high degree of cell type specificity in receptor-ligand interactions make avian IFNs distinct from mammalian IFNs. Recently, it has been established that chicken IFN-λ inhibits low pathogenic influenza virus replication in CEFs; however, as compared to chIFN-γ and chIFN-β, higher doses are required to induce ISGs and maintain the strong antiviral state in the cells [14] . Our data suggest that significant antiviral, cell cycle regulators, and biologically active genes are expressed in response to administered chicken IFN. cache = ./cache/cord-003514-yyzbv7ys.txt txt = ./txt/cord-003514-yyzbv7ys.txt === reduce.pl bib === id = cord-004685-qote5nx2 author = Vassão, R. C. title = A genetic analysis of macrophage activation and specific antibodies in relation to the resistance of heterogeneous mouse populations to MHV3 infection date = 1994 pages = extension = .txt mime = text/plain words = 2352 sentences = 113 flesch = 42 summary = The data indicate, among the mechanisms of resistance against the virus infection, a role of IFN gamma macrophage-activation and of antibodies against MHV3 which may delay the mean survival time in susceptible animals. The virus replication in target cells, the antiviral state induced by interferon (IFN) and the expression of a monokine with procoagulant activity (PCA) have been implicated in the resistance/susceptibility of the genetic homogeneous or heterogeneous mouse populations to the MHV3 infection [t, 2, 4, 7, 17, 18, 23, 243 . For the study of the individual correlation between in vivo resistance and in vitro inhibition of virus replication by IFN gamma, peritoneal macrophages from Hm, Lm and F 2 segregants were collected without sacrificing the animals, which were infected with MHV3 a week later. This brings further support to our previous suggestion that one of the main mechanisms involved in the resistance of mice to the MHV3 infection is based on the ability of their macrophages to restrict the virus replication upon IFN gamma activation [10 13, 153 . cache = ./cache/cord-004685-qote5nx2.txt txt = ./txt/cord-004685-qote5nx2.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-008821-rxzgfk1k author = A. Lucchiari, Maria title = In vivo depletion of interferon-gamma leads to susceptibility of A/J mice to mouse hepatitis virus 3 infection date = 2011-11-02 pages = extension = .txt mime = text/plain words = 2416 sentences = 97 flesch = 45 summary = Abbreviations; MHV3 = mouse hepatitis virus 3; IFN = interferon; Fes = fetal calf serum; PFU = plaque-forming units; ip = intraperitoneally; Ab = antibodies; PBS = phosphate buffer solution against our strain of MHV3 is acquired after immunization and the mechanism involved is dependent on the IFN -y synthesis and the macrophage sensitivity to IFN-y (9). Although, in view of the crucial regulatory function of CD4 cells and the important role of CDS cells as cytotoxic effector cells during a virusspecific immune response, the results cannot unequivocally exclude the interpretation that susceptibility of the immunosuppressed animals may be due to the absence of proper immune effector mechanisms, the lack of clearance of the virus in the peritoneum and liver of AI] treated and infected mice (Figure 1) , which leads to high rates of mortality (Table 1) , may be attributed to the lack of IFN-y in the serum or peritoneal exudate of them (Fig. 3) , which has been shown in vitro to be effective to restrict the MHV3 growth in target cells such as macrophages (6, 7, 9) . cache = ./cache/cord-008821-rxzgfk1k.txt txt = ./txt/cord-008821-rxzgfk1k.txt === reduce.pl bib === id = cord-007646-yh8zi1ee author = Weiss, R.C. title = Effect of recombinant human interferon-alpha in vitro and in vivo on mitogen-induced lymphocyte blastogenesis in cats() date = 2002-11-12 pages = extension = .txt mime = text/plain words = 3828 sentences = 199 flesch = 48 summary = The effect of recombinant human interferon-alpha (rHuIFN-α) in vitro and in vivo on mitogen-induced lymphocyte blastogenesis was evaluated in specific-pathogen-free cats. Pre-incubation of isolated feline peripheral blood lymphocytes (PBL) in vitro with either 104 or 103 International Units (U) of rHuIFN-o~ for 24 h significantly suppressed (P < 0.001 and 0.01, respectively) blastogenic responses to the phytomitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Pre-incubation of isolated feline peripheral blood lymphocytes (PBL) in vitro with either 104 or 103 International Units (U) of rHuIFN-o~ for 24 h significantly suppressed (P < 0.001 and 0.01, respectively) blastogenic responses to the phytomitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Although the suppressive mechanism (s) associated with rHuIFN-c~ on DNA synthesis and lymphocyte blastogenesis were not investigated in our study, it is possible that high doses of IFN in vitro enhanced lectin-binding on lymphocytes and stimulated suppressor cell activities. cache = ./cache/cord-007646-yh8zi1ee.txt txt = ./txt/cord-007646-yh8zi1ee.txt === reduce.pl bib === id = cord-007796-zggk0x2q author = Lindemans, Caroline A. title = The Immune Response to Viral Lower Respiratory Tract Infection date = 2005 pages = extension = .txt mime = text/plain words = 9767 sentences = 518 flesch = 38 summary = In respect to the role of viruses in the pathogenesis of acute and chronic airway disease in children, it is of utmost importance that we gain a proper understanding of the underlying mechanisms involved in order to design effective therapeutic and preventive strategies. Epithelial cells are key regulators of the innate immune response against viral infections (Garofalo and Haeberle, 2000) , producing a number of inflammatory mediators in response to RSV infection. In summary, in RSV lower respiratory tract infections, cytotoxic CD8ϩ T-cells are involved in viral clearance while the humoral response is required for the protection against reinfection. The innate immune defense to viral respiratory tract infections consists of the mucosal layer, type 1 interferons, activated phagocytes, and NK-cells. A key question is whether the association with the development of asthma is merely an expression of increased susceptibility to both asthma and RSV-induced lower respiratory tract infections or whether true causality is involved. cache = ./cache/cord-007796-zggk0x2q.txt txt = ./txt/cord-007796-zggk0x2q.txt === reduce.pl bib === === reduce.pl bib === id = cord-011436-ud35mf5l author = Li, Yingying title = Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation date = 2020-04-06 pages = extension = .txt mime = text/plain words = 7446 sentences = 451 flesch = 56 summary = It was also found that rRABVs expressing IFN-λ could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. To further characterize the role of IFN-λ in RABV infection in the mouse model, recombinant RABVs (rRABVs) expressing murine IFN-λ2 or IFN-λ3, designated as rB2c-IFNλ2 and rB2c-IFNλ3 respectively, were constructed as shown in Figure 2A , and rescued as described previously [27] . To further investigate whether IFN-λ restricts RABV infection in vivo, groups of five-week-old female BALB/c mice were mock-infected with DMEM or inoculated with B2c, rB2c-IFNλ2, or rB2c-IFNλ3 by different routes. Expression of neuronal CXCL10 induced by rabies virus infection initiates infiltration of inflammatory cells, production of chemokines and cytokines, and enhancement of blood-brain barrier permeability cache = ./cache/cord-011436-ud35mf5l.txt txt = ./txt/cord-011436-ud35mf5l.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-017785-zwnkrs23 author = Baker, Michelle L. title = Mammalia: Chiroptera: Immunology of Bats date = 2018-03-10 pages = extension = .txt mime = text/plain words = 9426 sentences = 450 flesch = 46 summary = The role of bats as natural reservoirs of a variety of high-profile viruses that are highly pathogenic in other susceptible species yet cause no clinical disease in bats has led to a resurgence of interest in their immune systems. RNAseq studies on tissues and cells from a variety of different species of bats have provided evidence that bats have nearly all of the major components of the immune system that are present in other mammals, including receptors and molecules associated with innate and adaptive immunity and microRNAs (Papenfuss et al. Responses to antigens such as ϕX174 bacteriophage and sheep red blood cells have demonstrated that the generation of neutralizing antibodies is delayed in the big brown bat, the pteropid bat, and the Indian flying fox (Pteropus giganteus) (Hatten et al. cache = ./cache/cord-017785-zwnkrs23.txt txt = ./txt/cord-017785-zwnkrs23.txt === reduce.pl bib === === reduce.pl bib === id = cord-021872-rhi7hi9m author = Wilkes, Rebecca P. title = Update on Antiviral Therapies date = 2015-12-04 pages = extension = .txt mime = text/plain words = 9933 sentences = 524 flesch = 47 summary = Topical antiviral therapy has been mainly used for herpetic ocular disease, but studies have evaluated a systemic antiviral compound (famciclovir) for treatment of multiple clinical syndromes associated with FHV-1 infections. 7 A related drug, (R)-9-(2-phosphonylmethoxypropyl)-2,6diaminopurine (PMPDAP), has been shown previously to be a potent inhibitor of FIV replication in cell culture and has reduced the viral load in three of four cats experimentally infected with FIV when treated at 20 mg/kg SC three times per week for 6 weeks. 1 A prodrug of acyclovir, valacyclovir, was developed for increased bioavailability in humans, but use for FHV-1 treatment in experimentally infected cats induced fatal renal and hepatic necrosis and bone marrow suppression, and did not reduce viral shedding or clinical disease severity. 20 Even though this study did not mimic how cats with natural infection would be treated, results from a clinical case study suggested this drug is likely effective for treatment of clinical cases, though it was not blinded and placebo controlled. cache = ./cache/cord-021872-rhi7hi9m.txt txt = ./txt/cord-021872-rhi7hi9m.txt === reduce.pl bib === === reduce.pl bib === id = cord-008761-b36x05fn author = Billiau, A. title = The interferon system as a basis for antiviral therapy or prophylaxis date = 2012-02-26 pages = extension = .txt mime = text/plain words = 2464 sentences = 127 flesch = 45 summary = Possessing satisfactory answers to these questions is essential, not only to understand the natural role of the interferon system in virus disease but also to assess possible applications in medicine, in particular the use of interferons or interferoninducing substances as antiviral drugs. Interferon prepared from mouse cell lines infected with Newcastle disease virus is a mixture of a and B (6) . The main difference between these products and their natural-source-derived counterparts is that they contain only a single subtype, namely a2' While it is known that different subtypes of HuIFN-~ may differ in their antiviral potency depending on the cells on which they are tested, it is not yet known whether this has any repercussion for the clinical effects. Although these side-chains do not playa significant role in the effects of the IFN-S on cells, the pharmacokinetic behavior of this rDd-IFN-S was found to be rather different from that of natural fibroblast-derived interferon (8) . cache = ./cache/cord-008761-b36x05fn.txt txt = ./txt/cord-008761-b36x05fn.txt === reduce.pl bib === === reduce.pl bib === id = cord-022631-s4n24xij author = Jonsson, M. V. title = Germinal Centres in Primary Sjögren's Syndrome Indicate a Certain Clinical Immunological Phenotype date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16905 sentences = 873 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-022631-s4n24xij.txt txt = ./txt/cord-022631-s4n24xij.txt === reduce.pl bib === id = cord-004675-n8mlxe7p author = nan title = 2019 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date = 2019-02-26 pages = extension = .txt mime = text/plain words = 86427 sentences = 5050 flesch = 46 summary = However, the mean infusion rate per site was similar between patients aged <18 years ( XMEN disease (X-linked Immunodeficency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a primary immune deficiency caused by mutations in MAGT1 and characterized by chronic infection with Epstein-Barr virus (EBV), EBV-driven lymphoma, CD4 T-cell lymphopenia, and dysgammaglobulinemia. We present the case of a 1-year old Hispanic infant with a pathogenic variant in MAGT1 gene that clinically manifested with early Pneumocystis jirovecii and cytomegalovirus (CMV) interstitial pneumonia, and EBV chronic infection with good response to intravenous immunoglobulins supplementation without hematopoietic stem cell transplantation or gene therapy. Chief, Laboratory of Clinical Immunology and Microbiology, IDGS, DIR, NIAID, NIH, Bethesda, MD, USA Hypomorphic Recombination Activating Gene 1 (RAG1) mutations result in residual T-and B-cell development in both humans and mice and have been found in patients presenting with delayed-onset combined immune deficiency with granulomas and/or autoimmunity (CID-G/AI). cache = ./cache/cord-004675-n8mlxe7p.txt txt = ./txt/cord-004675-n8mlxe7p.txt === reduce.pl bib === === reduce.pl bib === id = cord-016343-wc3i54fc author = Frese, Michael title = Interferon-Induced Effector Proteins and Hepatitis C Virus Replication date = 2008 pages = extension = .txt mime = text/plain words = 10097 sentences = 503 flesch = 45 summary = RdRp, RNA-dependent RNA polymerase; IRES, internal ribosome entry site; 5BSL3.2, stem loop 3.2 within the coding sequence of NS5B normally result in the production of type I IFNs and the subsequent expression of IFN-induced effector proteins, which in turn would establish an antiviral state in the IFN-producing cell itself and in neighboring cells. Since MxA has the ability to efficiently inhibit a variety of different RNA viruses, MxA was the first IFN-induced effector protein to be analyzed for its antiviral activity in the HCV replicon system (Frese et al., 2001) . Rather indirect evidence that the OAS/RNase L pathway may indeed target HCV replication/translation was recently provided by Taguchi and co-workers, who reported that the N-terminal portion of NS5A (amino acids 1 to 148), which lacks the so-called PKR-binding domain, binds to OAS proteins and there by counteract the antiviral activity of IFN-α (Taguchi et al., 2004) . cache = ./cache/cord-016343-wc3i54fc.txt txt = ./txt/cord-016343-wc3i54fc.txt === reduce.pl bib === id = cord-023033-tgt69ir6 author = nan title = Poster Session (pp. 78A–178A) date = 2006-02-10 pages = extension = .txt mime = text/plain words = 16102 sentences = 855 flesch = 45 summary = Methods: We performed a retrospective analysis comparing outcomes, and the incidence, timing, and severity of histologic recurrence of HCV following transplantation in patients who underwent living donor liver transplant compared to recipients of cadaveric organs. Local liver immune responses are thought to play a major role in chronic autoimmune diseases directed at biliary epithelium.Using the apical sodium dependent bile acid transporter (ASBT) promoter to drive biliary epithelial cell -specific expression of a membrane form of ovalbumin (OVA), we have previously developed OVA-BIL transgenic mice. Thus, our AIM was to ascertain whether Kupffer cells express death ligands and contribute to hepatocyte apoptosis and liver fibrosis in the bile duct ligated mouse, an animal model of cholestasis. Control experiments confirmed that Y2 protein inhibited IFNa-induced ISRE-mediated signaling in Huh-T7 cells; relative luciferase activity was reduced from 653 (pH771 IFNP nAb increased HCV core Ag replication by 42% and 23% compared to no treatment (p=O.O1). cache = ./cache/cord-023033-tgt69ir6.txt txt = ./txt/cord-023033-tgt69ir6.txt === reduce.pl bib === id = cord-013481-3zwq67do author = Guo, Kejun title = Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis date = 2020-10-16 pages = extension = .txt mime = text/plain words = 9552 sentences = 494 flesch = 51 summary = The Type I Interferons (IFN-Is) are innate antiviral cytokines that include 12 different IFNα subtypes and IFNβ that signal through the IFN-I receptor (IFNAR), inducing hundreds of IFN-stimulated genes (ISGs) that comprise the 'interferome'. Since IFNβ, and not IFNα, is upregulated during chronic HIV-1 infection in the gut, we compared core ISGs and IFNβ-specific ISGs from colon pinch biopsies of HIV-1-uninfected (n = 13) versus ageand gender-matched, antiretroviral-therapy naïve persons with HIV-1 (PWH; n = 19). We recently reported that during chronic, untreated HIV-1 infection, IFN-I inducible antiretroviral genes APOBEC3G, BST2 and MX2, as well as IFNβ, but not IFNα, were expressed to significantly higher levels when compared to HIV-1 uninfected individuals [38] . These data suggest that increased IFNβ in the gut of chronic PWH may drive genes associated with sustained ISG expression, antigen processing, T cell activation, inflammation and immune exhaustion. cache = ./cache/cord-013481-3zwq67do.txt txt = ./txt/cord-013481-3zwq67do.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-023388-btbf6wkg author = Hoffmann, H. J. title = Decrease in Fine T‐cell Subset ratio MT2/MT1 During Steroid Reduction of Asthmatic Patients date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16918 sentences = 871 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023388-btbf6wkg.txt txt = ./txt/cord-023388-btbf6wkg.txt === reduce.pl bib === === reduce.pl bib === id = cord-023391-bq5w3jk9 author = Utermöhlen, O. title = Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16856 sentences = 870 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023391-bq5w3jk9.txt txt = ./txt/cord-023391-bq5w3jk9.txt === reduce.pl bib === === reduce.pl bib === id = cord-023387-tyeh14wz author = Hvas, C. L. title = Probiotic Bacteria Induce Regulatory Cytokine Production via Dendritic Cells date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16893 sentences = 881 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023387-tyeh14wz.txt txt = ./txt/cord-023387-tyeh14wz.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-017184-1ewi3dka author = nan title = Primary Immunodeficiencies date = 2008 pages = extension = .txt mime = text/plain words = 44492 sentences = 2035 flesch = 45 summary = In this disease, microorganism phagocytosis by polymorphonuclear (PMN) leukocytes appears annulled, and the patient is subject to severe infections supported by capsular bacteria: the deficiency, described in association with severe and recurrent infantile infections [175, 485, 487] , depends on the lack of mannose-binding lectin (MBL) [487] , its Primary Immunodeficiencies a possible atopy dependence on IgA underproduction rather than on IgE hyperproduction ( Fig. 4.1 ): in children with levels of IgA at the minimum normal level, and followed from birth until the age of 18-23 months, a greater severity of atopic manifestations and an increased cumulative incidence of asthma, AD and otitis media with effusion (OME) were observed compared to controls. cache = ./cache/cord-017184-1ewi3dka.txt txt = ./txt/cord-017184-1ewi3dka.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-023306-3gdfo6vd author = nan title = TSANZ Oral Abstracts date = 2010-03-01 pages = extension = .txt mime = text/plain words = 23387 sentences = 1370 flesch = 54 summary = Conflict of Interest No. Purpose We examined age trends in the distribution of stage at diagnosis in patients presenting with non-small cell lung cancer (NSCLC) at tertiary hospitals. Methods Eleven healthy male subjects, aged 28(8) (SD) years completed separate visits with (a) no restriction and (b) chest wall strapping to reduce FVC by 30 (7) Introduction Glossopharyngeal breathing (GPB) is used by competitive breath-hold divers to increase lung gas content above TLC to improve performance. Our DC culture results showed that both MHC-I and MHC-II expression on DCs from COPD were significantly down regulated compare to healthy controls, which could affect MHC restricted Ag presentation, and lead to a failure to activate responder T cells. cache = ./cache/cord-023306-3gdfo6vd.txt txt = ./txt/cord-023306-3gdfo6vd.txt === reduce.pl bib === id = cord-023392-axd0901z author = Hansen, T. K. title = Association between Mannose‐Binding Lectin and Vascular Complications in Type 1 Diabetes date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16944 sentences = 875 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023392-axd0901z.txt txt = ./txt/cord-023392-axd0901z.txt === reduce.pl bib === id = cord-023394-ptfjxpo6 author = Isa, A. title = Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16904 sentences = 872 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023394-ptfjxpo6.txt txt = ./txt/cord-023394-ptfjxpo6.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-023585-n3lr9z3u author = Phillpotts, Robert title = Interferon prophylaxis of the common cold date = 2003-01-06 pages = extension = .txt mime = text/plain words = 1970 sentences = 116 flesch = 55 summary = Robert Phillpotts describes the mechanism of interferon action and the future hopes and developments for its use in preventing colds. l~'obert Phillpotts describe~ the mechanism of interferon action and the future hopes and developments for its use in preventing colds. Interferon appears to be the ideal antiviral drug for use in preventing colds; it is extremely potent, and active against a wide range of viruses. intranasal interferon prevents colds In an initial experiment at the Common Cold Unit in Wiltshire, UK, intranasal administration of partially purified human leucocyte interferon to volunteers was shown to prevent colds caused by rhinovirus type 4 (Ref. 5). This question was answered in a further experiment carried out in 1982, in which HulFN a, purified to virtual homogeneity on a monoclonal antibody affinity column was shown to prevent colds caused by another rhinovirus, type 9 (Ref. 6). cache = ./cache/cord-023585-n3lr9z3u.txt txt = ./txt/cord-023585-n3lr9z3u.txt === reduce.pl bib === id = cord-023417-by18aczt author = Vilhelmsson, M. title = The Malassezia sympodialis Allergen Mala s 11 with Sequence Similarity to Manganese Superoxide Dismutase Induces Maturation and Production of Inflammatory Cytokines in Human Dendritic Cells date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16931 sentences = 868 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023417-by18aczt.txt txt = ./txt/cord-023417-by18aczt.txt === reduce.pl bib === id = cord-023143-fcno330z author = nan title = Molecular aspects of viral immunity date = 2004-02-19 pages = extension = .txt mime = text/plain words = 43425 sentences = 2056 flesch = 47 summary = Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells. cache = ./cache/cord-023143-fcno330z.txt txt = ./txt/cord-023143-fcno330z.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-023410-eblcf902 author = Kollgaard, T. M. title = Clonally Expanded CD8(+) T cells in Allogeneic Bone Marrow Transplantation date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16915 sentences = 872 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023410-eblcf902.txt txt = ./txt/cord-023410-eblcf902.txt === reduce.pl bib === === reduce.pl bib === id = cord-048489-ajafw966 author = Bozza, Fernando A title = Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity date = 2008-06-25 pages = extension = .txt mime = text/plain words = 4936 sentences = 261 flesch = 45 summary = title: Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity RESULTS: IL-1β, IFN-γ, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue) when compared to mild disease forms (mild dengue). Analysis of factors independently associated with dengue severity and other clinical manifestations was performed with GLM with logistic regression or Gaussian family. In order to avoid effects due to differences in the blood collection time, we compared mild and severe dengue patient groups using Mann-Whitney U Test, which showed no differences in the disease onset time at the moment of sample collection [see Additional file 1]. We studied the cytokine profile from Brazilian patients in order to compare severe and mild dengue cases during the acute phase of the disease. In the present study, the use of a multiplex analysis for cytokine plasma detection in patients with dengue could identify cytokine profiles associated with the disease severity. cache = ./cache/cord-048489-ajafw966.txt txt = ./txt/cord-048489-ajafw966.txt === reduce.pl bib === id = cord-023438-g0k0vvdc author = Krog, J. title = The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells, with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16880 sentences = 871 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023438-g0k0vvdc.txt txt = ./txt/cord-023438-g0k0vvdc.txt === reduce.pl bib === id = cord-023431-zjyrhlxn author = Sigmundsdóttir, H. title = Differential Effects of Interleukin‐12 and Interleukin‐10 on Superantigen‐Induced Expression of Cutaneous Lymphocyte‐Associated Antigen and αEβ7 Integrin (CD103) by CD8(+) T cells date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16867 sentences = 869 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023431-zjyrhlxn.txt txt = ./txt/cord-023431-zjyrhlxn.txt === reduce.pl bib === === reduce.pl bib === id = cord-023443-pvz7dll9 author = nan title = Abstracts for the Scandinavian Society for Immunology 35th Annual Meeting and 20th Summer School date = 2004-06-02 pages = extension = .txt mime = text/plain words = 16643 sentences = 857 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023443-pvz7dll9.txt txt = ./txt/cord-023443-pvz7dll9.txt === reduce.pl bib === === reduce.pl bib === id = cord-028945-p3hhd5ed author = Şahar, Esra Atalay title = Development of a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V and determination of its protective efficacy against acute toxoplasmosis date = 2020-07-10 pages = extension = .txt mime = text/plain words = 7383 sentences = 433 flesch = 55 summary = Thereafter, we developed a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V and administered to a murine model to determine its immunogenicity and protection efficiency against lethal toxoplasmosis. Hexavalent recombinant protein mixture (+) Montanide ISA 50 V vaccine induced significantly high levels of IgG1 and IgG2a at day 42 compared to the controls groups (P < 0.001, **). Overall, in mice administered with Hexavalent recombinant protein mixture (+) Montanide ISA 50 V, IgG2a and IgG1 levels showed a strong and balanced immune response. Overall, the Th1 part of the immune response elicited by hexavalent recombinant protein mixture (+) Montanide ISA 50 V induced significant levels of CD4 + and CD8 + T lymphocytes secreting IFN-γ and conferred significant protection in Swiss Outbred mice challenged with lethal dose of T. cache = ./cache/cord-028945-p3hhd5ed.txt txt = ./txt/cord-028945-p3hhd5ed.txt === reduce.pl bib === id = cord-025181-eg108wcd author = Zheng, Zhihang title = Establishment of Murine Infection Models with Biological Clones of Dengue Viruses Derived from a Single Clinical Viral Isolate date = 2020-05-25 pages = extension = .txt mime = text/plain words = 5919 sentences = 340 flesch = 59 summary = In this study, with biologically cloned viruses from a single clinical isolate, we have established two mouse models of DENV infection, one is severe lethal infection in immunocompromised mice, and the other resembles self-limited disease manifestations in Balb/c mice with transient blockage of type I IFN responses. Further, we compared the infectivity of these two viral variants in a self-limited infection model, in which type I IFN receptor of wild-type Balb/c mice had been transiently blocked before infection, and found only the virus strain exhibiting larger plaque size caused infectious viral particles in sera. We have recently developed a ZIKV infection model in Balb/c mice with transient blockage of type I IFN Fig. 2 Phylogenetic analysis of DENV-2 1D4-5-SP and DENV-2 8H2-7-LP with representative serotype-2 dengue viruses of different genotypes isolated from different geographical regions. cache = ./cache/cord-025181-eg108wcd.txt txt = ./txt/cord-025181-eg108wcd.txt === reduce.pl bib === id = cord-023419-lnmc6vv5 author = Steinhauer, C. title = High‐Throughput Proteomics on Antibody‐based Microarrays: the Importance of Probe and Surface Design date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16884 sentences = 871 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023419-lnmc6vv5.txt txt = ./txt/cord-023419-lnmc6vv5.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-015147-h0o0yqv8 author = nan title = Oral Communications and Posters date = 2014-09-12 pages = extension = .txt mime = text/plain words = 73711 sentences = 3862 flesch = 43 summary = Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis. cache = ./cache/cord-015147-h0o0yqv8.txt txt = ./txt/cord-015147-h0o0yqv8.txt === reduce.pl bib === id = cord-023439-r04y1j22 author = Hedegaard, C. J. title = The Role of Immune Complexes Consisting of Myelin Basic Protein (MBP), Anti‐MBP Antibodies and Complement in Promoting CD4(+) T‐cell Responses to MBP in Health and Multiple Sclerosis date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16932 sentences = 871 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. cache = ./cache/cord-023439-r04y1j22.txt txt = ./txt/cord-023439-r04y1j22.txt === reduce.pl bib === id = cord-023421-1d1gf7az author = Sønder, S. U. S. title = Monitoring Patients Treated with Type 1 Interferons: Antiviral versus MxA Induction Assays date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16866 sentences = 873 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023421-1d1gf7az.txt txt = ./txt/cord-023421-1d1gf7az.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-023429-x52gbklw author = Ruseva, M. title = Mannan‐Binding Lectin Inhibits Humoural Responses date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16880 sentences = 871 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023429-x52gbklw.txt txt = ./txt/cord-023429-x52gbklw.txt === reduce.pl bib === === reduce.pl bib === id = cord-252950-eiphxwmn author = Trouillet-Assant, Sophie title = Type I IFN immunoprofiling in COVID-19 patients date = 2020-04-29 pages = extension = .txt mime = text/plain words = 1555 sentences = 118 flesch = 53 summary = COVID patients in ICU present a high mortality rate and immunoprofiling reveals heterogeneous IFN-α2 production with about 20% of critically-ill patients unable to produce IFN-α2, highlighting the immune response heterogeneity and opening avenues for targeted therapies. 42 Capsule summary: 43 COVID patients in ICU present a high mortality rate and immunoprofiling reveals heterogeneous α2 production with about 20% of critically-ill patients unable to produce IFN-α2, highlighting the 45 immune response heterogeneity and opening avenues for targeted therapies. Various immunosuppressive drugs, including IL-6 blockers or JAK-STAT signaling inhibitors have been 56 suggested for the treatment of SARS-COV-2 infection 2 whereas additional clinical trials are evaluating 57 the use of recombinant interferon to foster host antiviral response. To date, IFN-I response has not been evaluated in COVID-19 60 patients and its contribution to the viral control and inflammation is unknown. We further explored a larger cohort of 26 critically ill COVID patients from one of the intensive care 75 unit (ICU) at Hospices Civils de Lyon (Lyon, France). cache = ./cache/cord-252950-eiphxwmn.txt txt = ./txt/cord-252950-eiphxwmn.txt === reduce.pl bib === id = cord-034467-jh9msz1c author = Olagoke, Olusola title = Koalas vaccinated against Koala retrovirus respond by producing increased levels of interferon-gamma date = 2020-10-31 pages = extension = .txt mime = text/plain words = 2209 sentences = 132 flesch = 49 summary = In the present study, we examined the expression of important koala cytokines, immune markers and host restrictions factors to determine their pre-and post-vaccination levels in northern koalas harbouring endogenous KoRV. Genes targeted included nine cytokines (CCL4L, Interleukin Open Access *Correspondence: oolagoke@usc.edu.au Genecology Research Centre, University of the Sunshine Coast, Sunshine Coast, QLD, Australia (IL)-1β, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-18 and Interferon gamma (IFN-γ), four host restriction factors (BST2, ISG15, RSAD2 and TRIM1) and two T-cell markers (CD4 and CD8β). In addition, none of the host restriction factors tested (BST2, ISG15, RSAD2 and TRIM1) had significant changes in their expression either at 4-or 8-weeks post-vaccination when compared to prevaccination levels. In this cohort of KoRV vaccinated and endogenously infected koalas, a small but significant increase in the expression of IFN-γ at both 4-and 8-weeks post-vaccination was observed, compared to pre-vaccination levels. Our study investigated the expression of four host restriction factors in koalas harbouring endogenous KoRV: BST2, ISG15, RSAD2 and TRIM1. cache = ./cache/cord-034467-jh9msz1c.txt txt = ./txt/cord-034467-jh9msz1c.txt === reduce.pl bib === id = cord-252528-rgnhfcbx author = Du, Fenghe title = COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness date = 2020-07-16 pages = extension = .txt mime = text/plain words = 8437 sentences = 359 flesch = 30 summary = • Anti-inflammatory therapies, including tocilizumab, chloroquine, and hydroxychloroquine, which can be promising treatment to control excessive cytokine release in severe COVID-19, have the potential to reduce the risk of vascular thrombotic events, but more clinical data are needed for optimum instruction of drug use and drug selection. By interpreting the pathological mechanisms, we aim to illustrate that excessive pro-inflammatory cytokine release and potential ACE2 down-regulation can promote the hypercoagulable state in severe COVID19 , and propose that the anti-inflammatory medications, as well as ACEI/ARB, can benefit severe COVID-19 patients by reducing the risk of vascular thrombotic events. cache = ./cache/cord-252528-rgnhfcbx.txt txt = ./txt/cord-252528-rgnhfcbx.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-029488-l11ufs6k author = Tomita, Kengo title = Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury date = 2020-07-21 pages = extension = .txt mime = text/plain words = 5094 sentences = 264 flesch = 45 summary = Expression levels of VEGF were significantly reduced in lung tissues from mice with both intranasal LPS administration and cecal ligation and puncture (CLP)-induced sepsis, which may stem from decreases in non-endothelial cells-dependent VEGF production in the lungs. In support of this assumption, stimulation with LPS and interferon-γ (IFN-γ) significantly increased VEGF in human pulmonary microvascular endothelial cells (HPMECs) at mRNA and protein levels. Taken together, our results indicate that VEGF can contribute to the development of non-cardiogenic lung edema in sepsis-associated ALI due to increased VEGF secretion from pulmonary vascular endothelial cells through multiple MAPK-dependent pathways. We thus examined whether expression of VEGF in human pulmonary microvascular endothelial cells is regulated by MAPKs. When HPMEC-ST1.6R cells were treated with PD98059, an inhibitor of MAPK kinase which is an ERK1/2 upstream activator, or SB203580, which is widely used as a specific inhibitor of p38 MAPK, the LPS/IFN-γinduced increase in VEGF protein levels was strongly blocked (Fig. 4b) . cache = ./cache/cord-029488-l11ufs6k.txt txt = ./txt/cord-029488-l11ufs6k.txt === reduce.pl bib === === reduce.pl bib === id = cord-032183-yqqqe325 author = Ning, Qin title = Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure) date = 2019-05-21 pages = extension = .txt mime = text/plain words = 32675 sentences = 1658 flesch = 43 summary = Patients awaiting liver transplantation because of HBV-related end-stage liver disease or liver cancer should be given nucleoside analogues with strong HBV inhibition and low drug-resistance, or nucleotides analogues combination treatment, in order to reduce viral load and prevent graft re-infection. The objective of antiviral treatment for HBV-ACLF is to reduce viral load at an appreciably high rate, thereby promoting reduction in hepatocyte cell death and improved survival outcomes by prevention of decompensation related multiorgan complications in this group of severely ill patients. Response-Guided Therapy 4006 study [126] suggested continuous treatment with LAM (10 years) delayed clinical progression in patients with chronic hepatitis and advanced fibrosis by significantly reducing the incidence of the risk of hepatocellular carcinoma and hepatic decompensation. cache = ./cache/cord-032183-yqqqe325.txt txt = ./txt/cord-032183-yqqqe325.txt === reduce.pl bib === id = cord-254492-42d77vxf author = Heaton, Steven M. title = Ubiquitin in the activation and attenuation of innate antiviral immunity date = 2016-01-11 pages = extension = .txt mime = text/plain words = 7382 sentences = 477 flesch = 39 summary = Here we review how hostand virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression. Methods for this include substrate molecular mimicry, binding and blocking E3-substrate pairs, expressing virally encoded E3s/DUbs, and hijacking host E3s/DUbs. Additionally, a novel mechanism involving ubiquitin chain packaging into nascent virions for subsequent redeployment Viral infection activates danger signals that are transmitted via the retinoic acid-inducible gene 1-like receptor (RLR), nucleotide-binding oligomerization domain-like receptor (NLR), and Toll-like receptor (TLR) protein signaling cascades. Here we review how host-and virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression. RNF125 forms part of this process, ligating K48-linked polyubiquitin chains to the activated CARD of RIG-I and MDA5, leading to proteasome-mediated degradation of both receptors and diminished IFN-I signaling. MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors cache = ./cache/cord-254492-42d77vxf.txt txt = ./txt/cord-254492-42d77vxf.txt === reduce.pl bib === id = cord-255709-tm3we5sd author = Mossel, Eric C. title = Synergistic Inhibition of Sars-Coronavirus Replication by Type I and Type II IFN date = 2006 pages = extension = .txt mime = text/plain words = 893 sentences = 60 flesch = 60 summary = It has been previously shown that treatment of cells with both type I and type II IFN produces an antiviral state greater in magnitude than can be explained by additive effects alone. Cytopathic effect (CPE) was extensive in vehicle-treated groups infected with either SARS-CoV strain at 120 hpi ( Fig. 2A and 2E) , as evident by the reduced monolayer staining with crystal violet. However, the CPE profile observed in Calu-3 cells suggests that the synergistic inhibitory effect on SARS-CoV replication by IFN-β and IFN-γ is not Vero E6 cell specific. It has been known for more than 25 years that treatment of cells with type I and type II IFN potentiates the antiviral response to levels greater than can be explained by simple additive effects. Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma cache = ./cache/cord-255709-tm3we5sd.txt txt = ./txt/cord-255709-tm3we5sd.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-256293-5lpe8hg2 author = Kageyama, Y. title = Jinhua Qinggan granule, a Chinese herbal medicine against COVID-19, induces rapid changes in the plasma levels of IL-6 and IFN-γ date = 2020-06-12 pages = extension = .txt mime = text/plain words = 1815 sentences = 137 flesch = 54 summary = title: Jinhua Qinggan granule, a Chinese herbal medicine against COVID-19, induces rapid changes in the plasma levels of IL-6 and IFN-γ However, in China, traditional Chinese herbal medicines have provided therapeutic benefit to patients with COVID-19. Jinhua Qinggan granule (JHQGG) is a Chinese multi-herbal formula previously developed for the treatment of H1N1 influenza and has been encouraged for patients clinically suspected of COVID-19 during medical observation. On the basis of its therapeutic efficacy for influenza, JHQGG has been recommended for patients clinically suspected of COVID-19 during medical observation. Notably, in blood cytokine analysis, the plasma levels of IL-6 and IFN-γ were significantly decreased and increased, respectively, compared with those in pre-administration (IL-6, 2.75 vs. The rapid immunomodulatory effects of JHQGG may be able to remedy the immune dysregulation observed in COVID-19 patients All rights reserved. Herbal medicine for the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of randomized controlled trials cache = ./cache/cord-256293-5lpe8hg2.txt txt = ./txt/cord-256293-5lpe8hg2.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-255997-oer5lxxr author = Onodi, Fanny title = SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date = 2020-07-10 pages = extension = .txt mime = text/plain words = 4209 sentences = 254 flesch = 53 summary = Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Interestingly, pDC responded to SARS-CoV-2 by a complete activation program, including diversification into effector subsets, production of type I and type III IFN, as well as inflammatory cytokines. We also showed that hydroxychloroquine, an antimalarial drug proposed for treatment of COVID-19 patients (Das et al., 2020; Mahévas et al., 2020) , inhibits SARS-CoV-2-induced pDC activation and IFN production in a dose-dependent manner. Following 24 hours of culture, we found that HCQ inhibited pDC diversification in response to SARS-CoV-2, which is similar to the decrease observed with Flu, used as a positive control ( Fig 4A) . cache = ./cache/cord-255997-oer5lxxr.txt txt = ./txt/cord-255997-oer5lxxr.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-252568-b8sbvy0g author = Marques Neto, Lázaro Moreira title = Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development date = 2017-03-08 pages = extension = .txt mime = text/plain words = 5317 sentences = 260 flesch = 39 summary = There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. However, many NPs have been shown to stimulate immune responses, including cell recruitment, activation of antigen (Ag)-presenting cells (APCs), and induction of cytokine and chemokine release. Among the vaccines targeting extracellular bacteria and toxin, two were formulated with lipopolysaccharide (LPS) in glycopeptide Ag. The use of glycoantigen and LPS can trigger an intense response through TLR4 and B cell receptor activation; the presence of gold NPs (AuNPs) may have minimal influence on this response. To understand the possible uses of MeNPs as platforms for vaccines against infectious diseases, analysis is needed of the impact of different physicochemical characteristics of NPs on the innate immune response (Figure 1) . cache = ./cache/cord-252568-b8sbvy0g.txt txt = ./txt/cord-252568-b8sbvy0g.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-256998-or73in8m author = Nguyen, Khue G. title = Localized Interleukin-12 for Cancer Immunotherapy date = 2020-10-15 pages = extension = .txt mime = text/plain words = 26912 sentences = 1416 flesch = 37 summary = Among the more notable responses in other early preclinical studies, nearly half of mice bearing established B16F10 melanomas experienced complete tumor regression following 2 weekly treatments with pIL-12+EP (124) . In preclinical studies, a single intratumoral injection of mRNA encoding murine IL-12 (mIL-12) increased IFNγ expression and genes associated with a Th1 response in MC38 tumor-bearing mice (190) . In a useful comparison against other cytokines, one study demonstrated that Ad-IFN-γ had no greater antitumor activity than an empty Ad vector, whereas AdmIL-12 induced complete regressions of P815 mastocytomas in >80% of treated mice (219) . Antitumor activity on xenografts of human lung tissues indicated that liposomal encapsulation is a promising approach capable of eliminating tumor cells and inducing lymphocyte infiltration 2 weeks after i.t. injection. Immunotherapy of established tumors in mice by intratumoral injection of an adenovirus vector harboring the human IL-2 cDNA: induction of CD8 + T-cell immunity and NK activity cache = ./cache/cord-256998-or73in8m.txt txt = ./txt/cord-256998-or73in8m.txt === reduce.pl bib === id = cord-000083-3p81yr4n author = nan title = Poster Exhibition date = 2009-01-31 pages = extension = .txt mime = text/plain words = 112815 sentences = 7542 flesch = 56 summary = R. China Background: The objective of this study was to evaluate the early virologic response for prediction of achievement of HBeAg seroconversion and hepatitis B virus (HBV) DNA negativity after two years of lamivudine treatment in chronic hepatitis B (CHB) patients. Methods: A total of 620 patients who tested positive for hepatitis B surface antigen and were referred to Chiba University Hospital between February 1985 and March 2008 were included in the study, and their following characteristics were analyzed: age, gender, the status of HBeAg, ALT, HBV-DNA level, and PLT. Methods: A total of 60 patients with chronic hepatitis B, 32 (53.3%) were HBeAg positive (group A) while 28(46.7%) were HBeAg negative (group B) were included in this study after meeting the following criteria: age 18 to 60 years, HBsAg positive for more than 6 months, serum HBV-DNA was >5 log(10) copies/mL and ALT more than two times the upper normal limit. cache = ./cache/cord-000083-3p81yr4n.txt txt = ./txt/cord-000083-3p81yr4n.txt === reduce.pl bib === === reduce.pl bib === id = cord-257220-fe2sacjj author = Butler, J. E. title = Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic date = 2014-07-01 pages = extension = .txt mime = text/plain words = 19650 sentences = 994 flesch = 44 summary = LDV elevates IgG levels in mice with little production of virus-specific antibodies [11, 21] , which is almost identical to what is seen in isolator piglets infected with PRRSV [22] (''The effect of age, rearing, complement and the role of mucosal immunity'' section). Polyclonal activation of B cells occurs in lymphoid organs from porcine reproductive and respiratory syndrome virus (PRRSV)-induced pigs The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells Antigen-specific B cell responses to porcine reproductive and respiratory syndrome virus infection Antibody production and blastogenesis response in pigs experimentally infected with porcine reproductive and respiratory syndrome virus Neutralizing antibody responses of pigs infected with natural GP5 N-glycan mutants of porcine reproductive and respiratory syndrome virus cache = ./cache/cord-257220-fe2sacjj.txt txt = ./txt/cord-257220-fe2sacjj.txt === reduce.pl bib === === reduce.pl bib === id = cord-255773-b4re5bky author = Zhang, Qingzhan title = Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1 date = 2016-01-14 pages = extension = .txt mime = text/plain words = 9880 sentences = 584 flesch = 52 summary = title: Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1 We showed that PEDV suppressed the type I interferon production and ISGs expression in these cells, and identified nsp1, nsp3, nsp7, nsp14, nsp15, nsp16, E, M, N and ORF3 as the viral IFN antagonists. The CBP degradation is a novel mechanism of coronavirus nsp1 for IFN suppression and our study provides a new insight into the immune modulation and evasion strategy of PEDV. MARC-145 cells have been used to study type I IFN signaling of porcine arterivirus (Kim et al., 2010; Overend et al., 2007; Patel et al., 2010) , and thus infection of these cells One μg of each of the cloned genes was transfected to HeLa cells in 12-well plates, and protein expression was determined by immunofluorescence (B) and cache = ./cache/cord-255773-b4re5bky.txt txt = ./txt/cord-255773-b4re5bky.txt === reduce.pl bib === === reduce.pl bib === id = cord-253862-jl1zhg13 author = Khalaf, Khalil title = SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date = 2020-10-06 pages = extension = .txt mime = text/plain words = 14595 sentences = 760 flesch = 45 summary = Although this novel virus is less severe than the first SARS-CoV outbreak, human-to-human transmission remains very high and the number of cases continues to rise exponentially in major urban areas, highlighting the urgent need to develop new containment, diagnostic, and treatment protocols. In the case of SARS-CoV-2, viral evasion of the innate immune system leads to an increase in cytokine production and late CD4+/CD8+ response, which then leads to pathogenic inflammation in patients with high viral loads. (ChiCTR2000029308), involving severe SARS-CoV-2 cases, compared lopinavir/ritonavir treatment with standard care alone, and they showed that the antivirals yielded no clinical benefits. In an open-label control study conducted by Cai et al., the antiviral activity of favipiravir + IFN-α was compared to that of lopinavir/ritonavir + IFN-α in patients with confirmed SARS-CoV-2 infection. cache = ./cache/cord-253862-jl1zhg13.txt txt = ./txt/cord-253862-jl1zhg13.txt === reduce.pl bib === id = cord-261028-sxux2ujo author = Vatner, Ralph E. title = STING, DCs and the link between innate and adaptive tumor immunity date = 2017-12-20 pages = extension = .txt mime = text/plain words = 10018 sentences = 475 flesch = 44 summary = Dendritic cells (DCs) are a heterogeneous population of professional antigen-presenting cells (APCs) from hematopoietic origin that serve as a key link between the innate and adaptive immune systems, and are the lynchpin in generating anti-tumor immunity (Steinman and Idoyaga, 2010) . More recently, type I IFN production and signaling through the STING pathway has been identified as having an essential role in the development of anti-tumor immunity in response to tumor derived DNA. DNA sensing by STING is the upstream link that triggers type I IFN production by DCs and facilitates effective cross-priming of tumor specific CD8+ T cells. This DNA is likely derived from stressed and dying cancer cells, and is introduced into the DC cytosol through a yet unknown mechanism where it binds to cGAS, which initiates STING mediated type I IFN transcription (Fig. 2) . cache = ./cache/cord-261028-sxux2ujo.txt txt = ./txt/cord-261028-sxux2ujo.txt === reduce.pl bib === === reduce.pl bib === id = cord-263200-ntq1f4ix author = Mao, He-Ting title = HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex date = 2016-05-21 pages = extension = .txt mime = text/plain words = 4451 sentences = 320 flesch = 54 summary = To initiate an effective antiviral response, RNA viruses are recognized by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs), and then trigger multiple signaling pathways to promote the production of proinflammatory cytokines, including type I IFNs [1] [2] [3] [4] . In this study, we demonstrate for the first time that HACE1 contributes to negative regulation of the virus-induced type I IFN signaling via disrupting the MAVS-TRAF3 complex. HACE1 suppressed virus-induced type I IFN signaling independently of its ubiquitin E3 ligase activity. By a small-scale screening of unknown ubiquitin E3 ligases in the regulation of virus-induced type I IFN signaling by the dual-luciferase reporter, we identified HACE1 as a potential negative regulator in this pathway. By a small-scale screening of unknown ubiquitin E3 ligases in the regulation of virus-induced type I IFN signaling by the dual-luciferase reporter, we identified HACE1 as a potential negative regulator in this pathway. cache = ./cache/cord-263200-ntq1f4ix.txt txt = ./txt/cord-263200-ntq1f4ix.txt === reduce.pl bib === id = cord-256325-q70rky3r author = Stewart, Cameron R. title = A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease date = 2017-07-04 pages = extension = .txt mime = text/plain words = 8310 sentences = 409 flesch = 43 summary = title: A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease Here we largely focus on findings from two recent RNAi screens to identify protein-coding genes and host-encoded microRNAs impacting the henipavirus infection cycle in human cells. X-ray data have suggested that the methylation of rRNA requires the formation of this complex with involvement of four fibrillarin molecules interacting with different regions of the target rRNAs. The yeast equivalent of fibrillarin, NOP1, has been more extensively studied than the human counterpart but fibrillarin is a well-conserved protein in most organisms, reinforcing the notion that all post-transcriptional processes involving fibrillarin such as chemical modification (methylation) of rRNA, pre-rRNA cleavage and ribosome assembly are essential for proper cellular functioning (Rodriguez-Corona et al. Deffrasnes and colleagues showed that siRNA-mediated knockdown of fibrillarin expression dramatically reduced HeV protein production and viral genome replication but did not impact viral fusion, and that fibrillarin catalytic activity was essential to henipavirus infection. cache = ./cache/cord-256325-q70rky3r.txt txt = ./txt/cord-256325-q70rky3r.txt === reduce.pl bib === === reduce.pl bib === id = cord-258286-lodjcj8c author = Zhang, Xuming title = Expression of Interferon-γ by a Coronavirus Defective-Interfering RNA Vector and Its Effect on Viral Replication, Spread, and Pathogenicity date = 1997-07-07 pages = extension = .txt mime = text/plain words = 5866 sentences = 296 flesch = 54 summary = Previous studies have shown that immunocoma large plaque variant derived from the parental JHM petent mice infected with MHV exhibited increased exstrain (Stohlman et al., 1982) ; the small plaque variant pression of a number of cytokines, including IL-1, IL-6, DS (Stohlman et al., 1982) ; the neutralization-escape mu-TNF-a, and IFN-g, in the CNS at the time of viral cleartant 2.2-V-1 (Fleming et al., 1987; Wang et al., 1992) , and ance (Pearce et al., 1994) . The expressed IFNg exhibited antiviral activity, prevented virus spread in layers of DBT cells grown at approximately 70% confluence in 60-mm petri dishes were infected with MHV at vitro, and altered viral pathogenesis in mice. Expression of IFN-g using an MHV DI RNA vector cell metabolism prior to infection or it may be that interferon acts at an early stage of viral replication. cache = ./cache/cord-258286-lodjcj8c.txt txt = ./txt/cord-258286-lodjcj8c.txt === reduce.pl bib === id = cord-262673-j2ot35lt author = Ahmed-Hassan, Hanaa title = Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections date = 2020-08-18 pages = extension = .txt mime = text/plain words = 8591 sentences = 472 flesch = 41 summary = Furthermore, respiratory epithelial cells and lung macrophages are capable of secreting a broad range of chemokines like IL-8, Macrophage inflammatory protein-1 (MIP-1), RANTES and cytokines including TNF-α, IL-6, IL-1β that influence the types of immune cells being recruited to the area in response to acute viral infections (177, 178) . Both Influenza and SARS virus can induce acute lung injury (ALI) which is accompanied by high levels of C5a, leading to the influx and activation of innate immune cells (199) (Figure 1) . Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus Middle East respiratory syndrome coronavirus shows poor replication but significant induction of antiviral responses in human monocytederived macrophages and dendritic cells Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells cache = ./cache/cord-262673-j2ot35lt.txt txt = ./txt/cord-262673-j2ot35lt.txt === reduce.pl bib === === reduce.pl bib === id = cord-258691-cd83w9o6 author = Whitman, Lucia title = IFN-γ-mediated suppression of coronavirus replication in glial-committed progenitor cells date = 2009-02-01 pages = extension = .txt mime = text/plain words = 4938 sentences = 257 flesch = 40 summary = IFN-γ-mediated control of JHMV replication is dampened in glial cultures derived from the neural progenitor cells of type I receptor knock-out mice. These data indicate that JHMV is capable of infecting glial cells generated from neural progenitor cells and that IFN-γ-mediated control of viral replication is dependent, in part, on type I IFN secretion. In the present study, we demonstrate that primary cultures of glia derived from neural progenitor cells are susceptible to JHMV infection and support viral replication. Therefore, these findings provide, to our knowledge, the first demonstration that glia-committed cells derived from neural precursors are susceptible to JHMV infection as well as identify a potential mechanism responsible for controlling viral replication. These findings indicate that differentiated cells derived from neural progenitors are susceptible to JHMV infection and are capable of supporting replicating virus which results in extensive cytopathology. cache = ./cache/cord-258691-cd83w9o6.txt txt = ./txt/cord-258691-cd83w9o6.txt === reduce.pl bib === === reduce.pl bib === id = cord-259669-fod4xkd7 author = Summerfield, Artur title = The porcine dendritic cell family date = 2008-06-06 pages = extension = .txt mime = text/plain words = 9379 sentences = 489 flesch = 46 summary = Being strategically located at sites of pathogen entry, such as mucosal surfaces and Considering the pivotal roles played by dendritic cells (DCs) in both innate and adaptive immune responses, advances in the field of porcine immunology DC biology have recently progressed rapidly. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. Altogether, the co-expression of CD172a and CD1 along with relatively high levels of both CD80/86 and MHC class II represent phenotypic characteristics of porcine MoDC but no marker clearly differentiating them from monocyte-derived macrophages has been identified. cache = ./cache/cord-259669-fod4xkd7.txt txt = ./txt/cord-259669-fod4xkd7.txt === reduce.pl bib === id = cord-259748-x7dq1sy4 author = Wan, Dongshan title = Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response date = 2020-04-28 pages = extension = .txt mime = text/plain words = 14147 sentences = 850 flesch = 41 summary = Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immune-surveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. In 2008, several research teams discovered a new protein on the endoplasmic reticulum (ER) which can be activated by immune-stimulatory DNA (ISD) and initiate type-I interferon (IFN) responses, which was named "stimulator of interferon genes" (STING, also known as MITA, ERIS) (2) (3) (4) . Mitochondrial outer membrane permeabilization (MOMP) activation, which is executed by BCL-2-associated X protein (BAX) and BCL-2 antagonist or killer (BAK), is a highly controlled conserved process in regulated cell FIGURE 3 | Interaction of the cGAS-STING pathway with other DNA-sensing pathways and its role in cell survival. Human plasmacytoid dentritic cells elicit a Type I interferon response by sensing DNA via the cGAS-STING signaling pathway cache = ./cache/cord-259748-x7dq1sy4.txt txt = ./txt/cord-259748-x7dq1sy4.txt === reduce.pl bib === id = cord-261380-xms5su6w author = Rahmani, Hamid title = Interferon β-1b in treatment of severe COVID-19: a randomized clinical trial date = 2020-08-24 pages = extension = .txt mime = text/plain words = 2770 sentences = 170 flesch = 51 summary = Among an open-label, randomized clinical trial, adult patients (≥ 18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. According to the presence of this evidence, IFN β was considered as a promising option for the treatment of In this open-label, randomized clinical trial, efficacy and safety of IFN β-1b in the treatment of patients with severe CoVID-19 were assessed. This open-label, randomized clinical trial was designed to evaluate the efficacy and safety of IFN β-1b in the treatment of patients with CoVID19 Adult patients (≥ 18 years old) with positive PCR and clinical symptoms/signs of pneumonia (including dyspnea, cough and fever), peripheral oxygen saturation (SPO 2 ) ≤ 93 % in ambient air or arterial oxygen partial pressure to fractional inspired oxygen (PaO 2 /FiO 2 ) < 300 or SPO 2 /FiO 2 < 315 and lung involvement in chest imaging were included. cache = ./cache/cord-261380-xms5su6w.txt txt = ./txt/cord-261380-xms5su6w.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-270498-hh6h50t2 author = Tseng, Chin-Kai title = Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells date = 2017-09-19 pages = extension = .txt mime = text/plain words = 4954 sentences = 277 flesch = 47 summary = Celastrol-induced heme oxygenase 1 (HO-1) expression promoted antiviral interferon responses and inhibition of NS3/4A protease activity, thereby blocking HCV replication. These antiviral effects were abrogated by treatment with the HO-1-specific inhibitor SnMP or silencing of HO-1 expression by transfection of shRNA, which indicates that HO-1 induction contributes to the anti-HCV activity of celastrol. In this study, our data revealed that celastrol significantly inhibits HCV replication, and that the anti-HCV effect of celastrol was attenuated by the HO-1 specific inhibitor tin mesoporphyrin (SnMP) or HO-1 gene expression silencing. Celastrol-mediated HO-1 induction contributed to the anti-HCV action through inducing antiviral IFN response and inhibiting HCV NS3 protease activity. As shown in Fig. 7B , HO-1 RNA expression levels were induced by celastrol compared with non-celastrol treated cells and the JNK inhibitor SP600125 significantly reduced the HO-1 inductive effect of celastrol. In the present study, we found that a natural product celastrol could effectively inhibit HCV NS3/4A protease activity and enhance IFN-mediated antiviral gene expression through HO-1 induction (Figs. cache = ./cache/cord-270498-hh6h50t2.txt txt = ./txt/cord-270498-hh6h50t2.txt === reduce.pl bib === === reduce.pl bib === id = cord-270534-ebkwv4zo author = Bodmer, Bianca S. title = Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model date = 2018-06-11 pages = extension = .txt mime = text/plain words = 6539 sentences = 362 flesch = 53 summary = title: Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model One of these candidates, MV vac2 -MERS-S(H) (Malczyk et al., 2015) , is based on the measles virus (MV) vaccine platform technology (Mühlebach, 2017) , and encodes the MERS-CoV spike protein (S) as an additional antigen in the backbone of recombinant MV vac2 (del Valle et al., 2007) resembling vaccine strain Moraten that is authorized and in use in the US since 1968. (G) Secretion of IFN-γ after antigen-specific re-stimulation of splenocytes harvested 32 days post prime immunization and after co-culture with JAWSII (left) or DC2.4 (middle) dendritic cells transgenic for MERS-N (black) or untransduced controls (NC, white). To assess the capacity of the different MV vac2 -MERS-S(H) vaccine preparations to induce MERS-CoV S-specific cellular immune responses, splenocytes of mice, which had already been tested for humoral responses ( Fig. 2A) , were isolated and analyzed 49 days after immunization for antigen(Ag)-dependent IFN-γ secretion using ELISpot assay. cache = ./cache/cord-270534-ebkwv4zo.txt txt = ./txt/cord-270534-ebkwv4zo.txt === reduce.pl bib === id = cord-265005-e6rpryrh author = Tomasello, Elena title = Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types date = 2014-10-30 pages = extension = .txt mime = text/plain words = 18082 sentences = 948 flesch = 40 summary = We will discuss the expression patterns and functions of endosomal TLRs with regards to IFN production in uninfected specialized immune cell types, pDCs and XCR1 + DCs. Plasmacytoid DCs uniquely produce very large amounts of IFNs in response to in vitro stimulation with many viruses, without being infected (46) . Under these conditions, to promote health over disease, the benefits for the host of producing high circulating levels of IFNs in order to induce widespread cell-intrinsic anti-viral defenses might prevail over the deleterious effects that this could cause on certain cell types or tissues. Subcapsular sinus macrophages rapidly become infected by viruses incoming from the lymph and produce large amounts of IFNs. This altruistic suicide prevents virus dissemination to other adjacent cell types and promotes the induction of innate and adaptive anti-viral immunity (87) . cache = ./cache/cord-265005-e6rpryrh.txt txt = ./txt/cord-265005-e6rpryrh.txt === reduce.pl bib === === reduce.pl bib === id = cord-271970-i35pic5o author = Boris, Bonaventure title = A genome-wide CRISPR/Cas9 knock-out screen identifies the DEAD box RNA helicase DDX42 as a broad antiviral inhibitor date = 2020-10-28 pages = extension = .txt mime = text/plain words = 6320 sentences = 343 flesch = 52 summary = Depletion of endogenous DDX42 using siRNA or CRISPR/Cas9 knock-out increased HIV-1 infection, both in model cell lines and in physiological targets of HIV-1, primary CD4+ T cells and monocyte-derived macrophages (MDMs), and irrespectively of the IFN treatment. Deep sequencing analysis of the GeCKO cell populations showed more than 94% coverage for both libraries (≥ 10 reads for 61,598 and 54,609 sgRNA-coding sequences out of GeCKO populations were subjected to type 1 IFN treatment in order to induce the antiviral state and, 24h later, incubated with VSV-G-pseudotyped, HIV-1 based LVs coding for an antibiotic resistance cassette. In order to validate the effect of DDX42 KO on HIV-1 infection in another model cell line, two additional sgRNAs were designed (sgRNA-2 and -3) and used in parallel to the one identified in the GeCKO screen (sgDDX42-1) (Figure 2A ). cache = ./cache/cord-271970-i35pic5o.txt txt = ./txt/cord-271970-i35pic5o.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-265941-eff4le0g author = Eng, Vik Ven title = The diverse roles of RIP kinases in host-pathogen interactions date = 2020-08-26 pages = extension = .txt mime = text/plain words = 11836 sentences = 657 flesch = 34 summary = Nevertheless, the signal transduction that follows pathogen recognition elicits numerous defence mechanisms, including the induction of inflammatory cytokine, chemokine and interferon production, activation of programmed cell death pathways, and inevitably an adaptive immune response, all of which contribute to pathogen control and elimination [1] . As inhibition of necroptosis does not affect IAV control, while Mlkl-/-Fadd-/-mice exhibit marked susceptibility to IAV-induced lethality [78] , it signifies that RIPK1/3-mediated apoptosis is a major form of host protection against IAV infection. A number of studies have used purified pathogen components such as LPS to investigate the outcomes of RIPK1/3-mediated inflammasome signaling, which appear to be largely dependent on cell type, stimulus, and the availability or functional activity of certain host signaling proteins [65, [123] [124] [125] [126] [127] . Overall this suggests that RIPK2 plays an important role in both innate and adaptive immunity to infection [137, 151] , and that RIPK2 was mediating these responses via NOD1/2 and not directly via TLR activation [140] . cache = ./cache/cord-265941-eff4le0g.txt txt = ./txt/cord-265941-eff4le0g.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-271114-hv3gwvdi author = Allam, Gamal title = Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms date = 2015-04-22 pages = extension = .txt mime = text/plain words = 5564 sentences = 313 flesch = 52 summary = The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. Therefore, the primary aim of the current study was to investigate SNPs in the IL-1β -31 T/C (rs1143643), IL-6 -174 G/C (rs1800795), TNF-α -308 G/A (rs1800629), and IFN-γ +874 A/T (rs2430561) genes for their possible association with susceptibility to EOS in Saudi newborn infants. Newborns with sepsis had significantly higher serum levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) compared to both suspected and sepsis-free control groups (overall p value < 0.001, Table 1 ). cache = ./cache/cord-271114-hv3gwvdi.txt txt = ./txt/cord-271114-hv3gwvdi.txt === reduce.pl bib === id = cord-007890-bie1veti author = nan title = ECC-4 Abstracts date = 2002-04-16 pages = extension = .txt mime = text/plain words = 85992 sentences = 5665 flesch = 50 summary = Effects of Interferon alpha plus ribavirine therapy on frequencies of HCV, HIV and CMV specific CD4-T-cell responses in peripheral blood of HIV/HCV coinfected patients after 6 months of treatment SoA9.5 Methods: Two groups of patients with chronic HCV infection were studied: 26 HIV coinfected progressors with antiretroviral therapy and 13 HIV-negative controls. In order to assess the local temporal trend of antibiotic sensitivity of the most common urinary tract bacterial pathogen, all urine-cultured Escherichia coli isolates were reviewed as to susceptibility profile, and specimen source (community-versus hospital-acquired infection). Methods: A total of 87 penicillin resistant clinical strains isolated from patients at Hacettepe Children's Hospital, Ankara, Turkey between 1999 and 2001 were tested for their in vitro susceptibility to various antibiotics that are commonly used in the treatment of respiratory tract infections. cache = ./cache/cord-007890-bie1veti.txt txt = ./txt/cord-007890-bie1veti.txt === reduce.pl bib === id = cord-275413-e2rhioty author = Rowland, Raymond R.R. title = The interaction between PRRSV and the late gestation pig fetus date = 2010-09-09 pages = extension = .txt mime = text/plain words = 6183 sentences = 344 flesch = 50 summary = The purpose of this study was to characterize the interaction between PRRSV and the pig fetus by (1) identifying sites of virus replication, (2) measuring immune and inflammatory cytokines in different compartments, and (3) evaluating the response of lymph nodes. Maternal, accessory and fetal tissues were collected and stored in formalin for histological staining and immunohistochemistry (IHC), or storage in RNAlater (Ambion) for RT-PCR of cytokine mRNAs. PRRSV-specific antibody was measured in sera using the HerdCheck ® PRRS ELISA (IDEXX) and performed by personnel at Kansas State University Veterinary Diagnostic Laboratory. As shown in Fig. 4A , IFN-␥ and TNF-␣ PCR products were not detected in lung, lymph node or placenta from the non-infected fetuses. To determine if cytokine gene expression was the direct result of PRRSV infection, RT-PCR for IFN-␥ and TNF-␣ was performed on the same tissues from fetuses of infected dam no. cache = ./cache/cord-275413-e2rhioty.txt txt = ./txt/cord-275413-e2rhioty.txt === reduce.pl bib === id = cord-270380-1me7ugkg author = Wang, Xiaona title = Cloning, Prokaryotic Soluble Expression, and Analysis of Antiviral Activity of Two Novel Feline IFN-ω Proteins date = 2020-03-19 pages = extension = .txt mime = text/plain words = 5963 sentences = 300 flesch = 46 summary = Both proteins exhibited effective anti-vesicular stomatitis virus (VSV) activity in Vero, F81 (feline kidney cell), Madin–Darby bovine kidney (MDBK), Madin–Darby canine kidney (MDCK), and porcine kidney (PK-15) cells, showing broader cross-species antiviral activity than the INTERCAT IFN antiviral drug. Furthermore, the recombinant feIFN-ωa and feIFN-ωb proteins demonstrated antiviral activity against VSV, feline coronavirus (FCoV), canine parvovirus (CPV), bovine viral diarrhea virus (BVDV), and porcine epidemic diarrhea virus (PEDV), indicating better broad-spectrum antiviral activity than the INTERCAT IFN. As shown in Figure 6 , the purified recombinant feIFN-ωa and feIFN-ωb proteins showed antiviral activity in both homologous animal cells (F81 cells) and heterologous animal cells (Vero, MDCK, MDBK, and PK-15 cells) in vitro. Our data showed that purified recombinant feIFN-ωa and feIFN-ωb had broad-spectrum antiviral activity in homologous and heterologous animal cells, suggesting they are candidates for the development of effective therapeutic agents to be used against viral infections in pet cats. cache = ./cache/cord-270380-1me7ugkg.txt txt = ./txt/cord-270380-1me7ugkg.txt === reduce.pl bib === === reduce.pl bib === id = cord-268419-j90daoiq author = Resende, Lucilene Aparecida title = Cytokine and nitric oxide patterns in dogs immunized with LBSap vaccine, before and after experimental challenge with Leishmania chagasi plus saliva of Lutzomyia longipalpis date = 2013-12-06 pages = extension = .txt mime = text/plain words = 7182 sentences = 349 flesch = 53 summary = chagasi challenge infection, PBMCs from LBSap vaccinated dogs produced more IL-12, IFN-γ and concomitant nitric oxide (NO) when stimulated with Leishmania antigens as compared to PBMCs from respective control groups (saponin, LBtreated, or non-treated control dogs). chagasi challenge infection, PBMCs from LBSap vaccinated dogs produced more IL-12, IFN-␥ and concomitant nitric oxide (NO) when stimulated with Leishmania antigens as compared to PBMCs from respective control groups (saponin, LB-treated, or non-treated control dogs). Thus, the profile of different cytokines (IL-4, IL-10, TGF-␤, IL-12, IFN-␥, and tumor necrosis factor [TNF]-␣) and nitric oxide (NO) in supernatants of peripheral blood mononuclear cell (PBMC) cultures were evaluated before the first immunization (T 0 ), 15 days after completion of the vaccine protocol (T 3 ), and at time points 90 (T 90 ) and 885 (T 885 ) days after experimental L. cache = ./cache/cord-268419-j90daoiq.txt txt = ./txt/cord-268419-j90daoiq.txt === reduce.pl bib === id = cord-272237-gnno6elo author = Wang, Ziran title = A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids date = 2020-07-31 pages = extension = .txt mime = text/plain words = 4472 sentences = 241 flesch = 53 summary = A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). cache = ./cache/cord-272237-gnno6elo.txt txt = ./txt/cord-272237-gnno6elo.txt === reduce.pl bib === === reduce.pl bib === id = cord-277487-jgbjxgh1 author = Graham, Simon P. title = Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date = 2020-06-20 pages = extension = .txt mime = text/plain words = 5057 sentences = 242 flesch = 53 summary = Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. Analysis of SARS-CoV-2 S protein-specific murine splenocyte responses by IFNγ ELISpot assay showed no statistically significant difference between the prime-only and primeboost vaccination regimens, in either strain of mouse ( Figure 1A ). IFN-γ ELISpot analysis of porcine peripheral blood mononuclear cells (PBMC) showed responses on 42 dpv (2 weeks after boost) that were significantly greater in the prime-boost pigs compared to prime-only animals (p < 0.05; Figure 1C ). : SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 primeonly and prime-boost vaccination regimens in mice and pigs. cache = ./cache/cord-277487-jgbjxgh1.txt txt = ./txt/cord-277487-jgbjxgh1.txt === reduce.pl bib === === reduce.pl bib === id = cord-274816-6xpma224 author = Onal, Merih title = Can secondary lymphoid organs exert a favorable effect on the mild course of COVID-19 in children? date = 2020-10-27 pages = extension = .txt mime = text/plain words = 1426 sentences = 76 flesch = 43 summary = Palatine and pharyngeal tonsils are important organs of the immune system, and they protect the body from pathogens invading the upper respiratory tract, especially in young children [8] . In a study on patients with hypertrophic adenoid tissue, recurrent upper and lower respiratory tract infections were demonstrated along with high serum myeloperoxidase levels (indicating neutrophil activation), increased serum eosinophilic cationic protein levels (indicating eosinophil activation) and high CD 163 glycoprotein levels (indicating monocyte/macrophage activation) [15] . It is known that human tonsils are immunologically reactive lymphoid organs carrying out humoral and cellular immunity functions as a response to various antigens and displaying B and T cell activity [16] . In the same study, although a difference was expected in tonsillar hypertrophy and recurrent tonsillitis groups in terms of the levels of interferons (IFN-a, IFN-b, IFN-c, IL-28, IL-29) , which are cytokines with antiviral activity and whose expression is induced by viral infection, not detected. cache = ./cache/cord-274816-6xpma224.txt txt = ./txt/cord-274816-6xpma224.txt === reduce.pl bib === id = cord-276350-lcl9jn35 author = Acharya, Dhiraj title = Dysregulation of type I interferon responses in COVID-19 date = 2020-05-26 pages = extension = .txt mime = text/plain words = 1608 sentences = 83 flesch = 40 summary = In a mouse model of SARS-CoV infection, local IFN responses in the lungs were delayed relative to peak viral replication, which impeded virus clearance and was associated with the development of CRS 5 . By contrast, IFNAR inhibition enhanced the recruitment of neutrophils to the lungs in MERS-CoV-infected mice, leading to elevated production of pro-inflammatory cytokines 6 . While patients with severe COVID-19 showed profound depletion and functional exhaustion of NK cells 8 , it is unclear whether this NK cell dysfunction is due to dysregulation of IFN responses. It is thus tempting to speculate that the deficient or dysregulated IFN responses elicited by SARS-CoV-2 infection may influence the generation of T reg cells during the recovery phase of COVID-19. Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice cache = ./cache/cord-276350-lcl9jn35.txt txt = ./txt/cord-276350-lcl9jn35.txt === reduce.pl bib === id = cord-271250-ywb26cq6 author = Sarkar, Indranil title = Selection of adjuvants for vaccines targeting specific pathogens date = 2019-04-22 pages = extension = .txt mime = text/plain words = 11394 sentences = 542 flesch = 39 summary = In-depth understanding of the role of adjuvants in activating the innate immune system, combined with systems vaccinology approaches, have led to the development of next-generation, novel adjuvants that can be used in vaccines against challenging pathogens and in specific target populations. Intact MyD88 signaling in each of the three types of APCs (DCs, macrophages and B cells) is essential for robust activity of TLR ligand-based vaccine adjuvants (PorB, a TLR2 ligand and CpG, a TLR9 ligand) such as induction of in vivo cytokine responses, germinal center (GC) formation and antibody production [49] . A combination adjuvant consisting of poly(I:C), a host defense peptide and PCEP when delivered intranasally transiently induces production of chemokines and cytokines in murine respiratory tissues, which promotes infiltration and activation of DCs, macrophages, and neutrophils to generate improved mucosal and systemic immune responses [55] . cache = ./cache/cord-271250-ywb26cq6.txt txt = ./txt/cord-271250-ywb26cq6.txt === reduce.pl bib === === reduce.pl bib === id = cord-273050-reez33md author = Wang, Zhenling title = Type I IFN deficiency: an immunological characteristic of severe COVID-19 patients date = 2020-09-14 pages = extension = .txt mime = text/plain words = 1337 sentences = 85 flesch = 46 summary = reported that type I interferon (IFN) deficiency, could be a hallmark of severe coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compared with patients that had mild-to-moderate infection, the ISG score (based on the mean expression value of six ISGs defining a type I IFN signature) was significantly reduced in critical patients. By correlated analysis of viral loading with IFN-α production either on protein or on gene level, the authors suggest that the most severe cases of COVID-19 are featured by impaired IFN-α production. To further explore the transcription factors that may cause the excessive inflammatory response of COVID-19, the authors observed that upregulated genes in severe or critical patients mainly belonged to the NF-κB pathway by a kinetic analysis. Impaired type I IFN response featured immunological characteristics of severe COVID-19 patients, accompanied by lymphocytopenia, hypercytokinaemia, and high blood viral load. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients cache = ./cache/cord-273050-reez33md.txt txt = ./txt/cord-273050-reez33md.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-275643-lbikoyo3 author = Beidas, Meshal title = Effect of Human Coronavirus OC43 Structural and Accessory Proteins on the Transcriptional Activation of Antiviral Response Elements date = 2018-07-24 pages = extension = .txt mime = text/plain words = 3419 sentences = 192 flesch = 53 summary = The expression of antiviral genes involved in the type I IFN and NF-κB signaling pathways was also downregulated in the presence of HCoV-OC43 structural or accessory proteins. CONCLUSION: Both structural and accessory HCoV-OC43 proteins are able to inhibit antiviral response elements in HEK-293 cells, and to block the activation of different antiviral signaling pathways. Following SeV challenge of HEK-293 cells, the expression of genes involved in the type I IFN and NF-κB signaling pathways was downregulated in the presence of HCoV-OC43 structural or accessory proteins (Fig. 4) . Similar to influenza A NS1 protein, HCoV-OC43 structural (M and N) and accessory (ns2a and ns5a) proteins were able to inhibit the transcriptional activity of antiviral response elements, ISRE, IFN-β promoter, and NF-κB-RE, and to downregulate the expression of several genes involved in the activation of an antiviral response. cache = ./cache/cord-275643-lbikoyo3.txt txt = ./txt/cord-275643-lbikoyo3.txt === reduce.pl bib === id = cord-272117-erzpz3c0 author = Downey, Jeffrey title = Dissecting host cell death programs in the pathogenesis of influenza date = 2018-04-18 pages = extension = .txt mime = text/plain words = 9230 sentences = 440 flesch = 33 summary = Experimentally, apoptosis of IAV-infected epithelial cells was shown to be dependent upon viral replication, as an inactivated virus failed to induce apoptosis in mice [46] and human cells [47] . PKR can directly sense dsRNA generated during viral replication to induce Fas expression and FADD-dependent apoptosis [52] , as well as inhibit host and viral protein translation through the phosphorylation of eIF2a [53] in IAV-infected cells [54] . Additionally, pandemic and highly virulent strains of the virus, including HPAI and the 1918 H1N1 strain, are known to completely exhaust the replicative niche of epithelial cells of the lung over the course of infection as a by-product of overly exuberant replication and failure of immune response to control viral propagation. Collectively, these findings suggest that in contrast to the biphasic role of epithelial cell apoptosis in preventing or promoting pathogenesis, highly virulent IAV rapidly infects and induces early death in pulmonary M4 to suppress antiviral responses. cache = ./cache/cord-272117-erzpz3c0.txt txt = ./txt/cord-272117-erzpz3c0.txt === reduce.pl bib === === reduce.pl bib === id = cord-009567-osstpum6 author = nan title = Abstracts Oral date = 2008-04-23 pages = extension = .txt mime = text/plain words = 131214 sentences = 7728 flesch = 53 summary = Introduction: Previously, it has been demonstrated that FOXP3, a gene required for the development and function of regulatory T cells, was highly expressed in the graft during cardiac rejection, suggesting infiltration of regulatory T cells in the transplanted organ during an allogeneic response. Efficacy and safety parameters assessed at follow-up included: acute rejection; patient and graft survival; renal function, vital signs, basic lab results and immunosuppressive regimen for the patients 10 years after completion of the original study. We analyzed, for the first time, the expression of TLR4 in PBMC from kidney recipients with contrasted situations: operational tolerance and chronic immune-mediated rejection (Banff 2005), compared to patients with normal histology and stable graft function, non transplant patients with renal failure and healthy volunteers. cache = ./cache/cord-009567-osstpum6.txt txt = ./txt/cord-009567-osstpum6.txt === reduce.pl bib === id = cord-273144-er6irjw3 author = Powell, Fiona title = Development of reagents to study the turkey's immune response: Cloning and characterisation of two turkey cytokines, interleukin (IL)-10 and IL-13 date = 2012-06-15 pages = extension = .txt mime = text/plain words = 3956 sentences = 246 flesch = 58 summary = The availability of genome sequences for other avian species, including the zebrafinch (Warren et al., 2010) , the turkey (Dalloul et al., 2010) and the duck (http://pre.ensembl.org/Anas platyrhyncos/Info/), should allow identification and subsequent characterisation of their immune gene repertoires. Real-time qRT-PCR was used to determine IFN-␥ mRNA expression levels in PHA-stimulated splenocytes (from chicken and turkey) treated with recombinant chicken or turkey IL-10 or mock-transfected COS cell supernatant at various dilutions. Similarly, there was inhibition of IFN-␥ production from PHA-stimulated turkey splenocytes by recombinant chicken and turkey IL-10, although Expression patterns of (A) IL-10 and (B) IL-13 mRNA, as measured by real-time quantitative RT-PCR, in lymphoid tissues, non-lymphoid tissues and digestive tissues of the turkey. At the protein level (72 h post-stimulation), recombinant chicken and turkey IL-10 inhibited the production of IFN-␥ by both chicken and turkey splenocytes at high concentrations, as measured by ELISA, and this effect titrated out with increasing dilution of recombinant IL-10 ( Fig. 3C and D respectively). cache = ./cache/cord-273144-er6irjw3.txt txt = ./txt/cord-273144-er6irjw3.txt === reduce.pl bib === id = cord-277409-q5wx313k author = Resende, Lucilene Aparecida title = Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge date = 2016-08-24 pages = extension = .txt mime = text/plain words = 7939 sentences = 372 flesch = 46 summary = Additionally, LbSap has been shown to induce a prominent pro-inflammatory immune response characterized by increased levels of both IL-12 and IFN-γ and decreased levels of TGF-β by peripheral blood mononuclear cells (PBMCs), which were associated with parasite control in dogs [26] . Previous studies of dogs using the "LbSapSal" vaccine displayed higher counts of circulating and Leishmania-specific CD8 + T cells in addition to high nitric oxide (NO) production [22] and reduction of splenic parasite load [27] . chagasi-challenge (T 90) demonstrated that "LbSapSal" group showed a significant increase of TNF-α levels (P<0.05) upon VSA-stimulation as compared to "Sal" and "LbSal" groups ( Fig 1A, middle panel) . The results observed at the post-vaccination period (T 3rd ) demonstrated that the "LbSal" group showed a significant reduction in the IL-10 levels (P<0.05) upon VSA-stimulation as compared to the "Sal" group ( Fig 2B, middle panel) . cache = ./cache/cord-277409-q5wx313k.txt txt = ./txt/cord-277409-q5wx313k.txt === reduce.pl bib === === reduce.pl bib === id = cord-278397-u33x4jaw author = Abe, Takayuki title = Negative Regulation of Cytosolic Sensing of DNA date = 2018-10-29 pages = extension = .txt mime = text/plain words = 7194 sentences = 377 flesch = 41 summary = Recent efforts have focused on identifying relevant immune surveillance sensors and components of downstream signaling-Toll-like receptors (TLRs) and their cognate ligands, cytosolic sensing of RNA (primary mediated by the RIG-I/IPS-1 axis), cytosolic sensing of DNA (primary mediated by the cGAS/STING axis), and the inflammasome pathway (primary mediated by NOD-like receptors; NLRs) (Broz and Monack, 2013; Kieser and Kagan, 2017; Kumar et al., 2011a ). It has also been suggested that chronic cGAS/STING activation induced by self DNA may be responsible for induction of aberrant inflammatory diseases like systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and polyarthritis (Barber, 2015; Crowl et al., 2017) . Use of DNA damage induced agents like 7,12-dimethylbenz-α-anthracene (DMBA) has helped shed light on the underlying events initiate the DNA damage-induced immune response via cytosolic DNA sensing pathway and implicates nucleosome leakage in eliciting cGAS/STING-dependent signal activation via recognition of self-DNA (Barber, 2015) . cache = ./cache/cord-278397-u33x4jaw.txt txt = ./txt/cord-278397-u33x4jaw.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-272695-wmzq4lkh author = Ahmed, Ahmed A. title = TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis date = 2020-05-13 pages = extension = .txt mime = text/plain words = 3813 sentences = 210 flesch = 55 summary = This study was undertaken to test the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. The amplified PCR product for TNF-α-308 was detected at 184 base pair as shown in Fig. 1 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls (supplementary file (Table 3 ). The amplified PCR product for IFN-γ + 874 were detected at 263 base pair as shown in Fig. 2 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls. cache = ./cache/cord-272695-wmzq4lkh.txt txt = ./txt/cord-272695-wmzq4lkh.txt === reduce.pl bib === id = cord-276166-b1e0bbrp author = Li, Shi-fang title = Interferon-omega: Current status in clinical applications date = 2017-10-12 pages = extension = .txt mime = text/plain words = 7734 sentences = 365 flesch = 45 summary = Previous studies showed that glycosylated IFN-ω + ribavirin (RBV) had a synergistic effect in terms of its antiviral activity in hepatitis C virus (HCV)-infected patients [43] . [49] showed that interleukin (IL)-6 production was affected considerably in feline immunodeficiency virus (FIV)-infected cats treated with recombinant feline IFN-ω (rFeIFN-ω) by subcutaneous or oral protocols. Because of its antiviral, immunomodulatory, anti-proliferation, and antitumor activities, IFN-ω has been explored as a treatment option for some diseases and viral infections in humans and other animals. Evaluation of viremia, proviral load and cytokine profile in naturally feline immunodeficiency virus infected cats treated with two different protocols of recombinant feline interferon omega Limited efficacy of topical recombinant feline interferon-omega for treatment of cats with acute upper respiratory viral disease Oral recombinant feline interferon-omega as an alternative immune modulation therapy in FIV positive cats: clinical and laboratory evaluation cache = ./cache/cord-276166-b1e0bbrp.txt txt = ./txt/cord-276166-b1e0bbrp.txt === reduce.pl bib === id = cord-279725-d82sj80v author = Ströher, Ute title = Severe Acute Respiratory Syndrome-Related Coronavirus Is Inhibited by Interferon-α date = 2004-04-01 pages = extension = .txt mime = text/plain words = 2235 sentences = 126 flesch = 52 summary = We evaluated the susceptibility of the SARS-related coronavirus (SARS CoV) to ribavirin and interferon (IFN)-α in vitro by use of cytopathic effect, plaque assay, and immunoblot analysis. To support the search for effective antiviral treatments, we evaluated the susceptibility of SARS CoV isolates (detailed studies were performed with the Tor2 isolate [Toronto, Canada]) to ribavirin and interferon (IFN)-a-2b in vitro. Our data indicate that ribavirin does not inhibit the virus at concentrations attainable in human serum but that IFN-a-2b may be useful and deserves further evaluation as a therapeutic agent. To quantify the effect of IFN-a-2b on the replication of the SARS CoV, Vero E6 cells were infected at an MOI of 0.001 and were incubated in the presence IFN-a-2b (0-5000 IU/mL), as described above. Whether combined therapy with IFN-a-2b and ribavirin would inhibit the replication of the SARS CoV in vitro has not yet been evaluated; the combination is more effective than either agent used alone for the treatment of HCV infection in humans. cache = ./cache/cord-279725-d82sj80v.txt txt = ./txt/cord-279725-d82sj80v.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-024651-578c9ut5 author = nan title = 2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date = 2020-05-11 pages = extension = .txt mime = text/plain words = 84560 sentences = 5089 flesch = 47 summary = Abstract/Case Report Text Introduction: Mutations in the gene encoding signal transducer and activator of transcription 3 (STAT3) cause autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES) characterized by recurrent skin and sinopulmonary infections, atopic dermatitis, and elevated serum immunoglobulin E (IgE) levels. Objective: The purpose of this study is to increase awareness and improve diagnosis of primary immune deficiency (PID) in the heterogenous group of patients with autoimmune cytopenia (AIC) by identifying clinical characteristics and laboratory biomarkers that distinguish those with underlying PID, disease activity and guide mechanism-based targeted therapy. 7 Chief, Laboratory of Clinical Immunology and Microbiology/National Institute of Allergy and Infectious Diseases, NIAID/National Institutes of Health, NIH Abstract/Case Report Text We have previously used the artificial thymic organoid (ATO) system, based on the 3D aggregation and culture of a delta-like canonical Notch ligand 4-expressing stromal cell line (MS5-Dll4) with CD34+ cells, to study T cell differentiation from CD34+ cells obtained from patients carrying defects that are intrinsic to hematopoietic cells (RAG1-2, AK2, IL2RG) or that affect thymus development (DiGeorge syndrome). cache = ./cache/cord-024651-578c9ut5.txt txt = ./txt/cord-024651-578c9ut5.txt === reduce.pl bib === id = cord-278577-bx86tq0y author = Mikola, Emilia title = Tonsillar cytokine expression between patients with tonsillar hypertrophy and recurrent tonsillitis date = 2018-05-22 pages = extension = .txt mime = text/plain words = 3131 sentences = 186 flesch = 43 summary = We investigated the differences in virus detection and T cell and interferon gene expression in patients undergoing tonsillectomy due to tonsillar hypertrophy or recurrent tonsillitis. However, data are scarce on the differences in tonsillar virus infections and immune responses between patients with tonsillar hypertrophy or recurrent tonsillitis [6] [7] [8] . Therefore, we studied whether virus detection and T cell and interferon gene expressions differed between the two main indications of surgery, tonsillar hypertrophy or recurrent tonsillitis. The adjustments for immunologic analyses were chosen using backward stepwise multivariable models that initially included clinical factors and virus infections which significantly differed between the groups (age, self-reported pollen allergy, self-smoking, both adenotomy and tonsillectomy performed, respiratory symptoms one month prior to the operation and bioavailable 25(OH)D level). This study shows differences in virus detections and T cell and interferon gene expressions in patients undergoing tonsillectomy due to tonsillar hypertrophy or recurrent tonsillitis. cache = ./cache/cord-278577-bx86tq0y.txt txt = ./txt/cord-278577-bx86tq0y.txt === reduce.pl bib === id = cord-282947-3hgku2e4 author = Wong, Hui Hui title = Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3 date = 2017-12-30 pages = extension = .txt mime = text/plain words = 8714 sentences = 423 flesch = 46 summary = title: Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3 Through the construction of recombinant IBV expressing proteins 8a, 8b and 8ab encoded by SARS-CoV ORF8, we demonstrate that expression of 8b and 8ab enables the corresponding recombinant viruses to partially overcome the inhibitory actions of IFN activation to achieve higher replication efficiencies in cells. Compared to wild type and rIBV8a/b, however, rIBV8b and rIBV8ab were observed to replicate significantly better and express higher levels of N protein in cells stimulated by poly (I:C) (Fig. 2a) . In view of the central role of IRF3 in regulating IFN activation during virus infection, 8b and 8ab with Flag epitope-tagged to their Ntermini were co-expressed with Myc-tagged IRF3 (Fig. 3a) in Cos-7 cells using the vaccinia/T7 expression system (Anderson et al., 1996; Lim and Liu, 2001) for co-immunoprecipitation assays to determine if there is any physical interaction between the proteins. cache = ./cache/cord-282947-3hgku2e4.txt txt = ./txt/cord-282947-3hgku2e4.txt === reduce.pl bib === === reduce.pl bib === id = cord-275795-ee7qyw5h author = Monette, Anne title = T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders date = 2018-10-24 pages = extension = .txt mime = text/plain words = 28265 sentences = 1205 flesch = 38 summary = We focus on immunity generated against both natural infection and vaccination, where a steady shift in conferred vaccination immunogenicity is observed from quantifying activated and proliferating, long-lived effector memory T cell subsets, as the prominent biomarkers of long-term immunity against viruses and their associated disorders causing high morbidity and mortality rates. Since that time, the occurrence of epidemics and outbreaks are now at lower risk, following the introduction of massive vaccination programs able to induce immune system targeting of viruses causing severe disorders affecting distinct geographical locations, and with many epidemiological reports demonstrating long-term efficacy of viral control of non-naïve populations. This approach is being developed to use virus-infected cell-killing antibodies that produce an antiviral environment; these termed antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, which are predicted to link innate and adaptive immune responses, and is becoming possible due to new technologies for rapid isolation and characterization of monoclonal antibodies targeting conserved regions of influenza virus, reviewed in Jegaskanda et al. cache = ./cache/cord-275795-ee7qyw5h.txt txt = ./txt/cord-275795-ee7qyw5h.txt === reduce.pl bib === id = cord-280005-i9fp5rys author = Wang, Mengmei title = Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide -- a Single-Center, Randomized, Controlled Clinical Trial date = 2020-09-21 pages = extension = .txt mime = text/plain words = 3185 sentences = 172 flesch = 49 summary = title: Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide -a Single-Center, Randomized, Controlled Clinical Trial CONCLUSIONS: In COVID-19 patients with prolonged PCR positivity, no benefit in terms of the duration of viral shedding was observed with the combined treatment of leflunomide and IFN α-2a beyond IFN α-2a alone. Based on that background, we conducted a prospective randomized, controlled, open-label trial, to evaluate the efficacy and safety of oral leflunomide to treat hospitalized COVID-19 patients with prolonged post-symptomatic viral shedding. Fifty eligible patients were randomly assigned to a combination treatment group that received leflunomide (50 mg, q12h, three consecutive times, orally; then 20 mg, once a day for 8 days; a total course of 10 days) plus nebulized IFN -2a (3 million IU each time, adding 2 ml of sterilized water, atomization inhalation twice daily for 10 days), or to a control group that received nebulized IFN -2a This was an open-label, prospective randomized, controlled trial, which was conducted at East Campus, Renmin Hospital of Wuhan University. cache = ./cache/cord-280005-i9fp5rys.txt txt = ./txt/cord-280005-i9fp5rys.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-279733-c0w9bw5u author = Lui, Pak-Yin title = Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 date = 2016-04-20 pages = extension = .txt mime = text/plain words = 5238 sentences = 281 flesch = 48 summary = title: Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response. In non-specialized epithelial cells as well as a subset of specialized immune cells that are susceptible to MERS-CoV infection, 16, 18, 27 type I IFN production is an important part of the host innate immune response and is initiated by ubiquitously expressed cytoplasmic viral sensors in the retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) family in response to the detection of viral pathogen-associated molecular patterns such as double-stranded RNA (dsRNA). Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response cache = ./cache/cord-279733-c0w9bw5u.txt txt = ./txt/cord-279733-c0w9bw5u.txt === reduce.pl bib === id = cord-279781-5ldpz9m9 author = Chen, Chi-Yuan title = Baculovirus as a gene delivery vector: Recent understandings of molecular alterations in transduced cells and latest applications date = 2011-04-28 pages = extension = .txt mime = text/plain words = 13111 sentences = 665 flesch = 38 summary = Concurrent with the aforementioned findings, we also discovered that baculovirus transduction of human BMSCs disturbed the expression of 816 genes, most of which were related to 5 signaling pathways: cell adhesion molecules, TLR, Jak-STAT, apoptosis as well as antigen processing and presentation (Chen et al., 2009b) . immunization of chickens with another VSVG-pseudotyped baculovirus expressing HA of H5N1 avian influenza virus (AIV) also evoked significantly higher levels of H5-specific antibody and cellular immunity than those receiving DNA vaccines, and conferred protection against lethal challenge with the homologous virus strain (Wu et al., 2009b) . Transient and stable gene expression in mammalian cells transduced with a recombinant baculovirus vector Baculovirus as a highly efficient gene delivery vector for the expression of hepatitis delta virus antigens in mammalian cells cache = ./cache/cord-279781-5ldpz9m9.txt txt = ./txt/cord-279781-5ldpz9m9.txt === reduce.pl bib === id = cord-285744-jpw8hen9 author = Byeon, Jung Hye title = Comparison of cytokine responses in nasopharyngeal aspirates from children with viral lower respiratory tract infections date = 2009-01-13 pages = extension = .txt mime = text/plain words = 3314 sentences = 179 flesch = 46 summary = Aim: To determine whether nasopharyngeal aspirates (NPAs) cytokine response is different according to the causative viruses in children with lower respiratory tract infections (LRTI). Several studies (1-3) have investigated cytokine profiles in nasopharyngeal aspirates (NPAs) during viral lower respiratory tract infections (LRTI) in children. Previous studies (1, 3) were demonstrated that patients with respiratory syncytial virus (RSV) infection and those with influenza virus infection induce different cytokine profiles. The present study was performed to determine whether clinical responses in children with LRTI would differ according to causative viruses and to examine the differential patterns of IL-4, IL-5 and IFN-γ concentrations in NPA during acute viral lower respiratory infections according to the causative organisms. The present study of viral LRTI children indicated that as seen in NPAs local inflammatory cytokine responses differed according to the causative organisms. cache = ./cache/cord-285744-jpw8hen9.txt txt = ./txt/cord-285744-jpw8hen9.txt === reduce.pl bib === id = cord-278648-hkvurb2k author = Menachery, Vineet D. title = Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis date = 2017-11-15 pages = extension = .txt mime = text/plain words = 5195 sentences = 263 flesch = 47 summary = While the absence of 2′O-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures and in vivo. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Generation of mutants with changes in the NSP16 KDKE active site resulted in IFN-mediated in vitro and in vivo attenuation of both mouse hepatitis virus (MHV) and SARS-CoV (9, 10) . While a more rapid CPE following both WT and dNSP16 mutant MERS-CoV infections precluded an equivalent finding at late time points, the SARS-CoV results suggest that the absence of NSP16 activity eventually initiates host response changes that contribute to attenuation at late time points. cache = ./cache/cord-278648-hkvurb2k.txt txt = ./txt/cord-278648-hkvurb2k.txt === reduce.pl bib === === reduce.pl bib === id = cord-286072-kgpvdb42 author = Sa Ribero, Margarida title = Interplay between SARS-CoV-2 and the type I interferon response date = 2020-07-29 pages = extension = .txt mime = text/plain words = 7026 sentences = 360 flesch = 43 summary = While awaiting the results of the many clinical trials that are evaluating the efficacy of IFN-I alone or in combination with antiviral molecules, we discuss the potential benefits of a well-timed IFN-I treatment and propose strategies to boost pDC-mediated IFN responses during the early stages of viral infection. IFN, interferon; IFNAR, interferon alpha and beta receptor; IκB, inhibitor of nuclear factor κB; IKKε, IκB kinase-ε; IRF, IFN regulatory factor; ISG, IFN-stimulated gene; JAK, Janus kinase; M, membrane; MAVS, mitochondrial antiviral signaling protein; MDA5, melanoma differentiation-associated gene 5; N, nucleocapsid; Nsp, nonstructural protein; ORF, open reading frame; P, phosphate; PLP, papain-like protease; RIG-I, retinoic acid-inducible gene 1; SARS-CoV, severe acute respiratory syndrome coronavirus; STAT, signal transducer and activator of transcription; TANK, TRAF family member associated NF-κB activator; TBK1, TANK-binding kinase 1; TRAF3, tumor necrosis factor receptor-associated factor 3; TYK2, tyrosine kinase 2. cache = ./cache/cord-286072-kgpvdb42.txt txt = ./txt/cord-286072-kgpvdb42.txt === reduce.pl bib === id = cord-279924-09uwhxs9 author = Plaisted, Warren C. title = T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells date = 2014-01-01 pages = extension = .txt mime = text/plain words = 5580 sentences = 280 flesch = 48 summary = In this study, we demonstrate that cultured murine NPCs are infected by the neurotropic JHM strain of mouse hepatitis virus (JHMV), which induces acute encephalomyelitis and chronic demyelination when injected intracranially into immunocompetent mice. We co-cultured virus-specific CTLs at diminishing effectorto-target (E:T) ratios with NPCs pulsed with the immunodominant CD8 peptide specific for JHMV spike (S) glycoprotein spanning amino acids 510-518 (S510-518), and treated with IFN-γ to induce MHC class I expression. To confirm the role of IFN-γ as the major cytokine contributing to suppression of JHMV replication in infected NPC cultures, monoclonal antibody blockade against the IFN-γ receptor was performed on NPCs before and during treatment with virusspecific CD4þ T cell enriched media. Impaired expression of MHC class II following IFN-γ-treatment of infected NPCs may be a mechanism employed to subvert detection by infiltrating virus-specific CD4þ T cells. cache = ./cache/cord-279924-09uwhxs9.txt txt = ./txt/cord-279924-09uwhxs9.txt === reduce.pl bib === id = cord-022888-dnsdg04n author = nan title = Poster Sessions date = 2009-08-19 pages = extension = .txt mime = text/plain words = 188640 sentences = 9313 flesch = 45 summary = Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. cache = ./cache/cord-022888-dnsdg04n.txt txt = ./txt/cord-022888-dnsdg04n.txt === reduce.pl bib === id = cord-288017-f9b3t0ts author = Kabeerdoss, Jayakanthan title = Understanding immunopathological fallout of human coronavirus infections including COVID‐19: Will they cross the path of rheumatologists? date = 2020-08-10 pages = extension = .txt mime = text/plain words = 4281 sentences = 280 flesch = 46 summary = High risks for fatal disease in COVID‐19 include older age, metabolic syndrome, male gender, and individuals who develop delayed type I IFN response. 54 In a macaque model of SARS-CoV infection too, aged macaques had more severe lung pathology, lower expression of type I IFN and higher expression of pro-inflammatory cytokines as compared to younger macaques. 80 to patients with COVID-19 that it is a mild immunomodulatory F I G U R E 2 Hydroxychloroquine (HCQ) inhibits SARS-CoV-2 entry and inhibits virus-induced type I interferon (IFN) signaling and proinflammatory cytokines production. While male gender, older age and people with metabolic syndrome seem to be at a higher risk of contracting more severe SARS-CoV-2 infection, younger females of African and Asian ancestry have higher risk for developing SLE; male gender among lupus patients, however, is an independent risk factor for severe disease. Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice cache = ./cache/cord-288017-f9b3t0ts.txt txt = ./txt/cord-288017-f9b3t0ts.txt === reduce.pl bib === === reduce.pl bib === id = cord-280130-ewqe9edq author = Weber, Friedemann title = Viral suppression of the interferon system date = 2007-01-27 pages = extension = .txt mime = text/plain words = 4298 sentences = 224 flesch = 39 summary = In most nucleated body cells, viral infections activate transcription of the ''classic'' IFN-b gene [1] by a signaling chain which is initiated by the RNA sensors RIG-I and MDA-5, which in turn act trough the adaptor IPS-1 and the kinases TBK-1 and IKK-3 to activate the transcription factor IRF-3 (see reviews by P. Many RNA and DNA viruses therefore express proteins which bind this key molecule to avoid both IFN induction and activation of dsRNA-dependent antiviral enzymes [7, 8] . Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling Double-stranded RNA binding of influenza B virus nonstructural NS1 protein inhibits protein kinase R but is not essential to antagonize production of alpha/beta interferon cache = ./cache/cord-280130-ewqe9edq.txt txt = ./txt/cord-280130-ewqe9edq.txt === reduce.pl bib === id = cord-286328-ap0wfjhq author = Lewis, Toby C. title = Nasal cytokine responses to natural colds in asthmatic children date = 2012-11-26 pages = extension = .txt mime = text/plain words = 4776 sentences = 260 flesch = 46 summary = CONCLUSIONS & CLINICAL RELEVANCE: We conclude that, in children with asthma, naturally-occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs and IFN-responsive genes. To further examine the innate immune response to viral infection in children with asthma, we measured nasal aspirate cytokine levels in 16 asthmatic children before and after upper respiratory tract infections. We also examined the effects of upper respiratory tract infection on mRNA levels of selected markers of viral infection, including IFNs. Finally, we evaluated a new method of virus detection using a single polymerase chain reaction-ligation detection reaction (PCR-LDR) multiplex assay. We performed home measurements of respiratory symptoms and collected nasal secretions (for detection of viral RNA by PCR and host biomarkers by PCR and ELISA) on 3 days during a week when children were healthy (not reporting upper respiratory tract infection or asthma symptoms), and again during a week when they experienced cold or flu-like symptoms. cache = ./cache/cord-286328-ap0wfjhq.txt txt = ./txt/cord-286328-ap0wfjhq.txt === reduce.pl bib === id = cord-283096-qm7h4qui author = Jeon, Young Joo title = ISG15 and immune diseases date = 2010-02-12 pages = extension = .txt mime = text/plain words = 11144 sentences = 606 flesch = 44 summary = Some of them are type I IFN-induced proteins, such as PKR and RIG-I, and some are the key regulators that are involved in IFN signaling, such as JAK1 and STAT1, implicating the role of ISG15 and its conjugates in type I IFN-mediated innate immune responses. Viral infection also strongly induces ISG15 [18, 19] because one of its major host responses is the production of type I IFNs. A number of proteins that are involved in antiviral signaling pathways, including RIG-I, MDA-5, Mx1, PKR, STAT1, and JAK1, have been identified as target proteins for ISGylation. Swiss 3T3 cells expressing constitutively active MKK7-JNK1β fusion protein show increased resistance to apoptosis induced by vesicular stomatitis virus (VSV) infection, suggesting the involvement of JNK signaling pathway in antiviral response. acid seems to elevate the levels of ISG15 and its conjugates by stimulating cells to secrete IFNs. UBE1L is a 112-kDa protein that shows a 45% identity in amino acid sequence to the human ubiquitin-activating E1 enzyme (UBE1) [73] . cache = ./cache/cord-283096-qm7h4qui.txt txt = ./txt/cord-283096-qm7h4qui.txt === reduce.pl bib === === reduce.pl bib === id = cord-297712-yy4g5npi author = Zhu, Xinyu title = Porcine deltacoronavirus nsp5 inhibits interferon-β production through the cleavage of NEMO date = 2016-12-13 pages = extension = .txt mime = text/plain words = 3284 sentences = 190 flesch = 57 summary = Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-β production by targeting the NF-κB essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV. A study published by our lab also demonstrated that nsp5, the 3C-like protease of porcine epidemic diarrhea virus (PEDV), which is classified into the Alphacoronavirus family, antagonizes IFN-β production by cleavage of NEMO . In this study, we reveal that nsp5 of PDCoV antagonizes the type I IFN signaling pathway through the cleavage of NEMO, a critical constituent of the IKK complex, thus representing a newly identified mechanism by which PDCoV evades the innate immune response. In contrast, TBK1induced activation of the IFN-β promoter was not affected by nsp5 (Fig. 3A) , suggesting that PDCoV nsp5 inhibits RIG-I/MDA5 signaling by targeting NEMO or other upstream proteins. cache = ./cache/cord-297712-yy4g5npi.txt txt = ./txt/cord-297712-yy4g5npi.txt === reduce.pl bib === id = cord-285757-fiqx4tll author = Mäkelä, M. J. title = Lack of Induction by Rhinoviruses of Systemic Type I Interferon Production or Enhanced MxA Protein Expression During the Common Cold date = 1999 pages = extension = .txt mime = text/plain words = 1825 sentences = 97 flesch = 50 summary = To study whether MxA protein expression is systemically upregulated during rhinovirus infection, blood specimens were collected from 40 patients with common cold and MxA expression in mononuclear cells analyzed by flow cytometry. In conclusion, expression of MxA in blood lymphocytes and an apparently systemic type I interferon response is not induced during rhinovirus infection or during most other cases of common cold in young adult patients. In the present study, the induction of a systemic IFN response as reflected by the expression of MxA protein in blood lymphocytes of patients with rhinovirus infection was examined. Our data suggests that type I IFN production in serum is not comparable to that seen in most other respiratory viral infections in vivo, since the rhinovirus-positive patients had only low or no expression of the MxA protein and no IFN-a/b was detectable in serum samples. cache = ./cache/cord-285757-fiqx4tll.txt txt = ./txt/cord-285757-fiqx4tll.txt === reduce.pl bib === === reduce.pl bib === id = cord-296441-682uop9z author = Montoya, María title = Expression Dynamics of Innate Immunity in Influenza Virus-Infected Swine date = 2017-04-21 pages = extension = .txt mime = text/plain words = 6328 sentences = 327 flesch = 52 summary = Swine IV infection induced interferon (IFN)-alpha and interleukin-6 responses in bronchoalveolar fluids (BALF) at day 3 post infection, as opposed to the other non-swine-adapted virus strains. Swine IV infection induced interferon (IFN)-alpha and interleukin-6 responses in bronchoalveolar fluids (BALF) at day 3 post infection, as opposed to the other nonswine-adapted virus strains. In order to answer these questions, samples from pigs infected with a Swine (H3N2) and four different non-swine-adapted H3N8 IV strains circulating in different animal species (dogs, horses, wild aquatic birds, and seals) from our previous study (16) were analyzed and innate immune responses in the respiratory tract were thoroughly investigated. In order to check IV replication in the lower respiratory tract of pigs, BALF samples collected from pigs killed at day 3, 6, and 21 were tested for gene M of the influenza A virus using a quantitative real-time PCR procedure (17) . cache = ./cache/cord-296441-682uop9z.txt txt = ./txt/cord-296441-682uop9z.txt === reduce.pl bib === id = cord-287018-g4y5kjju author = Konstantinova, P title = Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA date = 2006-05-18 pages = extension = .txt mime = text/plain words = 7164 sentences = 454 flesch = 56 summary = In order to solve this durability problem, we tested DNA constructs encoding virus-specific long-hairpin RNAs (lhRNAs) for their ability to inhibit HIV-1 production. The lhRNA constructs were compared with in vitro diced double-stranded RNA and a DNA construct encoding an effective nef-specific shRNA for their ability to inhibit HIV-1 production in cells. For this reason, the DNA constructs encoding lhRNAs (a single-hairpin molecule) and long dsRNAs (two complementary molecules that form a duplex) were designed to target tat, rev and nef sequences as indicated in Figure 1 . 21 nef2 dsRNA induced a decrease in luciferase expression, but an even more pronounced level of inhibition was Figure 1 Scheme of the human immunodeficiency virus type 1 (HIV-1) pLAI proviral genome and target sequences used for the design of long-hairpin RNAs (lhRNAs). cache = ./cache/cord-287018-g4y5kjju.txt txt = ./txt/cord-287018-g4y5kjju.txt === reduce.pl bib === id = cord-285148-bch7814v author = Singanayagam, Aran title = Viruses exacerbating chronic pulmonary disease: the role of immune modulation date = 2012-03-15 pages = extension = .txt mime = text/plain words = 7923 sentences = 393 flesch = 35 summary = However in vitro RV infection of epithelial cells from COPD patients resulted in higher virus load and increased inflammatory mediators, but no differences in interferon production compared to cells from control subjects [87] . List of abbreviations ATF: activating transcription factor; BAL: bronchoalveolar lavage; CF: cystic fibrosis; CFTR: cystic fibrosis transmembrane regulator; COPD: chronic obstructive pulmonary disease; ENA-78: epithelial-derived neutrophilactivating peptide 78; ICAM-1: intercellular adhesion molecule; IFN-α: interferon-alpha; IFN-β: interferon-beta; IFN-λ: interferon-lambda; IFN-γ: interferon-gamma; IL: interleukin; IP-10: IFN-γ-induced protein-10; IRF: interferon regulatory factor; ISG: interferon stimulated genes; MDA-5: melanoma differentiation-associated protein-5; NF-κB: nuclear factor-kappa B; NO: nitric oxide; NOS2: nitric oxide synthase 2; PCR: polymerase chain reaction; PEF: peak expiratory flow; PIV: parainfluenza virus; RANTES: regulated on activation: normal T-cell expressed and secreted; RIG-I: retinoic acid inducible gene I; RSV: respiratory syncytial virus; RV: rhinovirus; SLPI: secretory leukoprotease inhibitor; SOCS: suppressor of cytokine signaling family; Th1/2: T helper 1/2; TLR: toll-like receptors; TNF-α: tumor necrosis factor-alpha -1. cache = ./cache/cord-285148-bch7814v.txt txt = ./txt/cord-285148-bch7814v.txt === reduce.pl bib === id = cord-295781-b831y105 author = VanLeuven, James T. title = Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses date = 2017-06-02 pages = extension = .txt mime = text/plain words = 7213 sentences = 363 flesch = 52 summary = title: Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. While these models are invaluable for evaluating pathology and host responses to infection, parallel in vitro studies can be used to identify gene expression and signaling pathway changes that occur in infected cells to mediate pathogenesis. In this study, we compare the gene expression response of murine lung epithelial cells to infection by three respiratory viruses used in murine models: rhinovirus (serotype RV1B) in the family Picornaviridae, mouse hepatitis virus (MHV strain 1) in the family Coronaviridae, and influenza A virus (strain PR8) in the family Orthomyxoviridae. cache = ./cache/cord-295781-b831y105.txt txt = ./txt/cord-295781-b831y105.txt === reduce.pl bib === id = cord-295684-d3p9nbgq author = Lasfar, Ahmed title = Interferon Lambda: A New Sword in Cancer Immunotherapy date = 2011-12-06 pages = extension = .txt mime = text/plain words = 7850 sentences = 390 flesch = 49 summary = Experiments showed that similar to their human counterparts, mIFN-λ2 and mIFN-λ3 signal through the IFN-λ receptor complex, activate ISGF3, and are capable of inducing antiviral protection and MHC class I antigen expression in several cell types. IFN-α immunoregulatory functions include major histocompatibility complex (MHC) class I expression in normal and tumor cells, activation of NK cells, dendritic cells (DCs), and macrophages, resulting in the promotion of adaptive immune responses against tumors and virally infected cells [19, 20] . The secretion of constant amounts of various cytokines by transduced tumor cells at the site of tumor growth could elicit more To investigate the potential antitumoral role of IFNλ, we first evaluated the response of B16 melanoma cells to IFN-λ, by analyzing STAT1 activation and MHC class I antigen expression. cache = ./cache/cord-295684-d3p9nbgq.txt txt = ./txt/cord-295684-d3p9nbgq.txt === reduce.pl bib === id = cord-283505-ousbar6c author = Horman, William S. J. title = The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection date = 2020-09-24 pages = extension = .txt mime = text/plain words = 5896 sentences = 266 flesch = 45 summary = To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. In this study, we aimed to examine the ferret immune response to H7N9 influenza virus infection by analyzing leukocyte population variation associated with disease pathogenesis. While the day 6 ferret which showed worsened disease progression did exhibit the most severe lung pathology, the lack of viral antigen in and around these lesions (Supplementary Figure 1) means they cannot conclusively be classified as being caused by the influenza infection, and thus we are hesitant to classify disease presentation in this ferret as like a high pathogenicity infection based on the histopathology findings regardless of the increase in clinical signs. Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses cache = ./cache/cord-283505-ousbar6c.txt txt = ./txt/cord-283505-ousbar6c.txt === reduce.pl bib === id = cord-292593-apdyaujt author = Coulter-Mackie, Marion title = In vivo and in vitro models of demyelinating diseases XII. Persistence and expression of corona JHM vims functions in RN2-2 Schwannoma cells during latency date = 1985-10-31 pages = extension = .txt mime = text/plain words = 5832 sentences = 299 flesch = 55 summary = Interference with vesicular stomatitis virus (VSV) production by JHMV was tested in persistently or latently infected RN-2 cells using as the controls, uninfected RN2-2 cells. Since upon infection of RN2-2 cultures with JHMV at 39.5"C and maintenance in a state of latency at that temperature for several days, the cells commenced yielding pfu upon shift down to 32.5"C (Lucas et al., 1978) , these data suggest that penetration and eclipse of the virus inoculum must have occurred normally at 39.5"C and restriction most probably developed at a subsequent stage. It is very significant that during incubation at the restrictive temperature for as long as 7 days and beyond, when RN2-2 cells had multiplied through 6-7 generations, the 56K antigen was readily detectable (channel I), implying that during latency, in the absence of infectious virus production, translation into JHMV nucleocapsid protein continued. cache = ./cache/cord-292593-apdyaujt.txt txt = ./txt/cord-292593-apdyaujt.txt === reduce.pl bib === id = cord-287874-wl0wlxh6 author = Wang, Ling title = Quadruple therapy for asymptomatic COVID-19 infection patients date = 2020-05-03 pages = extension = .txt mime = text/plain words = 5530 sentences = 267 flesch = 45 summary = From 31 January 2020 to 10 February 2020, the patient was given quadruple therapy, including lopinavir/ritonavir tablets (400/100 mg every 12 h), arbidol tablets (0.2 g every 8 h), Lianhuaqingwen granules (a Chinese patent medicine, 6 g every 8 h) orally, and recombinant human interferon-α2b injection via aerosol (6.0 × 10 6 IU with 2 ml of sterilized water for injection every 12 h). • Quadruple therapy, which is lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol, is a common regimen for patients with COVID-19 in China. From 31 January 2020 to 10 February 2020, the patient was treated with four drugs, which are oral administration of lopinavir/ritonavir tablets (400/100 mg every 12 h), arbidol tablets (0.2 g every 8 h), and Lianhuaqingwen granules (a Chinese patent medicine, 6 g every 8 h) and atomization inhalation of recombinant human interferon-α2b injection (6.0 × 10 6 IU with 2 ml of sterilized water for injection every 12 h). cache = ./cache/cord-287874-wl0wlxh6.txt txt = ./txt/cord-287874-wl0wlxh6.txt === reduce.pl bib === id = cord-289101-ko1knslk author = Fu, Weihui title = An open-label, randomized trial of the combination of IFN-κ plus TFF2 with standard care in the treatment of patients with moderate COVID-19 date = 2020-09-20 pages = extension = .txt mime = text/plain words = 6194 sentences = 315 flesch = 48 summary = Our previous clinical pilot study indicated that aerosol inhalation of IFN-k plus TFF2 is a safe treatment and is able to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby resulting in an early release from hospitalization without induction of a proinflammatory response [20] . This study demonstrated that the combination inhalation of IFN-k and TFF2 is able to shorten the time of viral RNA negative conversion and CT improvement, and facilitating patients early discharge from the hospital, in the absence of induction of a proinflammatory response and treatment-related adverse events. The primary endpoint was a significantly shorter time (Mean 3¢80 days, 95% CI 2¢07À5¢53) from the start of the study treatment to viral RNA negative conversion for SARS-CoV-2 in all clinical samples, including nasopharyngeal swabs, throat swabs and stool swabs, in experimental group than in control group (7¢40 days, 95% CI 4¢57À10¢23) (p = 0¢031), and difference between means was 3¢60 days (Fig. 2A) . cache = ./cache/cord-289101-ko1knslk.txt txt = ./txt/cord-289101-ko1knslk.txt === reduce.pl bib === === reduce.pl bib === id = cord-290593-vhmi2559 author = Lannes, Nils title = Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses date = 2012-08-30 pages = extension = .txt mime = text/plain words = 4412 sentences = 250 flesch = 49 summary = title: Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. Considering the possible importance of opsonising antibodies and pDC in the protection against FMDV, the main aim of this study was to characterize the relationship between neutralizing and opsonising activities of polyclonal sera from immunized pigs. Plasmacytoid dendritic cell activation by foot-and-mouth disease virus requires immune complexes cache = ./cache/cord-290593-vhmi2559.txt txt = ./txt/cord-290593-vhmi2559.txt === reduce.pl bib === === reduce.pl bib === id = cord-290396-cy4y8vnt author = Kumar, Matam Vijay title = Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells date = 2004-07-01 pages = extension = .txt mime = text/plain words = 5490 sentences = 363 flesch = 61 summary = title: Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells We evaluated the expression and function of TLRs in human retinal pigment epithelial (RPE) cells. The presence of TLRs on RPE cells and the resultant TLR signaling in RPE cells suggest that these molecules may play an important role in innate and adaptive immune responses within the retina. Our data suggest that the binding of poly I:C, an analog of dsRNA, to TLR 3 on human RPE cells resulted in the production of IFN-h and other cytokines, chemokines, and adhesion molecules. Total RNA prepared from confluent monolayers of human RPE cells and from suspension cultures of U937 was used to evaluate the constitutive expression of TLR mRNA. To study the effects of TLR activators, human RPE cells were washed with serum-free media (SFM) and incubated in SFM for 12 h in the presence of poly I:C (100 Ag/ml ), LPS (5 Ag/ml), or IFN-g (100 U/ml). cache = ./cache/cord-290396-cy4y8vnt.txt txt = ./txt/cord-290396-cy4y8vnt.txt === reduce.pl bib === id = cord-296033-5zyoddl7 author = Hu, Xiaoliang title = Transmissible Gastroenteritis Virus Papain-Like Protease 1 Antagonizes Production of Interferon-β through Its Deubiquitinase Activity date = 2017-10-23 pages = extension = .txt mime = text/plain words = 3357 sentences = 201 flesch = 49 summary = Coronaviruses (CoVs), such as human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome CoV (SARS-CoV), murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), encode papain-like (PL) proteases that inhibit Sendai virus(SeV-) induced interferon (IFN-β) production. Furthermore, TGEV PL1 exerted deubiquitinase (DUB) activity which strongly inhibited the retinoic acid-induced gene I(RIG-1-) and stimulator of interferon gene(STING-) dependent IFN expression. In the present study, we found that TGEV PL1 encoded by the replicase gene could suppress the IFN-expression and inhibit the nuclear translocation of interferon regulatory factor 3 (IRF3) and exerted deubiquitinase (DUB) activity which strongly inhibited the retinoic acid-induced gene I-(RIG-1-) and stimulator of interferon gene-(STING-) dependent IFN expression. We observed the inhibition of SeV-induced IFN-promoter activation in the presence of PL1, similar to the antagonistic function of NL63 PLP2 and porcine epidemic diarrhea virus (PEDV) PLP2, clearly indicating that TGEV PL1 could act as an interferon antagonist. cache = ./cache/cord-296033-5zyoddl7.txt txt = ./txt/cord-296033-5zyoddl7.txt === reduce.pl bib === id = cord-292289-amzzdh3t author = Mochizuki, M. title = Inhibitory effects of recombinant feline interferon on the replication of feline enteropathogenic viruses in vitro date = 1994-03-31 pages = extension = .txt mime = text/plain words = 3226 sentences = 158 flesch = 57 summary = Compared with each virus control culture of fcwf-4 cells, yields of rotavirus, feline panleukopenia virus (FPLV), feline calicivirus and feline infectious peritonitis coronavirus were reduced by ranges of 1.3 to ⩽3.1 log10, 0.6 log2, 0.8 to 3.7 log10 and 0.5 to 0.6 log10, respectively, in the cultures continuously treated with 10 to 10000 U of the rFeIFN. Preformed monolayers of fcwf-4, CRFK or MDCK cells in 24-well cell culture plates (Coming, New York) were treated with the rFelFN at 37°C for 24 h before challenge of VSV, FHV, rotavirus, FIPV and FCV. (2) FPLV Growth of the TU 1 strain in both fcwf-4 and CRFK cell cultures was slightly but IFN dose-dependently inhibited when the cells were continuously treated with the rFelFN for 96 h (Table 1) . The results indicate that certain degrees of antiviral effects against rotavirus, FIPV, FCV and FPLV can be generated in the feline cells by treatment with the rFelFN. cache = ./cache/cord-292289-amzzdh3t.txt txt = ./txt/cord-292289-amzzdh3t.txt === reduce.pl bib === id = cord-297776-k38jssr0 author = Volk, Aaron title = Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages date = 2020-05-18 pages = extension = .txt mime = text/plain words = 5843 sentences = 293 flesch = 42 summary = gene expression, we report significant transcriptional upregulation of multiple genes associated with activation of ER sensors IRE1, ATF6, and PERK, such as Edem1, Hspa5 (encoding BiP protein), and Ddit3 (encoding CHOP), in response to virus replication, with the most robust response detected in cells infected with the wild-type or DUBmut virus infection (Fig. 5B, C, and D) . Overall, these differential gene expression analyses in macrophages reveal similar host responses to the wild-type and DUBmut viruses that include activation of UPR pathways and proinflammatory genes, whereas a distinct transcriptional profile during infection with the EndoUmut virus is predominately defined by a focused, robust antiviral response. The results presented here, and from studies of the MERS-CoV dORF3-5 mutant virus (26) Upon infection of a BMDM with EndoUmut, host double-stranded RNA (dsRNA) sensors (including MDA5, PKR, and OAS) are activated, resulting in robust transcription of type I IFN genes and rapid induction of apoptosis, the latter of which precludes the development of a potent inflammatory response. cache = ./cache/cord-297776-k38jssr0.txt txt = ./txt/cord-297776-k38jssr0.txt === reduce.pl bib === id = cord-294125-v2dr4hm0 author = Albert, Manuel title = ISG15, a Small Molecule with Huge Implications: Regulation of Mitochondrial Homeostasis date = 2018-11-13 pages = extension = .txt mime = text/plain words = 8040 sentences = 444 flesch = 33 summary = Finally, based on our recent observations, we discuss the essential functions of mitochondria in the antiviral response and examine the role of ISG15 in the regulation of mitochondrial processes, specifically OXPHOS and mitophagy. Binding to IFNARs leads to the activation of the Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT) signaling pathway and the formation of the interferon-stimulated gene factor 3 (ISGF3) complex, with the subsequent expression of IFN-stimulated genes [3] that establish an antiviral state and play important roles in determining the host innate and adaptive immune responses [4] . In the following sections, we discuss the antiviral mechanisms mediated by ISGylation of both viral and cellular proteins, with a focus on mitochondrial proteins, as we recently showed that ISG15 modulates essential mitochondrial metabolic processes such as respiration and mitophagy in macrophages, with important implications for innate immune responses [29] . cache = ./cache/cord-294125-v2dr4hm0.txt txt = ./txt/cord-294125-v2dr4hm0.txt === reduce.pl bib === id = cord-304330-egvdvvtx author = Damsky, William title = When interferon tiptoes through COVID-19: Pernio-like lesions and their prognostic implications during SARS-CoV-2 infection date = 2020-06-19 pages = extension = .txt mime = text/plain words = 442 sentences = 32 flesch = 56 summary = William Damsky MD, PhD 1,* , Danielle Peterson MD 1 Brett King MD, PhD 1,* 4 5 has suggested that SARS-CoV-2 infection is sometimes characterized by a muted anti-40 viral Type I and III interferon (IFN) response, 6,7 which may explain progression to 41 severe clinical manifestations in some patients; a robust Type I IFN response was 42 associated with rapid viral clearance and bland disease course. Together, these data suggest that COVID toes may be a 46 marker of patients that are able to mount a robust anti-viral immune response to SARS-CoV-2 and prognosticate a milder course of COVID-19. 6,7 Therefore, we hypothesize that pernio-like lesions, which can 81 occur with elevated Type I IFN signaling, are the result of a robust anti-viral response in patients with COVID-19, and, therefore, are associated with a favorable disease course, 83 as observed in these patients. Pernio-like skin lesions associated 101 with COVID-19: a case series of 318 patients from 8 countries cache = ./cache/cord-304330-egvdvvtx.txt txt = ./txt/cord-304330-egvdvvtx.txt === reduce.pl bib === === reduce.pl bib === id = cord-288238-36hiiw91 author = Keshavarz, Mohsen title = Metabolic host response and therapeutic approaches to influenza infection date = 2020-03-05 pages = extension = .txt mime = text/plain words = 8134 sentences = 425 flesch = 32 summary = It is also reported that influenza infection significantly increases ROS production by inducing Nox4, and the proliferation of this virus in lung epithelial cells is dependent on redox-sensitive pathways activated by Nox4-derived ROS [16] . IFN can also exert its function on metabolic changes by producing several mediators including indoleamine-2,3-dioxygenase (IDO) and nitric oxide (NO), both of which appear to have either an inducible or an inhibitory role in viral replication [33] . In addition, increased temperature of cells during infection (which could be the result of virus replication and fever) causes heat stress which in turn can considerably downregulate carnitine palmitoyltransferase II (CPT II) activity and reduce the β-oxidation and ATP levels in fibroblasts of influenza-associated encephalopathy patients and healthy volunteers [110] . Through enhancing the activity of the mTORC1 complex, the influenza virus strengthens several metabolic pathways, including glycolysis, glutaminolysis, pentose phosphate, and fatty acid synthesis, to provide more ATP and structural materials for viral replication. cache = ./cache/cord-288238-36hiiw91.txt txt = ./txt/cord-288238-36hiiw91.txt === reduce.pl bib === id = cord-299549-bjqwwzam author = Zhang, Lei title = Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis date = 2015-01-01 pages = extension = .txt mime = text/plain words = 3644 sentences = 191 flesch = 47 summary = When the viral infection proceeds to the terminal stage, the key factor would be applying a non-specific immune modulation approach to suppress the cytokine storm that causes multiple organ failure, in an attempt to open a time window for the host's immune system to recover. In most patients, Ebola viral burden elevates by time and triggers an extremely strong immune attack-a phenomenon called 'cytokine storm' (Sullivan et al., 2003) , during which monocytes and/or macrophages produce a massive amount of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukins (ILs), and The virus burden, inflammatory response, and specific antibodies are the main contributors to different outcomes: mortality, survival, or symptomless infection (Fig. 2) , suggesting that the appropriate intervention strategy in each stage would accordingly be able to control the Ebola virus. Nonetheless, this phenomenon does give clues to the treatment against Ebola virus disease (EVD)-early activated innate immune responses may prevent the viral infection. cache = ./cache/cord-299549-bjqwwzam.txt txt = ./txt/cord-299549-bjqwwzam.txt === reduce.pl bib === id = cord-288960-v6l6o5va author = Li, Yang title = Regulating STING in health and disease date = 2017-06-07 pages = extension = .txt mime = text/plain words = 12297 sentences = 689 flesch = 41 summary = Possibly via RIG-I -dependent RNA detection which may in turn induce STING [6] Vesicular stomatitis virus Negative strand ssRNA virus Unknown [6] Human immunodeficiency virus Negative strand ssRNA virus dsDNA reverse transcribed from viral RNA induces cGAS-STING pathway [28] Influenza A virus Negative strand ssRNA virus Possibly via membrane fusion or unknown mechanism independent of DNA recognition [29] Mycobacteria tuberculosis Bacteria producing c-di-GMP c-di-GMP [30, 31] Streptococcus pneumoniae Bacteria dsDNA Bacterial dsDNA [32] Streptococcus pyrogenes Bacteria dsDNA Bacterial dsDNA [33] Staphylococcus aureus Bacteria producing c-di-AMP c-di-AMP [34] Listeria monocytogenes Bacteria producing c-di-AMP c-di-AMP [35] Vibrio cholera Bacteria producing 3′-3′ cGAMP 3′-3′ cGAMP [36, 37] Abbreviations: dsDNA double-stranded DNA, ssRNA single-stranded RNA The type I interferon signal adaptor protein STING is responsible for mediating double-stranded DNA sensing responses and the detection of bacterial cyclic dinucleotides c-di-AMP, c-di-GMP, and 3′-3′ cGAMP. cache = ./cache/cord-288960-v6l6o5va.txt txt = ./txt/cord-288960-v6l6o5va.txt === reduce.pl bib === id = cord-299299-ov6bf1ff author = Janowicz, Anna title = Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8 date = 2015-03-11 pages = extension = .txt mime = text/plain words = 7538 sentences = 406 flesch = 54 summary = Replication of BTV8(H) was relatively poor in interferon (IFN)-competent primary ovine endothelial cells compared to replication of BTV8(L), and this phenotype was determined by several viral genomic segments, including Seg4 and Seg9. Here, in order to determine the roles played by specific BTV genomic segments in virus adaptation to tissue culture and attenuation in vivo, we compared genetic and phenotypic differences between BTV8 NET2006 minimally passaged in tissue culture, a derivative of this strain extensively passaged in cell culture, and 34 reassortants between the two viruses. Both viruses replicated very efficiently in IFN-deficient CPT-Tert cells, but BTV8 H reached titers approximately 100-fold higher than its parental virus (Fig. 1A) . The data obtained so far indicate that BTV8 H had accumulated mutations that affected virus replication in IFN-competent cells and resulted in attenuation in vivo both in IFNAR Ϫ/Ϫ mice and in sheep. cache = ./cache/cord-299299-ov6bf1ff.txt txt = ./txt/cord-299299-ov6bf1ff.txt === reduce.pl bib === id = cord-300319-9k8zseao author = Cinatl Jr., J. title = Infection of cultured intestinal epithelial cells with severe acute respiratory syndrome coronavirus date = 2004 pages = extension = .txt mime = text/plain words = 3017 sentences = 159 flesch = 42 summary = To identify a model for the study of intestinal pathogenesis of severe acute respiratory syndrome (SARS) we tested the sensitivity of six human intestinal epithelial cell lines to infection with SARS coronavirus (SARS-CoV). In both cell lines, SARS-CoV infection deregulated expression of cellular genes which may be important for the intestinal pathogenesis of SARS. To investigate whether ACE2 is a functional receptor for SARS-CoV in intestinal epithelial cell cultures, the cells were pre-treated for 60 min at 37°C with goat antibody directed against the human ACE2 ectodomain (R&D Systems; Wiesbaden-Nordenstadt, Germany). SARS-CoV infection of Caco-2 cells up-regulated OAS2 and MXA but not PKR genes. The discrepancy between transcriptional activation of IFN-induced genes and the ability of SARS-CoV to replicate in Caco-2 cells could be explained by the existence of a specific viral mechanism for escaping IFNinduced anti-viral effects common to most viruses [28] . This justifies the use of intestinal cell lines as a model to study the direct effects of SARS-CoV infection on gene expression in permissive human cells. cache = ./cache/cord-300319-9k8zseao.txt txt = ./txt/cord-300319-9k8zseao.txt === reduce.pl bib === === reduce.pl bib === id = cord-015021-pol2qm74 author = nan title = Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date = 1994 pages = extension = .txt mime = text/plain words = 162327 sentences = 9379 flesch = 50 summary = It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events. cache = ./cache/cord-015021-pol2qm74.txt txt = ./txt/cord-015021-pol2qm74.txt === reduce.pl bib === === reduce.pl bib === id = cord-300648-ixiam7qr author = Zhu, Xun title = IFITM3‐containing exosome as a novel mediator for anti‐viral response in dengue virus infection date = 2014-08-30 pages = extension = .txt mime = text/plain words = 8229 sentences = 367 flesch = 47 summary = At 24 h post infection when the infected cells were examined by real-time RT-PCR assay, strikingly, DENV-2 infection was suppressed potently by the IFITM3-containing exosomes in a dose-dependent manner in parental HeLa cells (Fig. 4A ) or in HeLa cells with endogenous IFITM3 knocked down (Fig. 4C) , and the copy number of DENV-2 viral RNA was reduced in the culture supernatant ( Fig. 4B and D), indicating that the observed antiviral effect was mediated by the exosome-transferred IFITM3. To verify that the enhanced antiviral effects caused by IFITM3-exosome transfer was a result of IFITM3 action rather than a stimulated paracrine IFNs response, the concentration of human IFN-α/β in culture supernatant of HeLa cells or HeLa-siIFITM3 cells treated with IFITM3laden exosomes was measured with ELISA by using Sendai virus (SeV; 100 HAU ml −1 ) as a positive stimulus control. cache = ./cache/cord-300648-ixiam7qr.txt txt = ./txt/cord-300648-ixiam7qr.txt === reduce.pl bib === id = cord-303189-ktl4jw8v author = Coccia, Eliana M. title = Early IFN type I response: Learning from microbial evasion strategies date = 2015-03-31 pages = extension = .txt mime = text/plain words = 15202 sentences = 738 flesch = 40 summary = Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. In these cells, the HCV-induced miR-21 has been recently reported to be involved in evasion of IFN-I production and stimulation of HCV replication, upon suppression of MyD88 and IRAK1 expression, that is required for the TLR7-mediated sensing of the virus [100] . Amongst RNA viruses that, as HCV, can establish a persistent infection, HIV-1, a lentivirus from the Retroviridae family, represents a paradigm for its ability to prevent or circumvent the innate immune response mediated by IFN-I. Overall, viruses as HCV and HIV-1 have evolved nifty strategies to dampen the host innate response in cells where a productive infection may take place, while they induce infection-independent mechanisms in non-permissive cells to facilitate the viral life cycle and promote a chronic inflammation. cache = ./cache/cord-303189-ktl4jw8v.txt txt = ./txt/cord-303189-ktl4jw8v.txt === reduce.pl bib === === reduce.pl bib === id = cord-299754-tgexahwd author = van Tol, Sarah title = The TRIMendous Role of TRIMs in Virus–Host Interactions date = 2017-08-22 pages = extension = .txt mime = text/plain words = 18211 sentences = 1015 flesch = 41 summary = Downstream of the initial pattern recognition, TRIMs also influence the recruitment and interaction of adaptor molecules (stimulator of IFN genes (STING), mitochondrial antiviral signaling protein (MAVS), TGF-β-activated kinase 1(TAK1)/MAP3K7-binding protein (TAB) 2, Myeloid differentiation primary response gene 88 (MyD88), TIR-domain-containing adapterinducing interferon-β (TRIF), NF-κB essential modulator (NEMO), nucleosome assembly protein (NAP-1), and tumor necrosis factor (TNF) receptor-associated factors (TRAF) family memberassociated NF-κB activator (TANK)) and enzymes (TRAF3, TRAF6, TAK1, inhibitor of NF-κB (IκB) kinase (IKK) α,β,ε, TANK binding kinase 1 (TBK1)) to signaling complexes in order to activate transcription factors. Downstream of the initial pattern recognition, TRIMs also influence the recruitment and interaction of adaptor molecules (stimulator of IFN genes (STING), mitochondrial antiviral signaling protein (MAVS), TGF-β-activated kinase 1(TAK1)/MAP3K7-binding protein (TAB) 2, Myeloid differentiation primary response gene 88 (MyD88), TIR-domain-containing adapter-inducing interferon-β (TRIF), NF-κB essential modulator (NEMO), nucleosome assembly protein (NAP-1), and tumor necrosis factor (TNF) receptor-associated factors (TRAF) family member-associated NF-κB activator (TANK)) and enzymes (TRAF3, TRAF6, TAK1, inhibitor of NF-κB (IκB) kinase (IKK) α,β,ε, TANK binding kinase 1 (TBK1)) to signaling complexes in order to activate transcription factors. cache = ./cache/cord-299754-tgexahwd.txt txt = ./txt/cord-299754-tgexahwd.txt === reduce.pl bib === === reduce.pl bib === id = cord-297790-tpjxt0w5 author = Mandl, Judith N. title = Going to Bat(s) for Studies of Disease Tolerance date = 2018-09-20 pages = extension = .txt mime = text/plain words = 9486 sentences = 393 flesch = 40 summary = Among them are filoviruses (e.g., Marburg, Ebola), coronaviruses (e.g., SARS, MERS), henipaviruses (e.g., Hendra, Nipah) which share the common features that they are all RNA viruses, and that a dysregulated immune response is an important contributor to the tissue damage and hence pathogenicity that results from infection in humans. It is likely that differences in evolutionary history of pathogen exposure between bats and humans have led to distinct adaptations in anti-viral immune responses and the ability to tolerate certain infections without disease while being susceptible to others. We summarize this work below, but comparisons of observations made across species suggest that although a number of species appear to be capable of avoiding the pathological effects of RNA virus infection, each bat species may have achieved this through distinct pathways, possibly involving changes to both increase pathogen replication control and to mitigate any immunopathology through decreased inflammatory responses and hence increased disease tolerance. cache = ./cache/cord-297790-tpjxt0w5.txt txt = ./txt/cord-297790-tpjxt0w5.txt === reduce.pl bib === id = cord-299733-4mpz5l9e author = Mitchell, William M. title = Discordant Biological and Toxicological Species Responses to TLR3 Activation date = 2014-04-30 pages = extension = .txt mime = text/plain words = 6164 sentences = 343 flesch = 45 summary = The mechanism of this differential response is consistent with a relative down-regulation of the NF-κB inflammatory cytokine induction pathway in the cynomolgus monkey and humans, but not observed systemically in rat. Primary protein sequences for the human (GenBank U88879); monkey species, including Macaca mulatta (Gen-Bank BAG55034.1 and AY864735), Macaca fasicularis ajp.amjpathol.org -The American Journal of Pathology (GenBank BAG55033.1), Papio anubis (XP_003899477), Callithrix jacchus (JAB01765.1), and Saimiri boliviensis (XP_003899477); and rodents, including the house mouse (GenBank AF355152/Mus musculus) and rat (GenBank AB116229/Rattus norvegicus), dog (GenBank XP_ 005630024/Canis lupus familiaris), and rabbit (GenBank ABB76310/Oryctolagus cuniculus) were aligned using Crystal W software version 10.1.2 provided by DNAStar (Madison, WI). The unexpected differential toxicities observed between the rat and a nonhuman primate prompted an examination of inflammatory cytokines (g-IFN, TNF-a, and IL-12p70) associated with infusion of a TLR3 agonist, rintatolimod. cache = ./cache/cord-299733-4mpz5l9e.txt txt = ./txt/cord-299733-4mpz5l9e.txt === reduce.pl bib === === reduce.pl bib === id = cord-299949-kmn53e2z author = Schultz, Kimberly L.W. title = Immune Responses to Viruses in the CNS date = 2016-05-09 pages = extension = .txt mime = text/plain words = 6946 sentences = 349 flesch = 41 summary = For recovery from infection, the immune response in the central nervous system (CNS) must eliminate or control virus replication without destroying nonrenewable, essential cells. For recovery after virus infection of the central nervous system (CNS), the essential, nonrenewable nature of neurons requires a fine-tuned immune response that controls virus replication without damaging neuronal function. Detailed studies of immune responses to neurotropic viruses have included neuronal infections with rabies virus, flaviviruses, and alphaviruses, as well as infection of multiple cell types with natural mouse pathogens such as Theiler's murine encephalomyelitis virus (TMEV), mouse hepatitis virus (MHV), and lymphocytic choriomeningitis virus (LCMV). Resident cells in the nervous system, including neurons, play an active role in the immune response (Schultz et al., 2014; O'Donnell et al., 2012; Chakraborty et al., 2010; Daffis et al., 2008a; Castorena et al., 2008; Daffis et al., 2007; Commonly used in mouse models of viral encephalitis. cache = ./cache/cord-299949-kmn53e2z.txt txt = ./txt/cord-299949-kmn53e2z.txt === reduce.pl bib === id = cord-304457-8g36h1bz author = Idelsis, E.-M. title = Effect and safety of combination of interferon alpha-2b and gamma or interferon alpha-2b for negativization of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial. date = 2020-08-01 pages = extension = .txt mime = text/plain words = 5862 sentences = 330 flesch = 47 summary = Conclusions: In a cohort of 63 hospitalized patients between 19 to 82 years-old with positive SARS-CoV-2, HeberFERON significantly negativized the virus on day 4 of treatment when comparing with IFN-alpha2b. The RT-PCR after treatment with IFNs on day 14 for hospital discharges was negative to SARS-CoV-2 in 100% and 91% of patients of HeberFERON and control cohorts, respectively. These results confirm the validity of early intervention with the treatment of IFNs in patients with COVID-19, whereas demonstrated in the trial, the combination of type I and type II IFNs impacts strongly in the reduction of the risk for a severe disease likely through the efficient implementation of a timely controlled inflammatory antiviral response against the SARS-CoV-2 infection. Evaluation of the Effect and Safety of HeberFERON vs Heberon Alpha in Patients Infected with Corona Virus SARS-CoV-2 (Study ESPERANZA/HOPE): TRIALS cache = ./cache/cord-304457-8g36h1bz.txt txt = ./txt/cord-304457-8g36h1bz.txt === reduce.pl bib === === reduce.pl bib === id = cord-303893-47lxq8pi author = Jalkanen, Juho title = Interferon beta-1a for COVID-19: critical importance of the administration route date = 2020-06-12 pages = extension = .txt mime = text/plain words = 1276 sentences = 70 flesch = 45 summary = Interferon beta-1a for COVID-19: critical importance of the administration route Juho Jalkanen 1 , Maija Hollmén 2 and Sirpa Jalkanen 2* Type I interferons, especially IFN-beta, have been appointed as potential leading therapeutics to tackle severe COVID-19 and are currently being evaluated in REMAP-CAP and the WHO's Solidarity Trial. We wish to highlight the differences of these two treatment methods and also other crucial aspects of IFN-beta treatment for COVID-19 and acute respiratory distress syndrome (ARDS). Nonetheless, the purpose of i.v. administered IFN-beta for the treatment of COVID-19 and ARDS is to maximise bioavailability of the drug at the lung vasculature, as well as other vascular beds. There are a limited number of direct studies on the timing of immunomodulatory treatments such as IFN-beta, but given our basic understanding of human biology and viral defence, we suggest that IFN-beta should be given early to COVID-19 patients. cache = ./cache/cord-303893-47lxq8pi.txt txt = ./txt/cord-303893-47lxq8pi.txt === reduce.pl bib === id = cord-298259-r9rn0yyz author = Omatsu, Tsutomu title = Induction and sequencing of Rousette bat interferon α and β genes date = 2008-07-15 pages = extension = .txt mime = text/plain words = 2981 sentences = 202 flesch = 63 summary = To investigate the function of type I IFNs upon viral infection in bats, the nucleic acid, and amino acid sequences of Egyptian Rousette (Rousettus aegyptiacus) IFN-α and -β were characterized. Stimulation of bat primary kidney cells (BPKCs) and bat lung cell lines, Tb-1 Lu, with polyinosinic–polycytidylic acid (poly(I:C)) or exogenous bat type I IFNs resulted in increased type I IFNs mRNA expression in BPKCs, but not in Tb-1 Lu. Characterization of the bat IFN-α and -β genes allows understanding of the immune responses upon stimulation in different tissues, thus providing practical strategies for control and treatment of clinically important diseases. These results are important especially for the virus infection, and suggest that future molecular studies on virus infection experiment of bats in vitro will require careful consideration of the differences of type I IFN expression patterns in different cell types. These data suggested that Ebola virus might evade the anti-viral activity of IFNs in bat cells. cache = ./cache/cord-298259-r9rn0yyz.txt txt = ./txt/cord-298259-r9rn0yyz.txt === reduce.pl bib === id = cord-299756-m0va36er author = Raaben, Matthijs title = Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo date = 2009-08-03 pages = extension = .txt mime = text/plain words = 4568 sentences = 258 flesch = 54 summary = As the BALB/c and the IFNAR-/129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Furthermore, gene expression profiling of 129SvEv mice lacking the type I IFN receptor, which are not able to control the MHV infection [11] , allowed us to identify type I IFN-independent transcriptional responses. To study the role of type I IFN-independent and -dependent gene expression in the control of MHV infection in vivo in more detail, we next made use of the IFNAR-/-mice [30] . Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. cache = ./cache/cord-299756-m0va36er.txt txt = ./txt/cord-299756-m0va36er.txt === reduce.pl bib === id = cord-307598-p54p7enk author = Schlee, Martin title = Master sensors of pathogenic RNA – RIG-I like receptors date = 2013-07-01 pages = extension = .txt mime = text/plain words = 12853 sentences = 779 flesch = 56 summary = Similar to TLRs, RIG-I and MDA5 induce type I IFN and chemokines (but no IL12) upon activation by viral but also bacterial RNA. Since type I IFN induction by this RNA required RNase L, the authors concluded that RNase L recognizes and processes viral mRNA into a MDA5 activating structure. Before 5 triphosphate was identified as the crucial RNA modification to induce RIG-I activation, Marques and colleagues observed that synthetic blunt ended dsRNA oligonucleotides can stimulate RIG-I ( Fig. 3 ) (Marques et al. (2010b) confirmed the requirement of a base paired 5 -ppp end of dsRNA for RIG-I activation and suggested that some arenaviruses and bunyaviruses use a prime and realign mechanism for genome synthesis, leading to 5 overhangs in order to evade RIG-I recognition (Marq et al. pneumophilae did not induce type I IFN in HEK293 cells, thus excluding RIG-I-mediated recognition of RNA polymerase-III transcripts in the host cell, as previously suggested (Chiu et al. cache = ./cache/cord-307598-p54p7enk.txt txt = ./txt/cord-307598-p54p7enk.txt === reduce.pl bib === id = cord-302953-gr2kk9w4 author = Baxter, Victoria K. title = Interferon-Gamma Modulation of the Local T Cell Response to Alphavirus Encephalomyelitis date = 2020-01-16 pages = extension = .txt mime = text/plain words = 10529 sentences = 487 flesch = 55 summary = In Phase 1, during the first 7 to 8 days post infection (DPI), both infectious virus and viral RNA increase rapidly, followed by clearance of infectious virus that occurs primarily through cooperative effects of anti-SINV antibody and the cytokine interferon-gamma (IFN-γ) [6] [7] [8] [9] . Gbp2 ( Figure 2A ) and Irgm ( Figure 2B ), two genes associated with autophagy [25] , were highly expressed by SINV-infected dAP-7 cells treated with IFN-γ, as were Oasl2 ( Figure 2C ), a member of the 2'-5'oligoadenylate/RNaseL system [26] , and Rsad2 ( Figure 2D ), which encodes viperin, a protein that interferes with assembly and release of many viruses [27] . To determine the effects of IFN-γ signaling on immune cell subsets after SINV infection, cells isolated from the CLNs and brains of WT, Ifng −/− and Ifngr1 −/− mice were examined by flow cytometry. To determine the effects of IFN-γ signaling on immune cell subsets after SINV infection, cells isolated from the CLNs and brains of WT, Ifng −/− and Ifngr1 −/− mice were examined by flow cytometry. cache = ./cache/cord-302953-gr2kk9w4.txt txt = ./txt/cord-302953-gr2kk9w4.txt === reduce.pl bib === id = cord-305315-0qt7eth0 author = Cao, Liyan title = Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-β production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway date = 2015-08-18 pages = extension = .txt mime = text/plain words = 4245 sentences = 277 flesch = 53 summary = title: Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-β production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway In this study, porcine small intestinal epithelial cells (IECs), the target cells of PEDV, were used as the infection model in vitro to identify the possible molecular mechanisms of PEDV-inhibition IFN-β production. CONCLUSION: Taken together, our data demonstrated for the first time that PEDV infection of its target cell line, IECs, inhibited dsRNA-mediated IFN-β production by blocking the activation of IPS-1 in RIG-I-mediated pathway. PEDV failed to induce IFN-β expression and inhibited poly (I:C)-mediated IFN-β production in IECs Type I IFNs (IFN-α/β) are critical to the host antiviral innate immune response. In summary, the findings of the present study suggested that PEDV-infection in IECs inhibits dsRNA-induced IFN-β induction by interfering with IRF-3 activity associated with RIG-I-mediated signaling pathway. cache = ./cache/cord-305315-0qt7eth0.txt txt = ./txt/cord-305315-0qt7eth0.txt === reduce.pl bib === id = cord-302340-pw2xqhwa author = Feeley, Eric M. title = IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry date = 2011-10-27 pages = extension = .txt mime = text/plain words = 9235 sentences = 553 flesch = 52 summary = Therefore, we have hypothesized that IFITM proteins inhibit susceptible virus families (Orthomyxoviridae, Flaviviridae, Rhabdoviridae, Filoviridae, and Coronaviridae) during the envelope-dependent early phase of the infection cycle, which extends from viral binding to cell surface receptors through the creation of the fusion pore between viral and host membranes [14, 19, 20] . B) MDCK cells stably overexpressing IFITM3 (MDCK-IFITM3) or empty vector control cells (MDCK-Vector) were exposed for 2 h to viral pseudoparticles containing a BLAM-Vpr and expressing either the HA and NA envelope proteins of Influenza A virus (WSN/33, H1N1pp) or the VSV-G envelope protein (VSV-Gpp), then loaded with CCF2. Our assays showed that incoming influenza A viruses were retained in the expanded acidic compartments of both the IFITM3 overexpressing cell lines as well as the IFN-c-treated MEFs, and that IFITM3 partially localized to these structures ( Fig. 2-4, S2-4, S6) . cache = ./cache/cord-302340-pw2xqhwa.txt txt = ./txt/cord-302340-pw2xqhwa.txt === reduce.pl bib === id = cord-307813-elom30nx author = Yip, Tsz-Fung title = Advancements in Host-Based Interventions for Influenza Treatment date = 2018-07-10 pages = extension = .txt mime = text/plain words = 15075 sentences = 735 flesch = 38 summary = Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. A recent study using RNAi also demonstrated that cholesterol homeostasis can be regulated via acid phosphatase 2 (ACP2)-mediated Niemann-Pick C2 activity and impaired the membrane fusion of IAV and influenza B virus (IBV) (52) , further suggesting the importance of controlling cholesterol homeostasis in the release of viral genome to cytoplasm. Furthermore, FPR2 antagonists have been described to possess antiviral activity against not only IAV but also IBV infection (111) , promoting the idea that antagonizing FPR2 to suppress Raf/MEK/ERK signaling cascade could potentially be a novel approach for the treatment of a broad spectrum of influenza viruses. cache = ./cache/cord-307813-elom30nx.txt txt = ./txt/cord-307813-elom30nx.txt === reduce.pl bib === id = cord-305263-fgwf6wy3 author = Wang, Ben X. title = The yin and yang of viruses and interferons date = 2012-02-07 pages = extension = .txt mime = text/plain words = 6285 sentences = 294 flesch = 38 summary = IFN therapy therefore has the advantage over DAA treatments in that, in addition to stimulating genes that block viral replication in infected cells, IFNs activate other innate and adaptive immune responses to combat the virus. For example, polymorphisms in host genes encoding proteins associated with regulation of an IFN response such as interferon receptor a-chain (IFNAR1) [10] , the IFN-inducible myxovirus resistance GTPase protein, Mx [11] , the IFN-inducible 2 0 ,5 0 -oligoadenylate synthetase (OAS) [12] and the suppressor of cytokine signaling (SOCS) 3 associated with regulation of an IFN response [13] , are predictive markers linked with the rate of sustained virological response (SVR) to HCV infection following IFN-a treatment. Remarkably, distinct highly pathogenic respiratory viruses, namely influenza viruses and the SARS-CoV, encode nonstructural proteins in their genomes that function as virulence factors that specifically target the host innate IFN response, further emphasizing the importance of IFNs as broad-spectrum antivirals. cache = ./cache/cord-305263-fgwf6wy3.txt txt = ./txt/cord-305263-fgwf6wy3.txt === reduce.pl bib === id = cord-303344-4aeu9n5v author = Honke, Nadine title = Multiple functions of USP18 date = 2016-11-03 pages = extension = .txt mime = text/plain words = 5890 sentences = 382 flesch = 45 summary = Lacking of USP18 leads to an increase signaling of IFN-I, IFN-III, TNF-α and high levels of conjugated ISG15 Interestingly, knockout mice generated on the FVB/N genetic background are more viable and do not exhibit the severe neurological symptoms that occur in mice generated on a C57BL/6 background, which develop brain injury because of necrosis of ependymal cells. 53 In addition to ISG15, USP18 also specifically inhibits K63-linked ubiquitination of NEMO, leading to the negative regulation of NF-κB activation induced by the TAK1-TAB complex. As expected, this upregulation inhibits IFN-I-induced genes in human microvascular endothelial cells; however, whether USP18 plays a role in controlling bacterial infection has not yet been fully clarified. Because DCs express more USP18 than do other types of cells, the lack of a response to the antiviral effect of IFN-I leads to augmented viral replication and a sufficient amount of autoantigen. cache = ./cache/cord-303344-4aeu9n5v.txt txt = ./txt/cord-303344-4aeu9n5v.txt === reduce.pl bib === id = cord-304553-gbwb7fqi author = Christopher, Mary E. title = Broad-Spectrum Drugs Against Viral Agents date = 2008-09-01 pages = extension = .txt mime = text/plain words = 11323 sentences = 550 flesch = 40 summary = Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. Poly (ICLC), a dsRNA, and CpG ODNs, molecular mimics for TLR3 and TLR9, respectively, have been reported to non-specifically stimulate the innate immune system and to provide protection against various bacterial and viral pathogens, including influenza. Mice treated with two doses of poly (ICLC), 48 h apart, up to 12 d prior to viral challenge were completely protected from infection, whereas survival rates decreased to 80, 40 and 0%, when pre-treatment was given 14, 16 or 20 d prior to virus challenge, respectively [32] . CpG ODN treatment of splenocytes from senescence-accelerated SAM-P1 strain of mice increased IFN-γ and administration in vivo generated virus-specific cytotoxic T lymphocyte responses, NK cell activation, virus-specific Ig isotype switch from IgG1 to IgG2a, increased viral clearance and survival following influenza viral challenge. Viral infection and Toll-like receptor agonists induce a differential expression of type I and lambda interferons in human plasmacytoid and monocyte-derived dendritic cells cache = ./cache/cord-304553-gbwb7fqi.txt txt = ./txt/cord-304553-gbwb7fqi.txt === reduce.pl bib === id = cord-306533-lvm11o4r author = Woo, Bean title = Regulatory interplay between deubiquitinating enzymes and cytokines date = 2019-06-08 pages = extension = .txt mime = text/plain words = 7585 sentences = 449 flesch = 49 summary = DUBs interact with some of the key molecules in the IFN signaling pathway, which include, but are not limited to, RIG-I, stimulator of interferon genes (STING), tumor necrosis factor receptor-associated factors (TRAFs), interferon regulatory factor are summarized in Table 1 . A study conducted using human kidney mesangial cells (MC) showed slightly different results: silencing CYLD in MC cells and stimulating them with poly IC increased the toll-like receptor 3 (TLR3)-induced activation of RIG-I and MDA5 [26] ; however, the level of mRNA of RIG-I and MDA5 actually decreased [26] . However, when USP18 -/-MEF cells with either WT USP18 or DUB activity-mutated USP18 were induced with HSV-1, HCMV or cytosolic DNA, Ifnb, Ifna4, Tnf, IL-6 or Cxcl1 genes increased in expression, indicating that the deubiquitinating activity of USP18 is not responsible for this phenomenon [41] . In a study by Malakhova et al., USP18 inhibited IFN-induced gene activation by affecting JAK-STAT signaling pathway in 293 T cells [44] . cache = ./cache/cord-306533-lvm11o4r.txt txt = ./txt/cord-306533-lvm11o4r.txt === reduce.pl bib === id = cord-306424-gf0bglm0 author = Scutigliani, Enzo Maxim title = Interaction of the innate immune system with positive-strand RNA virus replication organelles date = 2017-06-27 pages = extension = .txt mime = text/plain words = 8320 sentences = 382 flesch = 36 summary = Thus, these data indicate that MAMs are critical locations for antiviral signaling and have an important role in expression of type I and III IFNs. Moreover, increasing evidence suggests that at least some +RNA viruses in fact occupy or hijack MAM-membranes during infection, as MAMs of HCV-infected cells were found to contain proteins involved in virus assembly and fully assembled virions [111] . At last, based on recent studies that demonstrated how IFN-g inducible GTPases are capable of disrupting PVs, we discussed the possibility of a general function of IFN-inducible GTPases in the targeting of viral ROs. In summary, upon infection, +RNA viruses hamper IFN and ISG induction at multiple levels to decelerate antiviral innate immune signaling. Antiviral innate immune response interferes with the formation of replication-associated membrane structures induced by a +RNA virus cache = ./cache/cord-306424-gf0bglm0.txt txt = ./txt/cord-306424-gf0bglm0.txt === reduce.pl bib === id = cord-308298-5ntdb8yf author = Mair, Kerstin H title = Porcine CD8α(dim/-)NKp46(high) NK cells are in a highly activated state date = 2013-03-01 pages = extension = .txt mime = text/plain words = 7630 sentences = 429 flesch = 56 summary = Functional analyses revealed that splenic NKp46(high) NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Splenic NKp46 high NK cells showed a significantly reduced level of CD8α expression compared to the other splenic NK-cell subsets in all animals analysed Sequences of primers (5'-3') for target genes as well as primer positions on (+) strand, length of specific product in base pairs (bp) and product melting temperature in°C are indicated. Splenic NKp46 high NK cells showed an overall higher expression of this receptor compared to NKp46and NKp46 + NK-cell subsets from both spleen and blood. Splenic NKp46 high NK cells showed highly elevated expression of this activating receptor compared to the other two NKp46-defined subsets in spleen as well as in blood in all animals analysed, which could be demonstrated on protein as well as on mRNA level. cache = ./cache/cord-308298-5ntdb8yf.txt txt = ./txt/cord-308298-5ntdb8yf.txt === reduce.pl bib === id = cord-309381-cb80ntxs author = Nogales, Aitor title = Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans date = 2019-09-30 pages = extension = .txt mime = text/plain words = 10222 sentences = 590 flesch = 45 summary = IAV RNAs are mainly recognized by the endosomal, membrane-associated PRR Toll-like receptors (TLRs) 3 (double-stranded RNAs, dsRNAs) or 7/8 (ssRNAs), respectively [50, 51] , by the cytoplasmic PRR retinoic acid-inducible gene I (RIG-I), which detects dsRNA and 5 -triphosphates of the negative ssRNA viral genome [50, 52] , generated during replication of multiple viruses, by the NOD-like receptor family member NOD-, LRR-and pyrin domain-containing 3 (NLRP3), which recognizes various stimuli (see below) [53] and by the absent in melanoma 2 (AIM2) protein, recognizing not well-characterized influenza stimuli [54] . Another important SNP (rs34481144) associated with risk of severe influenza in humans from the United States (US) infected with seasonal IAVs is located in the 5 -UTR of the IFITM3 gene [123, 124] . cache = ./cache/cord-309381-cb80ntxs.txt txt = ./txt/cord-309381-cb80ntxs.txt === reduce.pl bib === id = cord-305959-x061q8t7 author = Davoudi-Monfared, Effat title = A Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of Severe COVID-19 date = 2020-08-20 pages = extension = .txt mime = text/plain words = 4733 sentences = 280 flesch = 50 summary = As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively, P = 0.95). The vital signs at the time of hospital admission were not statistically different, except respiratory rate was significantly higher in the IFN group (22 versus 20, respectively, P ϭ 0.009). As a primary outcome, the time to clinical response was not significantly different between the IFN and control groups (9.7 Ϯ 5.8 versus 8.3 Ϯ 4.9 days, respectively, P ϭ 0.95), which is shown in the Kaplan-Meier plot (Fig. 2) . On day 0, there was no significant difference between the groups in terms of the components Interferon ␤-1a in Treatment of Severe COVID19 Antimicrobial Agents and Chemotherapy of this scale. The present study was the first randomized, open-label, controlled trial that assessed the efficacy and safety of IFN ␤-1a in the treatment of patients diagnosed with severe COVID-19. cache = ./cache/cord-305959-x061q8t7.txt txt = ./txt/cord-305959-x061q8t7.txt === reduce.pl bib === id = cord-311718-z64g8fce author = Chu, Yeonjeong title = Design, synthesis, and biological evaluation of N-arylpiperazine derivatives as interferon inducers date = 2020-10-16 pages = extension = .txt mime = text/plain words = 1967 sentences = 115 flesch = 43 summary = Type I Interferon (IFN) signaling plays an important role in the immune defense system against virus infection and in the innate immune response, thus IFNs are widely used as anti-viral agents and treatment for immune disorder or cancer. We designed and synthesized a series of arylpiperazine derivatives as interferon inducers  We tested different linker system and carbonyl moiety resulted in increase of potency  5i exhibited the activity of interferon inducer with EC 50 of 13.1 μM and no cytotoxicity  5i initiated immune responses by mediating type I IFN signaling Based on these important characteristics of the ARP skeleton, we designed and synthesized a series of 2,3-dichloro ARP derivatives by further N-modification on piperazine part with different linker moiety such as thiourea, urea, and carbonyl functional group in order to assess structure-activity relationship (SAR; Figure 1b All the synthesized compounds were evaluated using ISRE reporter assay on THP-1 human monocyte cells for monitoring immune response. cache = ./cache/cord-311718-z64g8fce.txt txt = ./txt/cord-311718-z64g8fce.txt === reduce.pl bib === id = cord-312955-gs65c3fy author = Schreiber, Gideon title = The Role of Type I Interferons in the Pathogenesis and Treatment of COVID-19 date = 2020-09-30 pages = extension = .txt mime = text/plain words = 8418 sentences = 467 flesch = 48 summary = Although SARS-CoV-2 inhibits the production of IFNβ and thus obstructs the innate immune response to this virus, it is sensitive to the antiviral activity of externally administrated IFN-Is. In this review I discuss the diverse modes of biological actions of IFN-Is and how these are related to biophysical parameters of IFN-I–receptor interaction and cell-type specificity in light of the large variety of binding affinities of the different IFN-I subtypes towards the common interferon receptor. Thereby, it inhibits the nuclear transport of phosphorylated STAT1, rendering cells refractory to IFN-Is. Another example of viral mechanisms that evolved to eliminate IFN-I functions in inducing innate immunity is given by the SARS corona virus, where both the production of IFNb and the IFN-I induced signaling are attenuated. This gene was found to preferentially cleave the ubiquitin-like modifier interferon-stimulated gene 15 (ISG15), FIGURE 4 | SARS-CoV-2 has multiple effects on the immune system, including inhibition of IFNb production, which results in ISGs not to be produced, CD4+ and CD8+ exhaustion and increased levels of pro-inflammatory proteins (TNFa, IL6, NF-kB). cache = ./cache/cord-312955-gs65c3fy.txt txt = ./txt/cord-312955-gs65c3fy.txt === reduce.pl bib === id = cord-309428-qkjjxr6p author = Li, Liwei title = Host miR-26a suppresses replication of porcine reproductive and respiratory syndrome virus by upregulating type I interferons date = 2015-01-02 pages = extension = .txt mime = text/plain words = 5084 sentences = 324 flesch = 53 summary = MicroRNAs (miRNAs) play important roles in viral infections, especially by modulating the expression of cellular factors essential to viral replication or the host innate immune response to infection. To identify host miRNAs important to controlling porcine reproductive and respiratory syndrome virus (PRRSV) infection, we screened 15 miRNAs that were previously implicated in innate immunity or antiviral functions. Luciferase reporters showed that miR-26a does not target the PRRSV genome directly but instead affects the expression of type I interferon and the IFN-stimulated genes MX1 and ISG15 during PRRSV infection. We found that miR-26a does not target the PRRSV genome directly, but rather affects the expression of type I interferon and the IFN-stimulated genes MX1 and ISG15 during PRRSV infection. Indirect immunofluorescence assays (IFA) were performed as described previously (Tian et al., 2011) for the detection of nucleocapsid (N) protein in PRRSV vJX143 infected MARC-145 cells or PAMs pre-transfected with miR-26 family or mutant mimics. cache = ./cache/cord-309428-qkjjxr6p.txt txt = ./txt/cord-309428-qkjjxr6p.txt === reduce.pl bib === === reduce.pl bib === id = cord-310469-v4p01rze author = Livonesi, Márcia Cristina title = In vitro and in vivo studies of the Interferon-alpha action on distinct Orthobunyavirus date = 2007-02-28 pages = extension = .txt mime = text/plain words = 4271 sentences = 244 flesch = 60 summary = Thus, in an effort to characterize antiviral agents that could attenuate infections caused by OROV, CARV, GMAV, GROV and TCMV, we tested the in vitro and in vivo actions of IFN-␣ on these viruses. However, treatment of CARV-, GMAV-or TCMV-infected mice with IFN-␣A did not result in an increase in survival or prolongation of the mean time to death and did not prevent virus replication in the brain of animals (Table 2 and Fig. 3, respectively) . Treatment with IFN-␣A initiated 24 h after mice infection by GROV was unable to inhibit either the death of animals or the viral replication in the brain (Table 3 and Fig. 5 , respectively). In vitro and in vivo results showed that IFN-␣ was able to prevent viral replication in a limited manner, exerting antiviral effect only when administrated early and in high doses, suggesting that OROV, CARV, GMAV, GROV and TCMV present some escape mechanism from antiviral actions of the IFN-␣. cache = ./cache/cord-310469-v4p01rze.txt txt = ./txt/cord-310469-v4p01rze.txt === reduce.pl bib === id = cord-309619-glb2y82u author = Domingo, Pere title = The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19) date = 2020-07-29 pages = extension = .txt mime = text/plain words = 9353 sentences = 508 flesch = 40 summary = Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1–7)/Mas1R axis. SARS-CoV induces the signal transducer and activator of transcription 1 TACE TNF-a converting enzyme TBK1 TANK-binding kinase 1 TLR toll-like receptor TMPRSS2 type II transmembrane serine protease TNF-a tumor necrosis alpha TRAF3 TNF receptor-associated factor 3 XCR1 XCL1 (Chemokine [C motif] ligand 1) and XCL3 (Chemokine [C motif] ligand 3) receptor production of double-membrane vesicles that lack PRRs and can then replicate in these vesicles [18] . COVID-19 patients have high serum levels of inflammatory cytokines, including interleukin (IL)-2, IL-7, IL-10, granulocyte-colony stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage SARS-CoV-2 infects primarily type II pneumocytes through binding to the ACE2 receptor. ACE2 = Angiotensin-converting enzyme 2; SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2; Ang II = Angiotensin II; ROS = Reactive oxygen species; AT1R = Angiotensin 1 receptor; ADAM17 = A disintegrin and metalloproteinase domain 17; TNF-a = Tumor necrosis factor alpha; TMPRSS2 = transmembrane protease serine 2. cache = ./cache/cord-309619-glb2y82u.txt txt = ./txt/cord-309619-glb2y82u.txt === reduce.pl bib === id = cord-310444-02dsqbeg author = Mahlakoiv, T. title = P136 Combined action of type I and type III IFN restricts initial replication of SARS-coronavirus in the lung but fails to inhibit systemic virus spread date = 2012-09-30 pages = extension = .txt mime = text/plain words = 2273 sentences = 127 flesch = 47 summary = Conclusion Our data suggest that the failure of STAT1-deficient mice to efficiently control initial SARS-CoV replication in the lung is due to impaired type I and type III IFN signaling, whereas the failure to control subsequent systemic viral spread is due to unrelated defects in STAT1-deficient mice. The type III interferons are especially important in pulmonary infection, produced in response to viral infection and bacterial PAMPs. IFN-k is activated by and induces NF-jB signaling and promotes expression of Th1 cytokines. Consistent with the expected participation of IFN-k in NF-jB signaling, we measured decreased expression of KC, TNF and GM-CSF and increased IL-10 in the IL-28RÀ/ -BAL (P < 0.05), although there were no significant differences in the populations of immune cells (neutrophils, DC, macrophages) recruited to the airways of the wild type or IL-28RÀ/À mice. Ligation of immunoreceptor tyrosine-based activation motif (ITAM)associated receptors in macrophages can initiate potent induction of negative regulators, including anti-inflammatory cytokine IL-10, signaling inhibitors SOCS3, ABIN3, A20 and transcriptional repressor Hes1 [1] . cache = ./cache/cord-310444-02dsqbeg.txt txt = ./txt/cord-310444-02dsqbeg.txt === reduce.pl bib === id = cord-314333-hkyiy1gm author = Nagata, Noriyo title = Mouse-Passaged Severe Acute Respiratory Syndrome-Associated Coronavirus Leads to Lethal Pulmonary Edema and Diffuse Alveolar Damage in Adult but Not Young Mice date = 2008-06-30 pages = extension = .txt mime = text/plain words = 6908 sentences = 334 flesch = 52 summary = title: Mouse-Passaged Severe Acute Respiratory Syndrome-Associated Coronavirus Leads to Lethal Pulmonary Edema and Diffuse Alveolar Damage in Adult but Not Young Mice Adult mice showed early and acute excessive proinflammatory responses (ie, cytokine storm) in the lungs after SARS-CoV infection, which led to severe pulmonary edema and diffuse alveolar damage. Because advanced age is associated with higher mortality in human SARS patients and SARS-CoV replicates better in aged mice, 6 -10,29 we experimentally infected 6-month-old (adult) female BALB/c mice with F-musX-VeroE6 or the Frankfurt 1 isolate. With regard to the cytokine responses of the mice, the lung homogenates of adult mice on day 1 after inoculation had significantly higher levels of monocyterelated chemokines [ie, MCP-1, macrophage inflammatory protein 1 (MIP-1), and IFN-␥-inducible protein 10 (IP-10)] than those from young mice ( Figure 5 ). cache = ./cache/cord-314333-hkyiy1gm.txt txt = ./txt/cord-314333-hkyiy1gm.txt === reduce.pl bib === id = cord-307333-n6jc0jy3 author = Selvaggi, Carla title = Interferon lambda 1–3 expression in infants hospitalized for RSV or HRV associated bronchiolitis date = 2014-01-02 pages = extension = .txt mime = text/plain words = 6120 sentences = 304 flesch = 49 summary = OBJECTIVES: The airway expression of type III interferons (IFNs) was evaluated in infants hospitalized for respiratory syncytial virus (RSV) or rhinovirus (HRV) bronchiolitis. KEYWORDS IFN lambda; IL-28; IL-29; RSV; HRV; MxA; ISG56; Viral load; Bronchiolitis Summary Objectives: The airway expression of type III interferons (IFNs) was evaluated in infants hospitalized for respiratory syncytial virus (RSV) or rhinovirus (HRV) bronchiolitis. Therefore, we evaluated whether there was a difference in the gene expression of IFN lambda 1e3 subtypes between infants with a clinical diagnosis of RSV associated acute bronchiolitis and those with HRV infection. Results demonstrated that in cells collected from nasopharyngeal washings of RSV positive infants there are higher mRNA levels of type III IFNs compared to those observed in infants with Figure 1 Gene expression of IFN lambda 1e3 during RSV or HRV bronchiolitis. cache = ./cache/cord-307333-n6jc0jy3.txt txt = ./txt/cord-307333-n6jc0jy3.txt === reduce.pl bib === id = cord-310861-9kb0b6rq author = Koo, Bonhan title = An isothermal, label-free, and rapid one-step RNA amplification/detection assay for diagnosis of respiratory viral infections date = 2017-04-15 pages = extension = .txt mime = text/plain words = 5584 sentences = 295 flesch = 58 summary = In this study, we report an isothermal and rapid one-step RNA amplification/detection (iROAD) assay to simultaneously amplify and detect the viral RNA in a label-free and real-time manner. Furthermore, we demonstrated the clinical utility of the iROAD assay by detecting respiratory viral RNAs extracted from the 63 nasopharyngeal samples with either IFN-A/B or HCoV-OC43/229E or RSV-A/B. Subsequently, the iROAD assay detected the respiratory viral targets from the clinical sample by measuring the resonance wavelength shift within 15-20 min (Fig. 1) . In case of the iROAD assay with label-free and real-time capabilities, the wavelength shift was sequentially increased based on the concentrations (2.5×10 1 to 10 5 copies/reaction) of IFN-B within 20 min, as compared to the negative control. In the case of the real-time RT-PCR assay, the fluorescent SYBR Green signal was observed in RNA samples diluted up to 2.5×10 2 copies/reaction and showed good linearity (R 2 =0.9795) for different concentrations of the target (Fig. 3C ). cache = ./cache/cord-310861-9kb0b6rq.txt txt = ./txt/cord-310861-9kb0b6rq.txt === reduce.pl bib === id = cord-311823-85wj08gr author = Katze, Michael G. title = Innate immune modulation by RNA viruses: emerging insights from functional genomics date = 2008 pages = extension = .txt mime = text/plain words = 9154 sentences = 392 flesch = 36 summary = In this section, we review recent studies in which genomic approaches have been used to provide new information on how viruses trigger and regulate innate immune pathways, and to evaluate the use of type I IFN-based therapy as a means to enhance the innate immune response to HCV. In RIg-I-deficient cells, influenza virus fails to elicit the expression of IFNβ and of many ISgs, including key antiviral mediators such as IRF3, STAT1 (signal transducer and activator of transcription 1), IFIT1 (IFN-induced protein with tetratricopeptide repeats 1; also known as ISg56) and ISg54 (also known as IFIT2). Although these studies have provided considerable information regarding the genes activated downstream of TlR activation, it will be advantageous to extend genomic analyses in the context of viral infection using cells lacking the expression of specific TlRs. The ability of a virus to establish an infection depends, at least to some extent, on its ability to block the host innate immune response or to modulate the activity of antiviral effector proteins. cache = ./cache/cord-311823-85wj08gr.txt txt = ./txt/cord-311823-85wj08gr.txt === reduce.pl bib === === reduce.pl bib === id = cord-310252-0cdqhrcw author = Seliger, Barbara title = Chapter 7 IFN Inducibility of Major Histocompatibility Antigens in Tumors date = 2008-12-03 pages = extension = .txt mime = text/plain words = 8538 sentences = 422 flesch = 43 summary = Ag, antigen; APC, antigen presenting cells; APM, antigen-processing machinery; BH, bleomycin hydrolase; bp, base pairs; CIITA, class II transactivator protein; CLIP, class II invariant chain peptide; CTL, cytotoxic T lymphocyte; DC, dendritic cell; ER, endoplasmic reticulum; GAS, gammainterferon-activated site; IFN, interferon; IFN-R1, interferon-receptor-1; IL, interleukin; IRF, interferon regulatory factor; ISG, interferon-stimulated genes; ISGF3, IFN-stimulated gene factor 3; ISRE, interferon-stimulated response element; JAK, janus kinase; LPS, lipopolysaccharide; MAPK, mitogenactivated protein kinase; MCA, methylcholanthrene; MHC, major histocompatibility complex; NF, nuclear factor; NK, natural killer; PKC, protein kinase C; RCC, renal cell carcinoma; SCLC, small-cell lung carcinoma; SOCS, suppressor of cytokine signaling; STAT, signal transducer and activator of transcription; TA, tumor antigen; TAP, transporter associated with antigen processing; TCR, T cell receptor; TFBS, transcription factor-binding sites; TNF, tumor necrosis factor; tpn, tapasin; TPPII, tripeptidyl peptidase II; TSA, trichostatin A; TYK, tyrosine kinase; UIRR, upstream interferon response region; USF1, upstream stimulatory factor 1; wt, wild type. cache = ./cache/cord-310252-0cdqhrcw.txt txt = ./txt/cord-310252-0cdqhrcw.txt === reduce.pl bib === === reduce.pl bib === id = cord-319779-n5w1f0rr author = Lee, Sang-Myeong title = Porcine reproductive and respiratory syndrome virus field isolates differ in in vitro interferon phenotypes date = 2004-12-08 pages = extension = .txt mime = text/plain words = 8214 sentences = 447 flesch = 51 summary = North American porcine reproductive and respiratory syndrome virus (PRRSV) field isolates were studied with regard to IFN-α sensitivity and induction in order to understand the role of type I IFN in PRRSV pathogenesis. PRRSV isolates were differentially sensitive to porcine recombinant IFN-α (rIFN-α) and varied in their ability to induce IFN-α in porcine alveolar macrophages (PAM) cultures as measured by a porcine IFN-α specific ELISA on cell culture supernatants. In this study, North American field isolates of PRRSV were evaluated with respect to induction, sensitivity and suppression of an in vitro type I IFN response. UV-inactivated PRRSV stocks were tested to determine whether virus binding to the cells is responsible for enhanced IFN-a production by polyI:C in cells infected with isolate 3 (Fig. 6) . In this study, North American PRRSV field isolates were evaluated with respect to induction, sensitivity and suppression of an in vitro IFN response in PAM cultures. Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) cache = ./cache/cord-319779-n5w1f0rr.txt txt = ./txt/cord-319779-n5w1f0rr.txt === reduce.pl bib === id = cord-317499-mxt7stat author = Saraya, Takeshi title = Epidemiology of virus-induced asthma exacerbations: with special reference to the role of human rhinovirus date = 2014-05-26 pages = extension = .txt mime = text/plain words = 5655 sentences = 300 flesch = 43 summary = Table 1 shows the frequency of HRV infection in various adult respiratory diseases such as exacerbation of asthma (Nicholson et al., 1993; Atmar et al., 1998; Tan et al., 2003) , common cold (Makela et al., 1998; van Gageldonk-Lafeber et al., 2005) , exacerbation of COPD (Seemungal et al., 2001; Rohde et al., 2003; Tan et al., 2003; Beckham et al., 2005; Papi et al., 2006; Hutchinson et al., 2007; Ko et al., 2007; McManus et al., 2008; Kherad et al., 2010; Dimopoulos et al., 2012; Perotin et al., 2013) , community acquired pneumonia (Jennings et al., 2008; Johnstone et al., 2008; Johansson et al., 2010; Lieberman et al., 2010; Fry et al., 2011; Wootton et al., 2011; Luchsinger et al., 2013; Takahashi et al., 2013; Huijskens et al., 2014) , exacerbation of idiopathic pulmonary fibrosis (Wootton et al., 2011) , and asymptomatic infection (Fry et al., 2011) . cache = ./cache/cord-317499-mxt7stat.txt txt = ./txt/cord-317499-mxt7stat.txt === reduce.pl bib === === reduce.pl bib === id = cord-308932-pp8etmwq author = Baker, M. L. title = Antiviral Immune Responses of Bats: A Review date = 2012-08-01 pages = extension = .txt mime = text/plain words = 8600 sentences = 397 flesch = 45 summary = Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Consistent with the results obtained from bats immunized with /X174 or SRBC antigens, vaccination and experimental viral infections have provided evidence for quantitative and qualitative differences in antibody responses in bats compared with other mammals. It is evident they have similar antibody and T-cell receptor genes, cytokines and chemokines, transcription factors, cluster of differentiation (CD) markers and activation pathways found in the immune responses of other mammalian species. cache = ./cache/cord-308932-pp8etmwq.txt txt = ./txt/cord-308932-pp8etmwq.txt === reduce.pl bib === id = cord-317333-unrd76bo author = Danesh, Ali title = Early gene expression events in ferrets in response to SARS coronavirus infection versus direct interferon-alpha2b stimulation date = 2011-01-05 pages = extension = .txt mime = text/plain words = 5467 sentences = 278 flesch = 48 summary = Evaluation of gene expression patterns in PBMCs and lung necropsies of SARS-CoV-infected ferrets led us to the identification of 7 upregulated IRGs that also were upregulated in response to IFN-α2b injection. Since STAT1 was phosphorylated following SARS-CoV infection and IFN-α2b injection, we investigated select IRG expression by qRT-PCR following in vitro stimulation of ferret peripheral whole blood with IFN-α2b. These gene expression and STAT1 phosphorylation findings suggested that robust IFN responses were activated following SARS-CoV infection 2 days post-infection. The comparison of microarray results between the lung tissue of IFN-α2b and SARS-CoV ferrets at day 1 revealed commonalities in the expression patterns of most IRGs. STAT1, MX1, OAS1, OAS2, ISG15, IFI44, IFI44L and EIF2AK2 were among the overlapping genes (Fig. 3B ). Analysis of the IFN signaling canonical pathway showed the upregulation of STAT1, MX1, OAS1, OAS2, ISG15 and IFI44 in lung necropsies of IFN-α2b injected and SARS-CoV infected ferrets (Fig. 4) . cache = ./cache/cord-317333-unrd76bo.txt txt = ./txt/cord-317333-unrd76bo.txt === reduce.pl bib === === reduce.pl bib === id = cord-307914-lgprrwee author = Bartok, Eva title = Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids date = 2020-07-14 pages = extension = .txt mime = text/plain words = 17726 sentences = 1100 flesch = 51 summary = Indeed, the functionalization of CRISPR/Cas systems as a tool for genomic editing have revealed important differences in human and murine NA sensing, including distinct cell subset expression patterns of NA-sensing Toll-Like Receptors (TLRs) or species differences in the structural requirements for the detection of cyclic dinucleotide cGAMP by STING. As a long dsRNA with a 5 0 diphosphate terminus, polyI:C is known to activate the sensing receptors TLR3, MDA5, and RIG-I (Alexopoulou et al., 2001; Gitlin et al., 2006; Kato et al., 2008; Yoneyama et al., 2005) , accessory proteins such including LGP2 and members of the DDX and DHX families (reviewed in Oshiumi et al., 2016) as well as the restriction factors PKR and the OAS family (Farrell et al., 1978; Hovanessian et al., 1977; Zilberstein et al., 1978) . cache = ./cache/cord-307914-lgprrwee.txt txt = ./txt/cord-307914-lgprrwee.txt === reduce.pl bib === id = cord-312386-88uwlmjx author = Kuchipudi, Suresh V. title = The Complex Role of STAT3 in Viral Infections date = 2015-06-25 pages = extension = .txt mime = text/plain words = 4633 sentences = 261 flesch = 39 summary = Signal transducer and activators of transcription-3 (STAT3) regulates diverse biological functions including cell growth, differentiation, and apoptosis. Signal transducers and activators of transcription (STATs) are a family of transcription factors that play crucial roles in regulating a number of diverse biological functions including cell proliferation, differentiation, apoptosis, inflammatory response, immunity, and angiogenesis [1] . The seemingly contradictory roles of STAT3 in viral infections raise a number of interesting questions: "what factors determine the switch between pro-and anti-inflammatory functions of STAT3?," "how are viruses able to exploit STAT3 signalling for their gene replication?," and "does STAT3 either negatively or positively regulate type 1 IFN response depending on the virus type involved?" Further in depth studies to dissect the role of STAT3 in viral infections could provide valuable insights into viral pathogenesis and development of novel antiviral therapies. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins cache = ./cache/cord-312386-88uwlmjx.txt txt = ./txt/cord-312386-88uwlmjx.txt === reduce.pl bib === id = cord-312001-8p7scli8 author = Majzoub, Karim title = The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans date = 2019-08-16 pages = extension = .txt mime = text/plain words = 10056 sentences = 548 flesch = 46 summary = Consequently, animal cells have evolved devoted pathways which (1) sense and recognize pathogen-associated molecular patterns (PAMPs) and, more particularly, virus-associated molecular signatures; (2) initiate signaling cascades stemming from the site of detection, translocating the information to the nucleus; and (3) induce a transcriptional program that confers an antiviral state to the host ( Figure 1 ). While the cytosolic recognition of viral RNA is almost exclusively mediated by RLRs, several proteins have been proposed to play a role in DNA sensing and triggering innate immune responses, such as the DNA-dependent activator of IFN-regulatory factors (DAI), DDX41, RNA polymerase III, IFI16 and DNA-PK [62] [63] [64] [65] [66] [67] . Although the pathway leading to the transcriptional activation of Vago is still poorly understood in insects, these studies established that DExD/H-box helicase containing proteins, like Dicer and RLRs, may represent an evolutionarily conserved set of viral nucleic acid sensors that direct antiviral responses in animals [159] . cache = ./cache/cord-312001-8p7scli8.txt txt = ./txt/cord-312001-8p7scli8.txt === reduce.pl bib === === reduce.pl bib === id = cord-315328-8g40ukml author = Clementi, Nicola title = Interferon-β-1a Inhibition of Severe Acute Respiratory Syndrome–Coronavirus 2 In Vitro When Administered After Virus Infection date = 2020-06-19 pages = extension = .txt mime = text/plain words = 2275 sentences = 115 flesch = 50 summary = In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection. In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection. In the current study, we assessed its anti-SARS-CoV-2 activity in vitro to give a preclinical background to clinical trials evaluating the possible therapeutic role of IFN-β-1a in patients with coronavirus disease 2019 (COVID-19). Vero E6 cells were treated with concentrations ranging from 5000 to 0.01 IU/mL of IFN-β-1a 1 hour after inoculation with SARS-CoV-2 and monitored for cytopathic effect and real-time-PCR quantitative evaluation at 48, 72, and 96 hours after infection. Our in vitro observations shed light for the first time on that antiviral activity of IFN-β-1a against SARS-CoV-2 when administered after the infection of cells, highlighting its possible efficacy in an early therapeutic setting. cache = ./cache/cord-315328-8g40ukml.txt txt = ./txt/cord-315328-8g40ukml.txt === reduce.pl bib === id = cord-312075-asbt0mcj author = Schulz, Katharina S. title = Viral Evasion Strategies in Type I IFN Signaling – A Summary of Recent Developments date = 2016-11-11 pages = extension = .txt mime = text/plain words = 5763 sentences = 388 flesch = 46 summary = Human T-cell lymphotropic virus type I (HTLV-1) protein Tax disrupts innate immune signaling in multiple ways: it binds to the RIP homotypic interaction motif (RHIM) domains of RIP-1 and disrupts the interaction between RIP-1 and RIG-I or MDA-5 and the activation of the type I IFN promoter. Upon stimulation, TBK1 and IKKε are recruited by adaptor proteins to signaling complexes to be activated by phosphorylation on Ser172 and both have been shown to be subjected to K63-linked polyubiquitination [reviewed in Ref. Interestingly, when a recent study tested how the rabies virus P protein of street strains behaves compared to laboratory-adapted strains with regard to the induction of type I IFN, they found that both street strains and laboratory strains inhibit TBK1-mediated signaling, but only the P protein of street strains also interacts with and inhibits IKKε-inducible IRF3dependent IFNβ expression (88) (Figure 1) . Middle east respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 cache = ./cache/cord-312075-asbt0mcj.txt txt = ./txt/cord-312075-asbt0mcj.txt === reduce.pl bib === === reduce.pl bib === id = cord-317573-wp2wr3b5 author = Peng, Hui title = Human memory T cell responses to SARS-CoV E protein date = 2006-06-30 pages = extension = .txt mime = text/plain words = 4124 sentences = 197 flesch = 60 summary = In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-γ and IL-2 following stimulation with a pool of 9 peptides overlapping the entire E protein sequence. To assess memory T cell response specific for E protein after SARS-CoV infection in humans, PBMCs from individuals who had fully recovered from SARS two years after infection were stimulated with a pool of 9 peptides spanning the entire amino acid sequence of the SARS-CoV E protein, or the cells were stimulated with anti-CD3 and anti-CD28 antibodies under the same culture conditions as positive controls. Similarly, the frequency of SARS-CoV E antigen-specific IFN-g-producing cells determined by IFN-g ELISPOT assay in PBMCs from 8 fully recovered SARS individuals was significantly higher than that of the cells from the normal donor controls in response to E peptides (Fig. 1B) . cache = ./cache/cord-317573-wp2wr3b5.txt txt = ./txt/cord-317573-wp2wr3b5.txt === reduce.pl bib === id = cord-318339-j35w1vsw author = Stockman, Lauren J title = SARS: Systematic Review of Treatment Effects date = 2006-09-12 pages = extension = .txt mime = text/plain words = 4388 sentences = 233 flesch = 50 summary = METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. This paper reports on this systematic review designed to summarise available evidence on the effects of ribavirin, lopinavir and ritonavir (LPV/r), corticosteroids, type I IFN, intravenous immunoglobulin (IVIG), or convalescent plasma in relation to (1) SARS-CoV replication inhibition in vitro; (2) mortality or morbidity in SARS patients; and (3) effects on ARDS in adult patients. cache = ./cache/cord-318339-j35w1vsw.txt txt = ./txt/cord-318339-j35w1vsw.txt === reduce.pl bib === id = cord-321992-lk2ao6m8 author = Annamalai, Thavamathi title = Age-dependent variation in innate immune responses to porcine epidemic diarrhea virus infection in suckling versus weaned pigs date = 2015-12-15 pages = extension = .txt mime = text/plain words = 8539 sentences = 472 flesch = 58 summary = In the present study, we investigated the innate immune responses such as cytokine and NK cell activity as well as changes in frequencies of T cells to examine if differences coincide with the higher disease severity of suckling versus weaned pigs. The infected weaned pigs also had significantly higher NK cell frequencies in blood and ileum at PID 5 (P < 0.05) compared to infected suckling pigs ( Fig. 2A and B) . In infected suckling and weaned groups, peak IFN␣, IL-12 and TNF␣ levels coincided with onset of diarrhea and fecal PEDV RNA shedding and peak serum PEDV RNA titers (PIDs 1 and 3, respectively); and (4) Frequencies of CD3+CD4+ T cells were significantly higher in ileum of suckling pigs than in weaned pigs, whereas there was no difference in frequency of CD3+CD8+ T cells. cache = ./cache/cord-321992-lk2ao6m8.txt txt = ./txt/cord-321992-lk2ao6m8.txt === reduce.pl bib === id = cord-313684-61hkogdh author = Samaddar, Arghadip title = Pathophysiology and Potential Therapeutic Candidates for COVID-19: A Poorly Understood Arena date = 2020-09-17 pages = extension = .txt mime = text/plain words = 11700 sentences = 585 flesch = 42 summary = Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the Wuhan City of China in December 2019 and evolved into a global pandemic. These include antivirals (remdesivir, lopinavir/ritonavir, umifenovir, and favipiravir), interferon, antimalarials (chloroquine/hydroxychloroquine), antiparasitic drugs (ivermectin and nitazoxanide), biologics (monoclonal antibodies and interleukin receptor antagonist), cellular therapies (mesenchymal stem cells and natural killer cells), convalescent plasma, and cytokine adsorber. Though several observational studies have claimed many of these agents to be effective based on their in vitro activities and extrapolated evidence from SARS and Middle East respiratory syndrome (MERS) epidemics, the currently available data remains inconclusive because of ill-defined patient selection criteria, small sample size, lack of concurrent controls, and use of intermediary outcomes instead of patient-relevant outcomes. cache = ./cache/cord-313684-61hkogdh.txt txt = ./txt/cord-313684-61hkogdh.txt === reduce.pl bib === id = cord-315730-fzgxuak7 author = Penman, Sophie L. title = Safety perspectives on presently considered drugs for the treatment of COVID‐19 date = 2020-07-17 pages = extension = .txt mime = text/plain words = 12067 sentences = 627 flesch = 42 summary = Owing to their efficacy against viruses (mostly demonstrated in vitro) including influenza, HIV, coronavirus OC43, and SARS-CoV, a large number of clinical trials (>230) have been registered worldwide using chloroquine/hydroxychloroquine alone, or in combination with other drugs (e.g. azithromycin) for the treatment of COVID-19. At the time of writing, the RECOVERY trial (clinical trial identifier NCT04381936) which is the largest randomised control trial so far conducted for the treatment of COVID, has stopped recruiting to the hydroxychloroquine arm (1542 patients compared with 3132 on standard care) because of no beneficial effect either in terms of mortality or hospital stay (P. Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial cache = ./cache/cord-315730-fzgxuak7.txt txt = ./txt/cord-315730-fzgxuak7.txt === reduce.pl bib === id = cord-323713-bc00vths author = Volpi, Stefano title = Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome date = 2019-05-29 pages = extension = .txt mime = text/plain words = 3225 sentences = 192 flesch = 46 summary = RESULTS: We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Stimulator of IFN genes (STING)-associated vasculopathy with onset in infancy (SAVI) is caused by gain of function mutations in TMEM173 [3] , which lead to a constitutive production of high levels of type I IFNs without infectious triggers [3] [4] [5] . Notably, the clinical responses did not correlate with decreased type I IFN signatures, which improved only transiently in P1 during concomitant treatment with high dose steroids and ruxolitinib (Fig. 2b) . P3 (follow-up of 12 months) after ten months on treatment on ruxolitinib presented clinical and radiological relapse of lung disease requiring glucocorticoid therapy (2 mg/kg/day of prednisone) with a prompt response (Fig. 2a) . cache = ./cache/cord-323713-bc00vths.txt txt = ./txt/cord-323713-bc00vths.txt === reduce.pl bib === id = cord-315483-l6dm82pp author = Santhakumar, Diwakar title = Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses date = 2018-05-01 pages = extension = .txt mime = text/plain words = 10776 sentences = 579 flesch = 47 summary = To confirm the sequence of the cDNA and to identify the genomic structure of the identified IFIT gene, the transcript was amplified from RNA extracted from NDV-infected CEFs. Complete sequence analysis of the gene revealed an open reading frame (ORF) of 1440 bps (479 amino acids excluding stop codon) with high sequence identity (48% and 67%) with the human and duck IFIT5 proteins, respectively ( Supplementary Fig. 1B) . The levels of chIFN-β gene induction was proportional to the NDV replication (Fig. 2D) , therefore, it can be inferred that the virus-induced expression of chicken IFIT5 is IFN-dependent and that chIFIT5 is an early-ISG with capacity to modulate initial steps of virus life cycle. To compare anti-viral effects of chIFIT5 (only IFIT gene identified in chickens so far) with its orthologous and homologous human proteins, huIFIT1, huIFIT2, huIFIT3 and huIFIT5 were expressed in chicken cells and antiviral affect was monitored (Fig. 5A ). cache = ./cache/cord-315483-l6dm82pp.txt txt = ./txt/cord-315483-l6dm82pp.txt === reduce.pl bib === id = cord-318364-5bmdzgla author = Sun, Xinjuan title = Cytokine storm intervention in the early stages of COVID-19 pneumonia date = 2020-04-25 pages = extension = .txt mime = text/plain words = 3102 sentences = 158 flesch = 40 summary = In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response. In support of the above observations, a retrospective study of 41 patients with COVID-19 2 showed that most SARS-CoV-2 infected patients present clinically with mild symptoms, while a minority of patients progressively declined from the infection and eventually died of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MOD). Severe pneumonia caused by pathogenic human coronaviruses (HCoV) are often associated with induced hypercytokinemia, also termed cytokine storm, in immunocompetent individuals; uncontrolled overproduction of inflammatory cytokines contributes to acute lung injury and acute respiratory distress syndrome (ARDS). cache = ./cache/cord-318364-5bmdzgla.txt txt = ./txt/cord-318364-5bmdzgla.txt === reduce.pl bib === === reduce.pl bib === id = cord-322683-wkrj6n1d author = Zhang, Pengfei title = Cellular Poly(C) Binding Protein 2 Interacts with porcine epidemic diarrhea virus Papain-Like Protease 1 and Supports Viral Replication date = 2020-07-13 pages = extension = .txt mime = text/plain words = 4063 sentences = 276 flesch = 57 summary = title: Cellular Poly(C) Binding Protein 2 Interacts with porcine epidemic diarrhea virus Papain-Like Protease 1 and Supports Viral Replication Taken together, these data demonstrated that PLP1 negatively regulated the production of type 1 interferon by interacting with PCBP2 and promoted PEDV replication. The PEDV N protein interacts with the TANK-binding kinase, blocking its association with interferon regulatory factor 3 (IRF3) and thus inhibiting IRF3 activation and type I IFN production (Ding et al., 2014; Hu et al., 2018) . PCBP2 expression is induced following viral infection and acts as a negative regulator of mitochondrial antiviral signaling protein (MAVS), triggering its degradation (You et al., 2009) . Although significant progress has been made in understanding PEDV evasion of innate immune responses, the mechanism of interaction between viral and host cell proteins remains unclear. In the present study, we demonstrated that PLP1 interacted with PCBP2 to inhibit IFN-β production and promote PEDV replication. cache = ./cache/cord-322683-wkrj6n1d.txt txt = ./txt/cord-322683-wkrj6n1d.txt === reduce.pl bib === === reduce.pl bib === id = cord-319501-a2x1hvkk author = Wong, Lok-Yin Roy title = A molecular arms race between host innate antiviral response and emerging human coronaviruses date = 2016-01-15 pages = extension = .txt mime = text/plain words = 7759 sentences = 460 flesch = 51 summary = Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. This suggests SARS-CoV N may interfere with RNA recognition by host immune sensors such as RIG-I and MDA5 thus achieving suppressive role in IFN production. Our group demonstrated that MERS-CoV ORF4a interacts with PACT, a cellular dsRNA-binding protein that optimally activates RIG-Iand MDA5-induced type I IFN production, in an RNAdependent manner (Siu et al., 2014c) . Infection with SARS-CoV and MERS-CoV has been accompanied with suppression of innate immune response, most notably with the suppression of type I IFN production and signaling pathways. Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses pact-induced activation of RIG-I and MDA5 in the innate antiviral response cache = ./cache/cord-319501-a2x1hvkk.txt txt = ./txt/cord-319501-a2x1hvkk.txt === reduce.pl bib === id = cord-320663-xypg6evo author = Market, Marisa title = Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies date = 2020-06-23 pages = extension = .txt mime = text/plain words = 14038 sentences = 659 flesch = 42 summary = A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. Natural Killer (NK) cells are a key component of the innate immune system and are critical in the response to many viral infections in humans and animal models (1) (2) (3) . Altogether these studies show that during acute CoV infection, inflammatory monocyte-macrophages and neutrophils accumulate in the lungs and produce cytokines and chemokines that induce the activation and migration of lymphocytes, including NK cells, to the lungs, where they could be one of the main producers of IFN-γ (148). Studies have reported that patients infected with SARS-CoV-2 have lower levels of circulating NK cells and these express a greater level of inhibitory receptors (e.g., NKG2A) while producing less IFN-γ (127, 129, 130) . cache = ./cache/cord-320663-xypg6evo.txt txt = ./txt/cord-320663-xypg6evo.txt === reduce.pl bib === id = cord-315072-b28yikvj author = Giotis, Efstathios S. title = Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) date = 2016-08-05 pages = extension = .txt mime = text/plain words = 5878 sentences = 285 flesch = 48 summary = title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) To generate a chicken ISG database we have compared data from three transcriptomic technology platforms: (i) the classical 3′-biased GeneChip Chicken Genome Array (32K; Affymetrix, High Wycombe, UK), (ii) the Chicken Gene 1.0 Sense Target (ST) whole transcriptome Array (Affymetrix) and (iii) Illumina (Little Chesterford, UK) RNA-seq. One of the most highly-expressed contigs was one which, when analysed by BLAST, proved to represent a homologue of STAT2, which is missing from the current ENSEMBL annotated reference chicken genome In (B) PYURF shows 24-fold suppression by IFN but the sequence surrounding PYURF shows 87-fold induction from the right-hand end of the unannotated, antisense LOC422513 and considerably higher upregulation from the left-hand end (due to its lower uninduced levels), consistent with these representing homologues of IFN-inducible human genes HERC6 and HERC5. Technologies identifying significant IRGs are listed as "1" RNA-seq (using Kal's Z test); "2" Affymetrix 32K GeneChip Chicken Genome Array and "3" Chicken Gene 1.0 ST Array' . cache = ./cache/cord-315072-b28yikvj.txt txt = ./txt/cord-315072-b28yikvj.txt === reduce.pl bib === === reduce.pl bib === id = cord-314505-7qh8dsew author = Stegelmeier, Ashley A. title = Myeloid Cells during Viral Infections and Inflammation date = 2019-02-19 pages = extension = .txt mime = text/plain words = 12519 sentences = 640 flesch = 35 summary = The induction of the IFN response following viral infections fundamentally changes the bone marrow microenvironment ( Figure 1B) , leading to the enhanced differentiation of myeloid cells [24] and emigration of neutrophils and monocytes to the site of infection, which is facilitated by chemokine gradients interacting with their cognate receptors ( Figure 1A ) [25] . TLR stimulation after phagocytosis activates the NF-κB signaling cascade, resulting in the release of inflammatory cytokines such as TNF-α, IL-1, and IL-6 from monocytes [4] to control virus infections by direct antiviral mechanisms and the recruitment of other leukocytes. Taken together, these findings suggest that type I IFN signaling drives a balance of pro-and anti-inflammatory effects on the functions of monocytes and neutrophils in response to viral infections; providing protective immunity while simultaneously limiting immunopathology. Importantly, viruses and virus-mediated tissue damage stimulate both neutrophils and monocytes, triggering a cascade of cytokine/chemokine-mediated innate immune responses. cache = ./cache/cord-314505-7qh8dsew.txt txt = ./txt/cord-314505-7qh8dsew.txt === reduce.pl bib === id = cord-321050-yabt72jf author = Tuttle, Kathryn D. title = JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy date = 2020-04-09 pages = extension = .txt mime = text/plain words = 4121 sentences = 208 flesch = 46 summary = Increasing evidence supports the notion that mortality during infections with SARS-CoV-2, which causes coronavirus disease of 2019 , is driven by the exacerbated immune response to the virus, leading to a cascade of events involving a cytokine storm and acute respiratory distress syndrome (ARDS), often accompanied by myocardial damage and multiple organ failure (5, 6) . Overall, these results have potential far-reaching significance for the treatment of COVID-19, justifying a deeper study of JAK inhibitors as a therapeutic strategy to attenuate the cytokine storm and downstream organ failure in this condition, while also indicating that individuals with DS should be considered a high-risk population during the COVID-19 pandemic. This analysis revealed that Dp16 mice have increased liver pathology even before P(I:C) treatment, as demonstrated by significantly higher levels of cell injury, inflammation, and reactive changes relative to their WT littermates (Figure 4B,C) . cache = ./cache/cord-321050-yabt72jf.txt txt = ./txt/cord-321050-yabt72jf.txt === reduce.pl bib === id = cord-320338-jv76j6wx author = Lee, Kyungjin title = Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion date = 2017-12-15 pages = extension = .txt mime = text/plain words = 5009 sentences = 263 flesch = 41 summary = In this study, we found that the addition of exogenous cytidine, uridine and uridine mono-phosphate (UMP) effectively reversed the antiviral activity of gemcitabine in enterovirus-infected as well as enteroviral replicon-harboring cells, demonstrating gemcitabine's targeting of the salvage pathway. At first, in order to test if the anti-enteroviral activity of gemcitabine is related with the inhibition of pyrimidine biosynthesis, HeLa cells were infected with CVB3 and simultaneously treated with excessive 4 nucleosides (adenosine, guanosine, uridine and cytidine) in the presence of various doses of gemcitabine for 8 hours. HeLa cells were treated with increasing doses of gemcitabine or IFN-α for 24 hours and then total RNAs were prepared for quantitative real-time PCRs. As a result, gemcitabine strongly induced two genes (IFIT1 and DDX58) up to and UMP) (100 μM) of pyrimidine biosynthetic pathway were treated as described in Figure 1A (A) and in Figure 1B (B) . cache = ./cache/cord-320338-jv76j6wx.txt txt = ./txt/cord-320338-jv76j6wx.txt === reduce.pl bib === id = cord-323756-atnrw9ew author = Vabret, Nicolas title = Sensing Microbial RNA in the Cytosol date = 2013-12-25 pages = extension = .txt mime = text/plain words = 6409 sentences = 355 flesch = 45 summary = When Janeway formulated the theory of pattern recognition in 1989, he proposed that host cells could sense microbial infection owing to receptors able to recognize invariant molecular structures defined as pathogen-associated molecular patterns (PAMPs). They share a similar organization with three distinct domains: (i) a C-terminal repressor domain (RD) embedded within the C-terminal domain (CTD); (ii) a central ATPase containing DExD/H-box helicase domain able to bind RNA; and (iii) a N-terminal tandem CARD domain that mediates downstream signaling, and which is present in RIG-I and MDA5 but absent in LGP2. DDX60 has also been shown to enhance the IFN-I response to RNA and DNA stimulation through formation of complexes with Frontiers in Immunology | Molecular Innate Immunity RIG-I, MDA5, and LGP2 but not with MAVS. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses cache = ./cache/cord-323756-atnrw9ew.txt txt = ./txt/cord-323756-atnrw9ew.txt === reduce.pl bib === === reduce.pl bib === id = cord-327685-fymfqvp3 author = Channappanavar, Rudragouda title = Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology date = 2017-05-02 pages = extension = .txt mime = text/plain words = 5834 sentences = 288 flesch = 33 summary = In contrast, highly pathogenic hCoVs such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) predominantly infect lower airways and cause fatal pneumonia. Severe pneumonia caused by pathogenic hCoVs is often associated with rapid virus replication, massive inflammatory cell infiltration and elevated pro-inflammatory cytokine/chemokine responses resulting in acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Although there is no direct evidence for the involvement of pro-inflammatory cytokines and chemokines in lung pathology during SARS and MERS, correlative evidence from patients with severe disease suggests a role for hyper-inflammatory responses in hCoV pathogenesis. Infection of non-human primates (NHPs) with SARS-CoV induced a dysregulated immune response resulting in increased disease severity in aged but not young NHPs, despite similar viral titers in the airways [67] . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice cache = ./cache/cord-327685-fymfqvp3.txt txt = ./txt/cord-327685-fymfqvp3.txt === reduce.pl bib === id = cord-321947-qek9jy2c author = Lee, Su Jeen title = Evaluation of glycoprotein E subunit and live attenuated varicella‐zoster virus vaccines formulated with a single‐strand RNA‐based adjuvant date = 2020-03-13 pages = extension = .txt mime = text/plain words = 5482 sentences = 334 flesch = 57 summary = In VZV-primed mice, we assessed whether this ssRNA adjuvant induces humoral-and cell-mediated immunity in the VZV gE subunit vaccine. However, we used guinea pigs to evaluate the ability of the ssRNA adjuvant to enhance neutralizing antibody production and cell-mediated immune response in VZV LAV. Based on all results, we showed the potential of ssRNA adjuvants to compensate for the limitations of protein-based vaccines with respect to low T-cell activity and short-term responses, as well as to increase the neutralizing antibody in LAV for preventing VZV-induced disease. 41 Here, the ssRNA adjuvant-induced humoral and balanced Th1/Th2 immune responses even though its antibody and cytokine induction levels in the VZV gE protein subunit vaccine were lower than those for AddaVax. Nevertheless, the mode of action of AddaVax has not yet been elucidated. Moreover, the ssRNA derived from CrPV IGR IRES encoding the gE gene, which could express gE in transfected cells, can effectively function as a vaccine adjuvant in a protein-based subunit vaccine by activating humoral and cell-mediated immune responses. cache = ./cache/cord-321947-qek9jy2c.txt txt = ./txt/cord-321947-qek9jy2c.txt === reduce.pl bib === === reduce.pl bib === id = cord-325989-nf6ouaq3 author = Es-Saad, Salwa title = Regulators of innate immunity as novel targets for panviral therapeutics date = 2012-09-24 pages = extension = .txt mime = text/plain words = 3731 sentences = 201 flesch = 34 summary = The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. Better characterization of pathogen-induced immune disorders and newly discovered regulators of innate immunity have now the potential to specifically withdraw prevailing subversion mechanisms and to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies. In the near future, targeting specific regulators of PRR-mediated innate response to withdraw viral subversion mechanisms, and access to novel surrogate measurable effector markers, hold the promise of new panviral therapeutics that will minimize adverse effects associated with type I IFN therapy. cache = ./cache/cord-325989-nf6ouaq3.txt txt = ./txt/cord-325989-nf6ouaq3.txt === reduce.pl bib === === reduce.pl bib === id = cord-325624-6anybxnk author = Ireland, Derek D. C. title = RNase L Mediated Protection from Virus Induced Demyelination date = 2009-10-02 pages = extension = .txt mime = text/plain words = 8082 sentences = 397 flesch = 43 summary = The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. RNase L specifically protected the brain stem from sustained infection and prevented spread of virus to microglia/macrophages located in spinal cord grey matter. The increased pathological changes in both brain stem and spinal cord thus correlated with the high mortality rates of RL 2/2 mice starting at day 9 p.i. The inability to directly link increased axonal damage with enhanced neuronal infection remains puzzling and supports dysregulation of oligodendrocyte function and/or neuroprotective functions of microglia as contributing factors to the severe pathological phenotype and clinical outcome. Numerous functions of RNase L, not directly associated with anti-viral activity, may contribute to the increased susceptibility of RL 2/2 mice to MHV-JHM infection. cache = ./cache/cord-325624-6anybxnk.txt txt = ./txt/cord-325624-6anybxnk.txt === reduce.pl bib === id = cord-330176-1ugzkf22 author = Weeratunga, Prasanna title = RETRACTED ARTICLE: Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components date = 2016-01-05 pages = extension = .txt mime = text/plain words = 7948 sentences = 396 flesch = 53 summary = In vitro, an effective dose of Angelica tenuissima Nakai markedly inhibited the replication of Influenza A virus (PR8), Vesicular stomatitis virus (VSV), Herpes simplex virus (HSV), Coxsackie virus, and Enterovirus (EV-71) on epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. To investigate the antiviral effects in immune cells, we first assessed the replication of divergent GFP-expressing viruses that were treated or untreated with cytotoxic-free (data not shown) Angelica tenuissima Nakai in RAW264.7 cells. These results suggest that the aqueous extract of Angelica tenuissima Nakai can induce the secretion of IFNs and pro-inflammatory cytokines, which can stimulate the cellular antiviral state for inhibition of viral replication. The aqueous extract of Angelica tenuissima Nakai inhibit the diverse viral infection through the induction of Type I IFN signaling and pro-inflammatory cytokines, leading to an antiviral state in epithelial and immune cells. cache = ./cache/cord-330176-1ugzkf22.txt txt = ./txt/cord-330176-1ugzkf22.txt === reduce.pl bib === id = cord-325825-0lyt8gfq author = Griffiths, Samantha J. title = A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date = 2013-08-08 pages = extension = .txt mime = text/plain words = 12504 sentences = 601 flesch = 45 summary = Host factors (HFs) which positively or negatively regulate HSV-1 replication were identified by screening a druggable genome siRNA library (4 siRNAs per gene) targeting 7,237 human genes against a HSV-1 reporter virus expressing the enhanced green fluorescent protein (eGFP; HSV-1 strain C12) in the epithelial Hela cell line, due to their ease of transfection and susceptibility to HSV-1 infection [34] . Combined bioinformatic analyses of protein interaction and siRNA depletion screens found a significant functional enrichment for proteins involved in transcription, and identified multi-protein complexes enriched for pro-viral HFs which strongly inhibited HSV-1 upon depletion, including the RNA-polymerase II, eIF3 and Mediator complexes ( Figure 3a) . Furthermore, qPCR analysis found depletion of Med23 inhibited the induction of IFN-l expression following HSV-1 infection of A549 cells in comparison to cells transfected with the RSCF siRNA control ( Figure 4e ). cache = ./cache/cord-325825-0lyt8gfq.txt txt = ./txt/cord-325825-0lyt8gfq.txt === reduce.pl bib === id = cord-326762-t89jtjmi author = Chen, Weiye title = Establishment of a stable CHO cell line with high level expression of recombinant porcine IFN-β date = 2011-06-30 pages = extension = .txt mime = text/plain words = 4042 sentences = 185 flesch = 50 summary = title: Establishment of a stable CHO cell line with high level expression of recombinant porcine IFN-β Abstract A CHO cell clone (CHO-PoIFN-β) with stable porcine IFN-β expression under control of CMV promoter was selected under G418 pressure. The purpose of this study was to establish highly efficient and stable expression of recombinant porcine IFN-b in CHO-K1 cell line, and further characterize the biological activity of the product. In order to study the antiviral capacity of recombinant PoIFN-b against porcine viruses in vitro, PK15 cells were treated with 10-fold serially diluted PoIFN-b CHO (start from1.1  10 6 IU/ml) for 24 h, and then infected with 1000 TCID 50 of TGEV (Fig. 4A-C) or PRV (Fig. 4F-H) . The CHO-PoIFN-b cell line established in this study expresses the recombinant PoIFN-b that has the same biological function as natural porcine type I IFN. cache = ./cache/cord-326762-t89jtjmi.txt txt = ./txt/cord-326762-t89jtjmi.txt === reduce.pl bib === id = cord-328252-dk54w8z9 author = Kikkert, Marjolein title = Innate Immune Evasion by Human Respiratory RNA Viruses date = 2019-10-14 pages = extension = .txt mime = text/plain words = 11552 sentences = 550 flesch = 43 summary = Whether PA-X also degrades viral dsRNA species to prevent recognition by cytosolic RNA sensors is not entirely clear, but mutant viruses in which this PA-X protein was expressed in significantly lower amounts elicited higher levels of innate immune response; for example, IFN-beta production was much higher in these infections [71] . This indeed suggests that PA-X, besides having a role in the degradation of cellular mRNAs, may also degrade viral RNA to prevent recognition by innate immune sensors and activation of innate immune responses, similar to what was shown for the CoVs. To my knowledge, an endoribonuclease has not been identified in the RSV genome, so this virus may use alternative innate immune evasion strategies, as discussed elsewhere in this review. [91] suggested that RSV specifically targets mRNA encoding surfactant protein A, an innate immune factor with an important role in the epithelial tissue of the lung, which directly binds to virus particles to cause their destruction by host defense mechanisms. cache = ./cache/cord-328252-dk54w8z9.txt txt = ./txt/cord-328252-dk54w8z9.txt === reduce.pl bib === === reduce.pl bib === id = cord-335384-co2fgz26 author = Lobo‐Silva, Diogo title = Interferon‐β regulates the production of IL‐10 by toll‐like receptor‐activated microglia date = 2017-06-15 pages = extension = .txt mime = text/plain words = 7144 sentences = 385 flesch = 50 summary = These differential responses were not dependent on the dose of agonist used to stimulate microglia, as increasing the doses of TLR ligands did not result in enhanced secretion of IL-10, nor of TNF (Supporting Information, Figure 1 ). Considering the cytokine landscape obtained upon TLR3 triggering of microglia (Figure 1 ), if such mechanism was operating, the best candidate molecule would be IFN-b, as it is strongly induced by TLR3 ( Figure 1g ) and it has been described to potentiate IL-10 in studies performed with bone marrow-derived macrophages and dendritic cells (Iyer, Ghaffari, & Cheng, 2010; F. Co-stimulation of microglia with TLR3 enhanced IL-10 production via IFN-b, thus opening a novel mechanism underlying its beneficial role in MS and being a possible tool to locally regulate inflammatory responses. cache = ./cache/cord-335384-co2fgz26.txt txt = ./txt/cord-335384-co2fgz26.txt === reduce.pl bib === id = cord-328804-f7etlk5i author = Olofsson, Peter title = Arthritis suppression by NADPH activation operates through an interferon-β pathway date = 2007-05-09 pages = extension = .txt mime = text/plain words = 7779 sentences = 368 flesch = 48 summary = Hence, global gene-expression profiling on inguinal lymph nodes was performed 10 days after the induction of pristane-induced arthritis (PIA) and phytol administration. To analyze the in vivo effects of the NADPH oxidase activator phytol versus the effects of the arthritis-inducing compound pristane, global gene-expression profiling was performed. By studying gene-expression profiles and performing pathway analysis, we have identified the importance of an IFN-β-dependent pathway as one molecular mechanism for the arthritis-ameliorating efficacy of NADPH oxidaseactivating compounds. To obtain a more detailed understanding of the molecular mechanism of this regulation, gene-expression profiling experiments were performed on inguinal lymph nodes from rats with pharmacologically (phytol) and genetically (Ncf1) modified NADPH oxidase activity. In this study, we used global gene-expression analysis and quantitative real-time PCR techniques in four separate arthritis experiments in rats to investigate the downstream effects of preventive arthritis treatment with the NADPH oxidase activator phytol. cache = ./cache/cord-328804-f7etlk5i.txt txt = ./txt/cord-328804-f7etlk5i.txt === reduce.pl bib === id = cord-329366-xuszdrsa author = Hackbart, Matthew title = Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors date = 2020-04-07 pages = extension = .txt mime = text/plain words = 7187 sentences = 445 flesch = 57 summary = In this study, we show that CoV EndoU activity limits the abundance and length of the polyuridine (polyU) extension on 5′-polyU-containing, negative-sense (PUN) RNAs for both the beta-CoV mouse hepatitis virus strain A59 (MHV-A59) and the alpha-CoV PEDV. Overall, we propose a mechanism for EndoU, which is to cleave polyU sequences from PUN RNAs, thus limiting the formation of a PAMP and impeding the ability of MDA5 to activate the innate immune response to infection. EndoU Activity Limits Abundance and Length of PUN RNAs. Previous studies showed that the 5′ end of the CoV negative-sense RNA contains polyU extensions (35) , and that EndoU cleaves at uridine residues (22, 25, (27) (28) (29) (30) . We found that the products generated from positive-sense RNA were similar between wild-type and EndoUmut viruses, consistent with our previous results indicating that the polyA tail is not cleaved by EndoU activity (Fig. 5C ). cache = ./cache/cord-329366-xuszdrsa.txt txt = ./txt/cord-329366-xuszdrsa.txt === reduce.pl bib === === reduce.pl bib === id = cord-327855-txryqil7 author = Kulka, M. title = The cytopathic 18f strain of Hepatitis A virus induces RNA degradation in FrhK4 cells date = 2003 pages = extension = .txt mime = text/plain words = 8706 sentences = 394 flesch = 50 summary = Analysis of total cellular RNA from HM175/18f infected FrhK4 cells by denaturing agarose gel electrophoresis and Northern blot hybridization revealed extensive degradation of both the 28S and 18S ribosomal RNA (rRNA) molecules. In this study, we report that infection of FrhK4 cells with the HAV cp strain HM175/18f results in the degradation of ribosomal RNA (rRNA) and the reduction of several cellular mRNAs including β-actin and GAPDH. Degradation of rRNA is a feature of virus infection in interferon (IFN) treated cells and is believed to be due to the availability of double stranded RNA (dsRNA) during replication or transcription of the viral genome, resulting in the activation of the RNase L pathway [58, 59] . While the role of a viral protein in the activation of 2-5A/RNase L pathway in 18f or CBV1 infected FrhK4 cells cannot be ruled out, previous reports with EMC virus and the studies involving dsRNA clearly suggests a similar mechanism of rRNA degradation reported here. cache = ./cache/cord-327855-txryqil7.txt txt = ./txt/cord-327855-txryqil7.txt === reduce.pl bib === id = cord-329190-kv9n2qj3 author = Rabaan, Ali A. title = A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective date = 2017-09-01 pages = extension = .txt mime = text/plain words = 8886 sentences = 433 flesch = 44 summary = The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The Medline database was searched using combinations and variations of terms, including 'Middle East respiratory syndrome coronavirus', 'MERS-CoV', 'SARS', 'therapy', 'molecular', 'vaccine', 'prophylactic', 'S protein', 'DPP4', 'heptad repeat', 'protease', 'inhibitor', 'anti-viral', 'broad-spectrum', 'interferon', 'convalescent plasma', 'lopinavir ritonavir', 'antibodies', 'antiviral peptides' and 'live attenuated viruses'. A position paper on the evidence base for specific MERS-CoV therapies, published by Public Health England (PHE) and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO), suggested that benefit was likely to exceed risk for convalescent plasma, lopinavir-ritonavir, IFNs and monoclonal/polyclonal antibodies, while, by contrast, for ribavirin monotherapy and corticosteroids it was considered that the risks would outweigh the benefits [42] . cache = ./cache/cord-329190-kv9n2qj3.txt txt = ./txt/cord-329190-kv9n2qj3.txt === reduce.pl bib === id = cord-328947-3l9ydspz author = Webb, L. G. title = Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date = 2020-10-15 pages = extension = .txt mime = text/plain words = 9857 sentences = 544 flesch = 51 summary = CHIKV is no exception, the type-I interferon (IFN) response has been demonstrated to be key in controlling CHIKV infection [21] [22] [23] [24] [25] [26] and primary sensing of the virus is via the pattern recognition receptor (PRR) retinoic acid-inducible gene I (RIG-I)-mitochondrial antiviral signaling protein (MAVS) axis [24, 26] . The lack of cGAS degradation seen in the exogenous expression system when compared to the infected cells shows that although there is a clear interaction of cGAS with nsP4, the degradation of cGAS observed is not mediated by the non-structural proteins of CHIKV, but must require other viral or host factors. Chikungunya virus inhibits DNA sensing by degrading cGAS both mock and infected cells by 4 hpi suggesting that the stress produced during the process of infection (mock or CHIKV) in HFF-1s stimulates increased translation at early timepoints ( Fig 4D, lanes 2 and 5) . cache = ./cache/cord-328947-3l9ydspz.txt txt = ./txt/cord-328947-3l9ydspz.txt === reduce.pl bib === id = cord-327135-4c2flue4 author = Chinnaswamy, S title = Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections date = 2016-06-09 pages = extension = .txt mime = text/plain words = 9813 sentences = 499 flesch = 48 summary = Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. Three independent groups conducted genome-wide association studies (GWASs) involving treatment response to chronic hepatitis C virus (HCV) infections, in three different geographical regions of the world, and reported that single-nucleotide polymorphisms (SNPs) in the IFNL locus (Figure 1 ), had strong association with treatment-induced HCV clearance irrespective of ethnicity and geographical location of the hosts. 49 In stark contrast, a dominant model of inheritance (of the non-beneficial IFNL SNP minor allele) has consistently given the best explanation on the observed phenotypes in association studies with both spontaneous clearance and IFN-based treatment response in chronic HCV infections. cache = ./cache/cord-327135-4c2flue4.txt txt = ./txt/cord-327135-4c2flue4.txt === reduce.pl bib === id = cord-332154-2gej7h1d author = Meier, William A. title = Cytokines and synthetic double-stranded RNA augment the T helper 1 immune response of swine to porcine reproductive and respiratory syndrome virus date = 2004-12-08 pages = extension = .txt mime = text/plain words = 9170 sentences = 415 flesch = 46 summary = Immunization of pigs with a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine initially elicits a weak interferon (IFN)-γ response. Based on the success of this intervention and the noted absence of IFN-a generation during PRRSV infection, the present studies were undertaken to determine if the antiviral adaptive immunity induced by vaccination with PRRS MLV could be modified simply by the co-administration of rIL-12 protein directly, or of either porcine IFN-a or IL-12 indirectly via plasmids expressing these cytokines. Although a similar response was evident during this time period for vaccinated pigs also i.m. injected with exogenous IL-12 either directly as protein or indirectly via IL-12 cDNA, immunized animals that were i.d. inoculated with IL-12 cDNA exhibited an overall 2.7-fold transient increase in the frequency of PRRSV-specific IFN-g SC at 2 weeks post-vaccination. Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) cache = ./cache/cord-332154-2gej7h1d.txt txt = ./txt/cord-332154-2gej7h1d.txt === reduce.pl bib === id = cord-333208-tibtngy8 author = Muñoz-Moreno, Raquel title = Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection date = 2016-04-26 pages = extension = .txt mime = text/plain words = 5867 sentences = 311 flesch = 45 summary = The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV. Thus, our goal in the current work was to test whether the IFITM family of proteins affected early entry steps of ASFV infection in Vero cell cultures using the cell-adapted Ba71V isolate. Confocal microscopy experiments revealed that, IFITM1 was mainly distributed at the plasma membrane and to a lesser extent in perinuclear compartments, resembling endosomal structures (Fig 3C, lower left panel) , while endogenous IFITM1 was barely detected in Vero cells containing the empty vector (Fig 3C, upper left panel) . cache = ./cache/cord-333208-tibtngy8.txt txt = ./txt/cord-333208-tibtngy8.txt === reduce.pl bib === === reduce.pl bib === id = cord-333650-4towah1t author = Malmo, Jostein title = Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date = 2016-05-12 pages = extension = .txt mime = text/plain words = 4659 sentences = 250 flesch = 50 summary = Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. To determine the presence of antiviral cytokines in children infected with hMPV and controls, we initially investigated the expression of type I, II and III IFNs. Fig 1A shows that only A2 infected children had slightly elevated mRNA levels of the type I IFN-β compared to the controls. Fig 2 shows the mRNA expression of A) IκBα, a repressor gene induced by NF-κB activation [19] , B) IL-1β, C) IL-18 and D) NLRP3 in hMPV infected children and controls. A previous study comparing the expression of several inflammatory cytokines in hMPV, RSV and influenza virus, detected elevated levels of TNF-α, IL-6 and IL-1β protein in nasal washes from infants with RTI [9] . cache = ./cache/cord-333650-4towah1t.txt txt = ./txt/cord-333650-4towah1t.txt === reduce.pl bib === id = cord-333955-bnzbppof author = Biesold, Susanne E. title = Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum date = 2011-11-30 pages = extension = .txt mime = text/plain words = 5016 sentences = 275 flesch = 51 summary = Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. Cells from Pteropus species have been shown to produce high amounts of interferon (IFN)-l after stimulation with the double-strand (ds)RNA analogue poly IC, and after infection with the bat-associated paramyxovirus, Tioman [13] . In accordance with the IFN mRNA induction, the highest equivalent amount of bioactive secreted IFN upon RVFV 13 virus infection and poly IC transfection was measured in EidNi/41.3 cells, followed by MEF and MA104 (Figure 3 ). Increases of infectious virus formation were about 1000-fold within 24 hpi, and specific infectivities, expressed as PFU per genome equivalent (PCR units), were highly comparable between cell cultures ( Figure 4C) . cache = ./cache/cord-333955-bnzbppof.txt txt = ./txt/cord-333955-bnzbppof.txt === reduce.pl bib === id = cord-327000-oyg3oyx1 author = Li, Shasha title = Porcine Epidemic Diarrhea Virus and the Host Innate Immune Response date = 2020-05-11 pages = extension = .txt mime = text/plain words = 11098 sentences = 688 flesch = 48 summary = This review highlights the immune evasion mechanisms employed by PEDV, which provides insights for the better understanding of PEDV-host interactions and developing effective vaccines and antivirals against CoVs. Porcine epidemic diarrhea virus (PEDV) is the etiological agent of porcine epidemic diarrhea (PED) that causes an acute and highly contagious enteric disease of swine characterized by vomiting, diarrhea, dehydration, and anorexia in pigs of all ages, especially resulting in severe diarrhea and high mortality rate in piglets. Nsp3 is the largest nsp protein, containing two papain-like protease (PLP1 and PLP2) domains, of which PEDV PLP2 acts as a viral deubiquitinase (DUB), to negatively regulate type I IFN signaling [80] . The evasive strategies utilized by PEDV are classified into four major types: (1) inhibition of RLRs-mediated IFN production pathways, (2) inhibition of the activation of transcription factors responsible for IFN induction, (3) disruption of the signal cascades induced by IFN, and (4) hiding its viral RNA to avoid the exposure of viral RNA to immune sensors. cache = ./cache/cord-327000-oyg3oyx1.txt txt = ./txt/cord-327000-oyg3oyx1.txt === reduce.pl bib === id = cord-334510-37g8zxne author = Jartti, T. title = Distinct regulation of tonsillar immune response in virus infection date = 2014-03-29 pages = extension = .txt mime = text/plain words = 4177 sentences = 251 flesch = 42 summary = OBJECTIVE: To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T‐cell‐ and innate immune response‐specific cytokines, transcription factors, and type I/II/III interferons in human tonsils. Conclusions: Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes. Conclusions: Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes. Studies in adults have shown an association between persistent/latent Abbreviations AdV, adenovirus; BoV, bocavirus-1; CT, cycle threshold; CV, coronavirus; EF1-a, elongation factor-1a; EV, enteroviruses; FOXP3, forkhead box protein 3; Flu, influenza A or B virus; IFN, interferon; IL, interleukin; MPV, metapneumovirus; PBMC, peripheral blood mononuclear cells; PCR, polymerase chain reaction; PIV, parainfluenza virus types 1-4; RORC2, retinoic acid receptor-related orphan receptor C2; RSV, respiratory syncytial virus; RV, rhinovirus; suppl., supplementary; Th, T helper cell; TGF-b, transforming growth factor-b. cache = ./cache/cord-334510-37g8zxne.txt txt = ./txt/cord-334510-37g8zxne.txt === reduce.pl bib === id = cord-333463-u7je0d1o author = Diaz-Salazar, Carlos title = Natural killer cell responses to emerging viruses of zoonotic origin date = 2020-08-09 pages = extension = .txt mime = text/plain words = 6193 sentences = 353 flesch = 43 summary = Nearly all emerging viruses, including Ebola, Dengue, Nipah, West Nile, Zika, and coronaviruses (including SARS-Cov2, the causative agent of the current COVID-19 pandemic), have zoonotic origins, indicating that animal-to-human transmission constitutes a primary mode of acquisition of novel infectious diseases. Natural killer (NK) cells are innate lymphocytes that play a critical role in the early antiviral response, secreting effector cytokines and clearing infected cells. This review describes the role of Natural killer (NK) cells, a critical component of early antiviral immunity, in the establishment of tolerance to viral infections in natural hosts, as well as their role in the development of disease in nonnatural hosts. Altogether, it is believed that quick control of viral infections and reduced induction of pro-inflammatory cytokines have allowed bat viruses to rapidly co-evolve with their host without provoking major immuneThe careful study of the immune system in reservoirs of zoonotic diseases will certainly offer insights into how these animals carry high viral loads while remaining asymptomatic. cache = ./cache/cord-333463-u7je0d1o.txt txt = ./txt/cord-333463-u7je0d1o.txt === reduce.pl bib === id = cord-332632-u2ud0vmq author = Lussi, Carmela title = What can pestiviral endonucleases teach us about innate immunotolerance? date = 2016-03-17 pages = extension = .txt mime = text/plain words = 8703 sentences = 394 flesch = 44 summary = In particular, the unique extension of 'self' to include the viral genome by degrading immunostimulatory viral RNA by E(rns) is reminiscent of various host nucleases that are important to prevent inappropriate IFN activation by the host's own nucleic acids in autoimmune diseases such as Aicardi-Goutières syndrome or systemic lupus erythematosus. Thus, the survival strategy of BVDV consists of being non-cytopathogenic and producing less dsRNA than its cp counterpart, and expressing the IFN antagonists N pro as the first protein in order to reduce or even avoid IFN production in infected cells and E rns to degrade immunostimulatory viral RNA before they might activate the host's PRRs. Notably, both pestiviral IFN antagonists are not only required to constantly maintain innate immunotolerance during persistent infections, but they also play an important role in acute infections [25] . cache = ./cache/cord-332632-u2ud0vmq.txt txt = ./txt/cord-332632-u2ud0vmq.txt === reduce.pl bib === id = cord-337285-t6qr41wc author = Ikeda, Masanori title = Modulation of host metabolism as a target of new antivirals() date = 2007-10-10 pages = extension = .txt mime = text/plain words = 8180 sentences = 466 flesch = 46 summary = Using cell culture systems, several cellular proteins have been identified as effective molecules for HCV RNA replication (Table 1) . [66] reported that lovastatin (LOV), one of the HMG-CoA reductase inhibitors, inhibited HCV RNA replication in HCV replicon-harboring cells. Depletion of the GGPP by statins may inhibit the geranylgeranylation of cellular proteins such as FBL2 and cause the anti-HCV effect in the cells. During the development of IFN therapy for patients with CH-C, the lack of a robust method of HCV RNA replication in cell culture has hampered research into the HCV life cycle and the discovery of potent new anti-HCV reagents. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells cache = ./cache/cord-337285-t6qr41wc.txt txt = ./txt/cord-337285-t6qr41wc.txt === reduce.pl bib === === reduce.pl bib === id = cord-333423-jhm7u8ka author = Wang, Dang title = Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Type I Interferon Signaling by Targeting IRF9 date = 2019-05-15 pages = extension = .txt mime = text/plain words = 7204 sentences = 390 flesch = 48 summary = Furthermore, the nsp11-IRF9 interaction impaired the formation and nuclear translocation of the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) in both nsp11-overexpressed and PRRSV-infected cells. Taking the results together, our study demonstrated that PRRSV nsp11 antagonizes type I IFN signaling by targeting IRF9 via a NendoU activity-independent mechanism, and this report describes a novel strategy evolved by PRRSV to counteract host innate antiviral responses, revealing a potential new function for PRRSV nsp11 in type I IFN signaling. The type I IFN-activated ISGF3 transcription complex containing tyrosine-phosphorylated STAT1 and STAT2 associated with IRF9 is rapidly translocated to the nucleus FIG 3 PRRSV nsp11 inhibits ISGF3-induced ISRE promoter activity. This provided further support for the notion that the ability of PRRSV nsp11 to block type I IFN signaling is independent of its endoribonuclease activity and cell cytotoxicity, because these three mutants had similar effects with respect to inhibiting the formation and nuclear translocation of ISGF3 compared with WT nsp11. cache = ./cache/cord-333423-jhm7u8ka.txt txt = ./txt/cord-333423-jhm7u8ka.txt === reduce.pl bib === id = cord-335245-1eksm537 author = Pattyn, Els title = HyperISGylation of Old World Monkey ISG15 in Human Cells date = 2008-06-18 pages = extension = .txt mime = text/plain words = 7011 sentences = 419 flesch = 54 summary = Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Western blot analysis on total cell lysates containing b-ME confirmed ISGylation of UbcH10, H13 and H17 with AgmISG15 but not with HuISG15, as seen by a 15 kDa shift upon staining with anti-V5 Ab detecting the ectopic expressed UbcH proteins (Figure 3a ,b and Figure S2a ). Previous studies using Western blot analysis in HekT cells revealed Hu or MoISG15 conjugation to substrates such as UbcH13 only upon co-transfection of at least UbE1L -and generally also UbcH/M8or upon IFN stimulation. The effect of mutating HuISG15 residues situated near the predicted UbE1L interface and the different allelic variants on conjugation to UbcH proteins is shown in Figure 5a and S3a. As shown in Figure 5c , mutation of D133N and QIT31-33KIA in the HuISG15 N89D variant further enhanced its ISGylation in human HekT cells. cache = ./cache/cord-335245-1eksm537.txt txt = ./txt/cord-335245-1eksm537.txt === reduce.pl bib === id = cord-329618-kywhulpc author = Xu, Cheng title = A de novo transcriptome analysis shows that modulation of the JAK-STAT signaling pathway by salmonid alphavirus subtype 3 favors virus replication in macrophage/dendritic-like TO-cells date = 2016-05-23 pages = extension = .txt mime = text/plain words = 8323 sentences = 426 flesch = 55 summary = To elucidate the effect of type I IFN on the Jak/stat pathway in salmonid alphavirus subtype 3 (SAV3) infected macrophage/dendritic like TO-cells derived from Atlantic salmon (Salmo salar L) headkidney leukocytes, we used a differential transcriptome analysis by RNA-seq and the Kyoto encyclopedia of genes and genomes (KEGGs) pathway analysis to generate a repertoire of de novo assembled genes from type I IFN treated and non-treated TO-cells infected with SAV3. CONCLUSION: Data presented in this study shows that SAV3 infection downregulates several genes of the Jak/stat pathway, which could be an immune evasion strategy, used to block the transcription of antiviral genes that would interfere with SAV3 replication in TO-cells. Hence, in this study we used the KEGG pathway analysis software which is a third generation PT based software to identify networks of genes that form the Jak/stat signaling pathway from a de novo assembled transcriptome with the aim to better understand the modulation of genes expressed by TO cells infected with SAV3. cache = ./cache/cord-329618-kywhulpc.txt txt = ./txt/cord-329618-kywhulpc.txt === reduce.pl bib === id = cord-334134-fhie2m3u author = Mazaleuskaya, Liudmila title = Protective Role of Toll-like Receptor 3-Induced Type I Interferon in Murine Coronavirus Infection of Macrophages date = 2012-05-24 pages = extension = .txt mime = text/plain words = 7171 sentences = 496 flesch = 59 summary = We assessed the effect of triggering TLR2, TLR3, TLR4, and TLR7 with selected ligands on the susceptibility of the J774A.1 macrophage cell line to infection with murine coronavirus (mouse hepatitis virus, [MHV]). These results together with the antiviral effect of poly I:C (Figure 3 ) suggested that the protective role of TLR3 against coronavirus infection in J774A.1 macrophages may be mediated by type I IFN. We hypothesized that the differential effect of TLR ligands on MHV production is due to their variable ability to induce type I IFN crucial for triggering an "antiviral state" and protecting cells from virus infection [26, 38] . In the present study prestimulation of J774A.1 macrophages with poly I:C, a potent type I IFN inducer, resulted in a strong IFN-β response that triggered antiviral immunity and protected macrophages from MHV infection before and after virus adsorption. cache = ./cache/cord-334134-fhie2m3u.txt txt = ./txt/cord-334134-fhie2m3u.txt === reduce.pl bib === id = cord-337717-8hcujmuo author = Savarin, Carine title = IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils date = 2012-05-29 pages = extension = .txt mime = text/plain words = 6901 sentences = 372 flesch = 44 summary = CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT) or IFN-γ deficient (GKO) memory CD4(+) T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade. RESULTS: Transfer of GKO memory CD4(+) T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4(+) T cells, despite similar virus control and demyelination. Overall these data confirm IFN-γ-mediated control of CNS neutrophil infiltration and suggested a protective role of IFN-γ during viral encephalitis, via inhibiting IL-17 effector function by either directly reducing Th17 cell expansion and/or CNS entry, or limiting GM-CSF production. Although GM-CSF expression is reduced by IFN-γ [27] , the data do not support a pathogenic role of GM-CSF in early mortality of JHMV-infected GKO recipients. cache = ./cache/cord-337717-8hcujmuo.txt txt = ./txt/cord-337717-8hcujmuo.txt === reduce.pl bib === id = cord-338602-6n309bnp author = Gadotti, Ana Carolina title = IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection date = 2020-09-23 pages = extension = .txt mime = text/plain words = 2888 sentences = 183 flesch = 53 summary = title: IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors. A reasonable hypothesis is that (i) pro-inflammatory innate immunity and (ii) anti-inflammatory system are related to disease severity or death once IL-6, IL-8, and IL10 are closely described as prognostic factors in patients diagnosed with COVID-19 1, 3, 7 . Previous studies have not reported the association between IFN-γ and death, even evaluating the COVID-19-reactive CD69+ expressing IFN-γ producing CD8+ T in 25 patients with severe and moderate disease 22 . Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan Levels of cytokines from patients with moderate and severe COVID-19 infection according to the outcome (data in the median with IQR) cache = ./cache/cord-338602-6n309bnp.txt txt = ./txt/cord-338602-6n309bnp.txt === reduce.pl bib === id = cord-333600-k6ws97at author = Mihm, Sabine title = COVID-19: Possible Impact of the Genetic Background in IFNL Genes on Disease Outcomes date = 2020-04-28 pages = extension = .txt mime = text/plain words = 684 sentences = 42 flesch = 48 summary = Host control of MHV infection is completely dependent on TLR7 triggering by viral RNA causing an immediate interferon (IFN) response [2] . Sex differences in TLR7 responses have been reported for humans -with female sex better coping with viral infection [4] [5] [6] -which is also a feature of COVID-19. Upon binding viral nucleic acid motifs, TLR7 induces the expression of type I IFNs (IFN-α and IFN-β) and the expression of the more recently described family of type III IFNs (IFN-λ [1] [2] [3] [4] . A common germ line genetic variation within the type III IFN gene locus has been most convincingly shown to determine the host's capacity to cope with an infection induced by hepatitis C virus (HCV), an enveloped ssRNA virus of positive orientation, too, featuring tropism for liver epithelial cells. CD200 receptor controls sex-specific TLR7 responses to viral infection IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes cache = ./cache/cord-333600-k6ws97at.txt txt = ./txt/cord-333600-k6ws97at.txt === reduce.pl bib === id = cord-341324-f9g9gitn author = Rojas, José M. title = Viral pathogen-induced mechanisms to antagonize mammalian interferon (IFN) signaling pathway date = 2020-10-21 pages = extension = .txt mime = text/plain words = 10837 sentences = 595 flesch = 42 summary = This includes for instance cooperating in PRR recognition of viral PAMPs, stabilizing signaling complexes to improve their resistance to degradation, stopping virus entry, blocking viral capsid formation, impairing trafficking and budding of virions from the infected cells, but also modulating the IFN response to avoid the toxicity of these potent immune mediators. The phosphorylated STAT1/STAT2 heterodimer associates with interferon regulatory factor 9 (IRF9) to form the transcriptional factor complex ISGF3, which translocate to the nucleus and binds the IFN-response elements (ISRE) in ISG promoters leading to the expression of ISG products [36] (Fig. 2 The oligoadenylate synthetase (OAS)-latent RNase (RNase L) pathway is another IFN-inducible pathway that provides the cell with an effector mechanism upon recognition of viral dsRNA (reviewed in [44] ). cache = ./cache/cord-341324-f9g9gitn.txt txt = ./txt/cord-341324-f9g9gitn.txt === reduce.pl bib === id = cord-338320-jc00ulx5 author = Siu, Kam-Leung title = Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain date = 2014-02-10 pages = extension = .txt mime = text/plain words = 3684 sentences = 238 flesch = 53 summary = title: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 12 , 13 We have previously reported that SARS coronavirus M protein suppresses type I IFN production potently by preventing the formation of functional TRAF3-TANK-TBK1/IKKe complex. IFN antagonism of SARS coronavirus M protein was mediated by N-terminal TM1 (amino acids 1-38), which targets M protein to the Golgi complex and associates with TRAF3 to prevent it from interacting with TANK, TBK1 and IKKe. Our findings provide additional molecular details for suppression of type I IFN production by SARS coronavirus M protein. Notably, human coronavirus HKU1 M protein also targets the Golgi complex, interacts with TRAF3, but does not suppress IFN production. cache = ./cache/cord-338320-jc00ulx5.txt txt = ./txt/cord-338320-jc00ulx5.txt === reduce.pl bib === id = cord-337365-hugenn14 author = Chen, Zhuangzhuang title = The role of microglia in viral encephalitis: a review date = 2019-04-09 pages = extension = .txt mime = text/plain words = 7265 sentences = 391 flesch = 38 summary = Microglia can exert a direct antiviral effect by producing type 1 interferon (IFN-1) to induce IFN-stimulated gene (ISG) expression of themselves or indirect antiviral effects by IFN-1 acting on other cells to activate corresponding signaling pathways. In a mouse model of West Nile virus (WNV) infection, it was found that the permeability of the BBB increased in mice lacking IFNAR, especially in the hindbrain, which leads to an increase in viral entry, indicating that IFNAR signaling has important regulatory effects on BBB permeability in this brain region. Loss of astrocyte IFNAR signaling pathway can cause a variety of consequences, including increased expression of inflammatory cytokines and chemokines, which disrupt the blood-brain barrier during neurotropic viral infection [30] . In a mouse model of lethal West Nile virus (WNV) infection, Peli1 promotes the production of pro-inflammatory cytokines and chemokines in microglia and promotes the entry of T cells and macrophages into the CNS. cache = ./cache/cord-337365-hugenn14.txt txt = ./txt/cord-337365-hugenn14.txt === reduce.pl bib === id = cord-340422-8f5xe4zc author = Rowland, R. R. R. title = Inhibition of porcine reproductive and respiratory syndrome virus by interferon-gamma and recovery of virus replication with 2-aminopurine date = 2001 pages = extension = .txt mime = text/plain words = 4715 sentences = 283 flesch = 50 summary = Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to a group of RNA viruses that establish persistent infections. IFN-γ mRNA expression was observed in the lymph nodes and lungs of pigs infected with wild-type PRRSV strain SDSU-23983. The purpose of this study was to evaluate the production of IFN-␥ in pigs following infection with PRRSV and to characterize the mechanism of IFN-␥ action following infection of MARC-145 cells with wild-type and culture adapted PRRSV isolates. The results show that IFN-␥ efficiently inhibits PRRSV replication in MARC-145 cells, and at least part of the antiviral activity may be through PKR. IFN-␥ mRNA expression was detected in the lymph nodes from two of the 3 pigs infected with the wild-type P6 virus (Fig. 1) . Consistent with other reports describing the presence of cell-mediated immunity during PRRSV infection [4, 31] , we observed IFN-␥ mRNA expression in lymph nodes and lungs of PRRSV-infected pigs (Fig. 1) . IFN gamma inhibits porcine reproductive and respiratory syndrome virus replication in macrophages cache = ./cache/cord-340422-8f5xe4zc.txt txt = ./txt/cord-340422-8f5xe4zc.txt === reduce.pl bib === id = cord-342189-ya05m58o author = Banerjee, Abhik K. title = SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses date = 2020-10-08 pages = extension = .txt mime = text/plain words = 11469 sentences = 647 flesch = 55 summary = Here, we comprehensively define the interactions between each SARS-CoV-2 protein and human RNAs. We show that 10 viral proteins form highly specific interactions with mRNAs or ncRNAs, including those involved in progressive steps of host cell protein production. We show J o u r n a l P r e -p r o o f 5 that NSP16 binds to the mRNA recognition domains of the U1 and U2 RNA components of the spliceosome and acts to suppress global mRNA splicing in SARS-CoV-2-infected human cells. We identified several pathogenic functions of SARS-CoV-2 in human cells -including global inhibition of host mRNA splicing, protein translation, and membrane protein trafficking -and described the molecular mechanisms by which the virus acts to disrupt these essential cell processes. cache = ./cache/cord-342189-ya05m58o.txt txt = ./txt/cord-342189-ya05m58o.txt === reduce.pl bib === id = cord-344798-q34j4zxu author = Villalba, María Caridad Montalvo title = Interferon gamma, TGF-β1 and RANTES expression in upper airway samples from SARS-CoV-2 infected patients date = 2020-08-29 pages = extension = .txt mime = text/plain words = 4141 sentences = 232 flesch = 44 summary = title: Interferon gamma, TGF-β1 and RANTES expression in upper airway samples from SARS-CoV-2 infected patients The aim of this study was evaluate inflammatory response using the expression of immune mediators with antiviral, immunosuppression and chemotactic functions in the primary site of SARS-CoV-2 replication, at early stage of infection. J o u r n a l P r e -p r o o f Taking into account that Ct value has a correlation with the amount of RNA present in the samples, it was found that medians and IQR of SARS-CoV-2 viral titer was similar in asymptomatic (33.00, 29.00-37.00) and symptomatic (30, 27 .00-37.00) cases; and comparison between groups did not show difference (p=0.4373). As show our results, SARS-CoV-2 infection induced high IFN-γ expression in swabbed cells from upper airway; its expression was higher in symptomatic patients in comparison with asymptomatic individuals. Also, positive correlation between IFN-γ and TGF-β1 provided evidence of immune response control could determinate the asymptomatic presentation of SARS-CoV-2 infection. cache = ./cache/cord-344798-q34j4zxu.txt txt = ./txt/cord-344798-q34j4zxu.txt === reduce.pl bib === id = cord-340475-h0q1m3ed author = Carnero, Elena title = Type I Interferon Regulates the Expression of Long Non-Coding RNAs date = 2014-11-06 pages = extension = .txt mime = text/plain words = 10164 sentences = 544 flesch = 55 summary = Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response.These genes are induced in response to different doses of IFNα2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. HuH7 cells were treated for 6, 24, 48, or 72 h with increasing doses of IFNα2 up to 10,000 units/ml, and the expression levels of GBP1, IRF1, BST2, OAS, IL6, and ISG15 were evaluated by qRT-PCR (Figure 1) . cache = ./cache/cord-340475-h0q1m3ed.txt txt = ./txt/cord-340475-h0q1m3ed.txt === reduce.pl bib === id = cord-337677-ktktqs7b author = Pereda, R. title = Therapeutic effectiveness of interferon alpha 2b treatment for COVID-19 patient recovery date = 2020-08-04 pages = extension = .txt mime = text/plain words = 3397 sentences = 212 flesch = 54 summary = Patients received therapy as per the Cuban COVID protocol that included a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN alpha-2b The primary endpoint was the proportion of patients discharged from hospital, secondary was the case fatality rate and several outcomes related to time variables were also evaluated. Two groups of individuals were admitted to the hospital, according to the case classification criteria defined in the Cuban protocol: 1) people with suspected COVID-19 due to clinical respiratory symptoms, such as fever, fatigue, cough, headache, shortness of breath and nasal discharge in the last 14 days; 2) subjects who had contact with a patient with confirmed or is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint cache = ./cache/cord-337677-ktktqs7b.txt txt = ./txt/cord-337677-ktktqs7b.txt === reduce.pl bib === id = cord-343221-e29of29o author = Kindler, Eveline title = Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication date = 2017-02-03 pages = extension = .txt mime = text/plain words = 7896 sentences = 423 flesch = 51 summary = Specifically, we show that genetically engineered mutants of mouse hepatitis virus (MHV) and human coronavirus 229E (HCoV-229E), respectively, that encode an EndoU active-site substitution known to abolish nucleolytic activity, were severely attenuated and elicited an immediate and simultaneous activation of host cell dsRNA sensors. The severe attenuation of MHV H277A and HCoV-229E H250A replication in wild-type murine and human macrophages, respectively, precluded the use of primary macrophages to assess the sensitivity of EndoU-deficient coronaviruses to IFN-I pre-treatment. Our data suggest that direct restriction of replication of EndoU-deficient coronaviruses is mediated by RNase L-mediated RNA degradation and inhibition of host cell translation through activation of PKR. Notably, also in this case Xrn1 is required to further process the de-capped mRNAs. Our data show that early during coronavirus infection the EndoU activity conceptually fulfils the same task, namely the removal of dsRNA that would otherwise trigger host cell dsRNA responses, such as IFN-β expression and activation of PKR and OAS/RNase L. cache = ./cache/cord-343221-e29of29o.txt txt = ./txt/cord-343221-e29of29o.txt === reduce.pl bib === id = cord-334624-chnibsa1 author = Hayn, Manuel title = Imperfect innate immune antagonism renders SARS-CoV-2 vulnerable towards IFN-γ and -λ date = 2020-10-30 pages = extension = .txt mime = text/plain words = 5355 sentences = 432 flesch = 57 summary = Here, we systematically assessed the impact of 29 SARS-CoV-2 proteins on viral sensing, type I, II and III interferon (IFN) signaling, autophagy and inflammasome formation. Our results identify ineffective type I and II antagonism as weakness of SARS-CoV-2 that may allow to devise safe and effective anti-viral therapies based on targeted innate immune activation. SARS-CoV-1 ORF6 is about 4-fold less potent in antagonizing type I IFN signaling (Fig. 243 4b) but induces higher levels of autophagy (Fig. 4c) . Examination of the functional conservation showed that SARS-CoV-2 Nsp15 was less 319 efficient in blocking innate immune activation, both type I IFN induction and signaling, than SARS-320 Hepatitis C virus viruses to block anti-viral autophagic turnover 50 and thus may represent a common studies will see more mechanistic data to explain the molecular details of the impact of SARS-CoV-2 343 proteins on innate immune activation. cache = ./cache/cord-334624-chnibsa1.txt txt = ./txt/cord-334624-chnibsa1.txt === reduce.pl bib === id = cord-343824-00mqmpzw author = Qian, Wei title = The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3 date = 2017-07-03 pages = extension = .txt mime = text/plain words = 6217 sentences = 333 flesch = 50 summary = title: The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3 Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. Hence, binding of the NS1 protein to dsRNA, RIG-I, and TRIM25 has not established that these NS1 interactions are responsible for inhibiting the activation of IRF3 and IFN transcription. These data reveal a novel mechanism for how the influenza A virus NS1 protein induces inhibition of the host IFN production and may provide a potential target for antiviral drug development. However, our study demonstrated that the influenza A virus NS1 ED targets TRAF3, subsequently inhibits IFN production, implying that TRAF3 is a key factor involved for IAV to escape host innate immune responses. cache = ./cache/cord-343824-00mqmpzw.txt txt = ./txt/cord-343824-00mqmpzw.txt === reduce.pl bib === id = cord-343515-fad1yyqx author = Felgenhauer, Ulrike title = Inhibition of SARS–CoV-2 by type I and type III interferons date = 2020-10-09 pages = extension = .txt mime = text/plain words = 2934 sentences = 157 flesch = 53 summary = For SARS-CoV-2 (dark gray bars), statistically significant negative correlation coefficients (CC) were obtained for both cell lines, indicating that viral replication is increasingly inhibited by IFN-a. Observations were similar when the input MOI was reduced to 0.001 (Fig. S1 ), except that titers of SARS-CoV-1 in Calu-3 cells were already very low in the absence of any IFN-a, resulting in a nonsignificant effect of additional IFN. Our data thus indicate that (i) if anything, ruxolitinib is an enhancer rather than an inhibitor of SARS-CoV-2 multiplication, and (ii) the boosting effect is most likely due to inhibition of the antiviral JAK/ STAT signaling pathway, because it is not present in the IFN induction-deficient Vero E6 cells. For the statistical testing of the dose-response effect of IFN (type I and III) against SARS-coronaviruses, the typical regression procedures were not applicable because of several values below the detection limit and some ties in the data. cache = ./cache/cord-343515-fad1yyqx.txt txt = ./txt/cord-343515-fad1yyqx.txt === reduce.pl bib === id = cord-341278-klv9jdm8 author = Smith, Abigail L. title = The role of gamma interferon in infection of susceptible mice with murine coronavirus, MHV-JHM date = 1991 pages = extension = .txt mime = text/plain words = 3861 sentences = 182 flesch = 45 summary = Infection of BALB/c mice with mouse hepatitis virus, strain JHM (MHV-JHM), at any of several intervals relative to ovalbumin (OVA) administration resulted in elevated OVA-specific IgG 2 a titers. Serum IFN-γ was not detected, but treatment of MHV-JHM-infected mice with monoclonal anti-IFN-γ antibody resulted in high mortality with decreased survival times, enhanced virus titers in liver and spleen, and more severe virus-associated pathology, compared to mock-treated, infected mice. Sera from mice infected with MHV-JHM one day prior to OVA administration contained substantially elevated levels of antigen-specific IgG2 a on day 7 (Table 1 ) with geometric mean titers that were 17 times control (OVA only) values at that interval. The elevated IgG 2 a OVA-specific response of most groups of MHV-infected mice and the preferential production of this isotype by mice infected one day prior to antigen administration suggested that these mice were producing IFNy. However, using the WEHI 279 B cell lymphoma bioassay [24] , attempts to detect the cytokine in sera of infected mice failed, as had earlier attempts to 27] . cache = ./cache/cord-341278-klv9jdm8.txt txt = ./txt/cord-341278-klv9jdm8.txt === reduce.pl bib === === reduce.pl bib === id = cord-353957-0pjg25kn author = Chen, Shilong title = Avian Interferon-Inducible Transmembrane Protein Family Effectively Restricts Avian Tembusu Virus Infection date = 2017-04-20 pages = extension = .txt mime = text/plain words = 6563 sentences = 381 flesch = 53 summary = Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV infection can effectively restrict the virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV infection. Interestingly, we observed that ATMUV infection could trigger duck innate immune response including robust expression of particular type I and type III IFNs and IFITM family proteins. Our previous studies had shown that ATMUV infection effectively triggers the host innate immune response, including robust upregulation of type I and type III IFNs and some critical ISGs in chicken and CEF (Chen et al., 2016a) . To confirm these findings, DF-1 cell lines expressing specific shRNA targeting each of these IFITMs were infected with ATMUV and harvested at 36 hpi, followed by qRT-PCR assay to detect mRNA expression of viral genes. cache = ./cache/cord-353957-0pjg25kn.txt txt = ./txt/cord-353957-0pjg25kn.txt === reduce.pl bib === id = cord-341478-bicg5ozr author = Aurisicchio, L title = Regulated and prolonged expression of mIFNα in immunocompetent mice mediated by a helper-dependent adenovirus vector date = 2002-01-30 pages = extension = .txt mime = text/plain words = 5934 sentences = 296 flesch = 53 summary = To explore the regulated transgene expression in the context of a helper-dependent vector, we constructed the HD-TET-IFN vector, containing the mIFNα gene under the control of the tetracycline inducible transactivator rtTA2(s)-S2. In addition, C57/B6 mice injected at low HD-TET-IFN doses resulted in Doxmediated regulation of liver restricted mIFN␣ expression, which was associated with induction of antiviral genes. These results indicate that HD-TET-IFN allowed a significant expression of mIFN␣ controlled in vitro by Dox. To verify the efficiency and persistence of mIFN␣ secretion, C57/B6 mice were injected i.v. with 1.4 × 10 10 pp of HD-IFN or HD-TET-IFN and the mIFN␣ released in the serum was measured over time. C57/B6 and Balb/C mice were i.v. injected with different doses of HD-TET-IFN and mIFN␣ measured at day 21 p.i. after a treatment for 3 days with Dox, 200 g/ml, present in the drinking water (Figure 7a ). cache = ./cache/cord-341478-bicg5ozr.txt txt = ./txt/cord-341478-bicg5ozr.txt === reduce.pl bib === id = cord-339991-k8z6v2vx author = Rong, Q. title = Multiple mechanisms for HSV-1 induction of interferon α production by peripheral blood mononuclear cells date = 2003 pages = extension = .txt mime = text/plain words = 5571 sentences = 273 flesch = 48 summary = UV-inactivated, infectious, and other forms of herpes simplex virus 1 (HSV-1) induced interferon (IFN) production by different routes in myeloid origin mononuclear cells (MOMC) (consisting predominantly of monocytes). Comparison of the activities of different strains of infectious HSV, UV-inactivated HSV, and a mutant HSV incapable of penetration (K T) [9] and results of treatment with a mannose receptor antagonist indicate that there are more than one mechanism for HSV induction of interferon in the MOMC origin cell populations. The greater response to UV-inactivated virus suggests that non-infectious virions and possibly HSV infected cell debris are the more potent activators of IFN α production and that replicating virus can limit the induction of interferon production as a means of escaping host protection. Interferons and the colony-stimulating factors IL-3 and GM-CSF enhance the ifn-alpha response in human blood leucocytes induced by herpes simplex virus cache = ./cache/cord-339991-k8z6v2vx.txt txt = ./txt/cord-339991-k8z6v2vx.txt === reduce.pl bib === id = cord-344093-3bniy5b5 author = Peteranderl, Christin title = The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond date = 2017-03-22 pages = extension = .txt mime = text/plain words = 12546 sentences = 578 flesch = 34 summary = A prominent regulator of disease outcome, especially in-but not limited to-respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. (73) Cell death induction, e.g., Bcl-2-associated X protein, caspase-8, Fas-associated protein with death domain, Fas ligand, and TNF-related apoptosis-inducing ligand (TRAIL) dsRNA, polyI:C (4, 110) IAV (4, 5, 10, 115) Sendai virus (110) TRAIL Virus control by apoptosis induction in infected cells IAV (6, 170, 171) Tissue injury by apoptosis of both infected and non-infected alveolar epithelial cells, lung macrophages IAV (5, 7, 10) RSV (137) Necrosis of fibroblasts, dendritic cells, and epithelial cells IAV (146, 147, 168) Increased cellular infiltration CoV (175) Decreased expression of Na,K-ATPase, impaired epithelial fluid reabsorption IAV (11) iNTRODUCTiON In 1957, Isaacs and Lindenmann (1) first recognized the potential of a soluble and probably cell-derived factor to combat influenza virus infection and named this factor interferon [(IFN) from latin interferre, to interfere]. cache = ./cache/cord-344093-3bniy5b5.txt txt = ./txt/cord-344093-3bniy5b5.txt === reduce.pl bib === id = cord-348684-xbxwpmxq author = Liu, Bao-qin title = Ubiquitination modification: critical regulation of IRF family stability and activity date = 2020-10-30 pages = extension = .txt mime = text/plain words = 5231 sentences = 258 flesch = 32 summary = Interferon regulatory factors (IRFs) play pivotal and critical roles in innate and adaptive immune responses; thus, precise and stringent regulation of the stability and activation of IRFs in physiological processes is necessary. Knowledge of how these proteins function and interact with IRFs may provide a better understanding of the regulation of IRFs in immune responses or other biological processes and exciting targets for the development of drugs aimed at regulating the functions of specific E3 ligases or DUBs. Ubiquitination is a type of reversible cellular protein PTM. Furthermore, K63-linked polyubiquitination and monoubiquitination, the second most common type of ubiquitin linkage, mediate proteasome-independent effects, which play an important role in activating many components of different signaling pathways and participate in many biological processes (Ning et al., 2011) . c-Cbl, a member of the Cbl (Casitas B-lineage lymphoma) family, negatively regulates IRF3 protein stability by interacting with the C-terminal domain of IRF3 via its TKB (tyrosine kinase binding) domain and promotes K48-linked polyubiquitination-dependent proteasomal degradation of IRF3 (Zhao et al., 2016) . cache = ./cache/cord-348684-xbxwpmxq.txt txt = ./txt/cord-348684-xbxwpmxq.txt === reduce.pl bib === id = cord-342063-1si0qrrx author = Battesti, G. title = Negative tests for SARS‐CoV‐2 infection do not rule out its responsibility for chilblains date = 2020-08-13 pages = extension = .txt mime = text/plain words = 512 sentences = 39 flesch = 56 summary = They reported 311 patients with acral lesions occurring during the COVID‐19 lockdown in France. They concluded that there is no evidence of SARS‐CoV‐2 infection in the large majority of patients with acral lesions. They reported 311 patients with acral lesions occurring during the COVID-19 lockdown in France. They concluded that there is no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions. They hypothesized that the situation could be due to the media stating that chilblains were caused by SARS-CoV-2 infection and leading to a higher rate of consultation or the lockdown leading to more inactivity and long periods at home barefoot on a cold floor 1 . Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on PCR and serology testing cache = ./cache/cord-342063-1si0qrrx.txt txt = ./txt/cord-342063-1si0qrrx.txt === reduce.pl bib === id = cord-353062-c6luoo3m author = Lauber, C title = Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells date = 2015-09-01 pages = extension = .txt mime = text/plain words = 5449 sentences = 311 flesch = 55 summary = To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. 23 In order to determine whether IFNλ4 can induce an alternative set of genes, that are not induced in the classical IFN response, we have compared the transcriptional response after IFNα, IFNλ3 and IFNλ4 stimulation in both primary human hepatocytes (PHH) and primary human airway epithelial (HAE) cells using transcriptome sequencing (RNA-seq). Compared with a recently published microarray analysis of type I and type III IFN responses in PHH, which used similar statistical thresholds but substantially higher IFNλ concentrations than our study (1000 ng ml − 1 ), 11 our RNA-seq data provide a more complete estimate of the IFN response (87 versus 50 genes significantly regulated by IFNλ3). cache = ./cache/cord-353062-c6luoo3m.txt txt = ./txt/cord-353062-c6luoo3m.txt === reduce.pl bib === id = cord-348993-8r4fhzlm author = Tomosada, Yohsuke title = Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection date = 2013-08-15 pages = extension = .txt mime = text/plain words = 7965 sentences = 432 flesch = 49 summary = CONCLUSIONS: The present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Considering this background, the aims of this study were: a) to investigate whether the nasal administration of Lr05 or Lr06 are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to evaluate whether viability of Lr05 or Lr05 is indispensable to modulate respiratory immunity considering that it was reported that heat-killed lactobacilli strains are able to improve lung defenses [11, 15, 16] and; c) to conclusively demonstrate the protective effect of Lr05 and Lr06 by evaluating their capacity to improve the resistance of infant mice against RSV challenge. cache = ./cache/cord-348993-8r4fhzlm.txt txt = ./txt/cord-348993-8r4fhzlm.txt === reduce.pl bib === id = cord-353337-o302vxqm author = Visser, Linda J. title = Dissecting distinct proteolytic activities of FMDV L(pro) implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression date = 2020-07-15 pages = extension = .txt mime = text/plain words = 9547 sentences = 514 flesch = 54 summary = To study the effects of L pro on the induction of type I IFN in picornavirus-infected cells, we used two previously generated recombinant viruses; EMCV-L Zn , which contains inactivating mutations in the zinc-finger domain of the Leader (i.e. EMCV's RLR signaling antagonist) [1, 43, 44] , and EMCV-L pro , which was derived from EMCV-L Zn and additionally encodes FMDV L pro at the N-terminus of its polyprotein ( Fig 1A) [45]. Cleavage of RLR signaling proteins by FMDV L pro correlates with type I IFN suppression degradation of NF-κB p65 and DUB activity as well as to impair L pro 's ability to reduce IFN-β mRNA expression [36, 39] , also affected L pro 's ability to cleave MAVS and TBK1. Notably, infection with EMCV L pro L143A, which displayed wt deISGylase/DUB activity but is strongly impaired in its ability to cleave/degrade RLR signaling proteins MAVS, TBK1 and NFκB p65, failed to suppress the induction of IFN-β mRNA. cache = ./cache/cord-353337-o302vxqm.txt txt = ./txt/cord-353337-o302vxqm.txt === reduce.pl bib === id = cord-346836-6jyv0q5e author = Ikegami, Tetsuro title = The Pathogenesis of Rift Valley Fever date = 2011-05-06 pages = extension = .txt mime = text/plain words = 10419 sentences = 483 flesch = 46 summary = RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis. RVFV infection in humans primarily causes a self-limiting febrile illness; however, some patients develop hemorrhagic fever, neurological disorders, or blindness after the febrile period [5, 7, 8] . Inbred rat strains mimic the disparate human response to rift valley fever virus infection Clinical, virological and serological response of the west african dwarf sheep to experimental infection with different strains of rift valley fever virus cache = ./cache/cord-346836-6jyv0q5e.txt txt = ./txt/cord-346836-6jyv0q5e.txt === reduce.pl bib === id = cord-343963-99rd3o79 author = Wong, Mun-Teng title = Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection date = 2014-12-29 pages = extension = .txt mime = text/plain words = 17253 sentences = 1074 flesch = 42 summary = 13, 14 Upon infection by viruses such as HCV, viral RNA is first sensed by cellular pattern recognition receptors (PRRs), and the PRR-mediated recruitment of adaptor proteins and the activation of downstream signaling lead to IFN production. First, we briefly discuss the signaling triggered by the retinoic acid-inducible gene 1-like receptor (RLR) and the Toll-like receptor (TLR), which leads to type I IFN synthesis and IFN-mediated signaling pathway activation, resulting in the expression of a variety of effector ISGs. We also summarize the strategies that HCV uses to escape IFN antiviral surveillance. 156 demonstrated that HCVinduced SG formation is IFN-and PKR-dependent and is inversely correlated with the induction of ISG proteins, such as myxovirus resistance gene A (MxA) and Ub-like (UBL)specific protease 18 (USP18), in HCV-infected cells without affecting the mRNA levels of these ISGs. Furthermore, the SG proteins TIA-1, TIAR and G3BP1 have been shown to play a critical role in HCV replication and infectious virus production. cache = ./cache/cord-343963-99rd3o79.txt txt = ./txt/cord-343963-99rd3o79.txt === reduce.pl bib === id = cord-345854-f0dq94j1 author = Chong, Wai Po title = The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome date = 2006-05-04 pages = extension = .txt mime = text/plain words = 1770 sentences = 116 flesch = 54 summary = We examined whether polymorphisms of IFN-γ,TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). In this study, we hypothesized that the polymorphisms of the cytokine genes, i.e. IFN-γ +874A/T, TNF-α -308G/A, IL-10 -1082G/A and -592A/C, might be associated with SARS. We tested our hypotheses in 476 SARS patients and 449 healthy controls and found that polymorphism of IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner. The frequencies of genotypes and alleles of the 4 single nucleotide polymorphisms (SNPs) were compared between the SARS patients and healthy controls by 3 × 2 and 2 × 2 chi square test respectively. Our case-control study genotyped the 4 SNPs IFN-γ +874A/T, TNF-α -308G/A, IL-10 -1082G/A and -592A/C in 476 Chinese patients with SARS and 449 healthy controls. Association between mannose-binding lectin gene polymorphisms and susceptibility to severe acute respiratory syndrome coronavirus infection cache = ./cache/cord-345854-f0dq94j1.txt txt = ./txt/cord-345854-f0dq94j1.txt === reduce.pl bib === id = cord-342800-62jklwiy author = Xu, Shuqin title = mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection date = 2020-09-09 pages = extension = .txt mime = text/plain words = 13579 sentences = 706 flesch = 43 summary = The RNActive ® vaccine platform designed by CureVac used co-delivered RNA and protamine complex as the adjuvant to induce Th1 T cell responses, and naked, unmodified, and sequence-optimized mRNA as the antigen to develop mRNA vaccines [54] . used LNP to deliver self-amplified RNA vaccines, which caused the mRNA expression level in mice to be significantly higher than that of naked mRNA, CD4 + , and CD8 + T cell immune responses were also effectively induced. Overall development steps of those vaccines are (1) constructing the core antigen-encoding mRNA sequence optimized or combined based on selected antigen(s) from the target pathogen; (2) trying and choosing a proper combination of mRNA construction type, adjuvants, carrier materials and the route of administration; (3) detecting in vivo expression of the encoded antigen and the level of elicited immune responses; (4) providing research and demonstrations of immune induction mechanisms. cache = ./cache/cord-342800-62jklwiy.txt txt = ./txt/cord-342800-62jklwiy.txt === reduce.pl bib === id = cord-347225-gh51ag2x author = Fu, Weihui title = A clinical pilot study on the safety and efficacy of aerosol inhalation treatment of IFN-κ plus TFF2 in patients with moderate COVID-19 date = 2020-07-29 pages = extension = .txt mime = text/plain words = 4921 sentences = 233 flesch = 46 summary = INTERPRETATION: Aerosol inhalation of IFN-κ plus TFF2 is a safe treatment and is likely to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby achieves an early release from hospitalization. Therefore, to evaluate the efficacy and safety of intranasal inhalation of TFF2 and IFN-k protein for SARS-CoV-2 infection, we conducted an open-label, nonrandomized, clinical trial in adult patients hospitalized with moderate COVID-19 disease in China. In this trial, any AE from the beginning of aerosol inhalation to 5 days after the end of the last aerosol inhalation were taken as an adverse event during treatment (TEAE); The secondary objective of the pilot study was to evaluate the clinical efficacy of IFN-k plus TFF2 as compared to the control group as assessed by days of hospitalization staying, CT imaging improvement and cough relief time and negative reversion of viral RNA after 10 days of treatment. cache = ./cache/cord-347225-gh51ag2x.txt txt = ./txt/cord-347225-gh51ag2x.txt === reduce.pl bib === id = cord-337458-dc90ecfe author = Markwalter, Christine F. title = Inorganic Complexes and Metal-Based Nanomaterials for Infectious Disease Diagnostics date = 2018-12-04 pages = extension = .txt mime = text/plain words = 40568 sentences = 2391 flesch = 40 summary = In this review, we define the components of a diagnostic to include: (1) the target biomarker, an endogenous indicator of a disease state, which is most often a pathogen or host protein, carbohydrate, or nucleic acid sequence, (2) sample preparation, which allows for biomarker isolation, purification, and/or concentration from complex biological matrices, (3) molecular recognition elements, which specifically capture and detect the target biomarker, (4) signal generation and amplification, and (5) instrumentation for signal read-out. 113, 114 In subsequent studies, the group developed and optimized a hand-held, easy-to-use device 85, 115 (Figure 8A ) in which HRP2-bound, IMAC-functionalized magnetic beads were directly transferred to the sample pad of commercial malaria lateral flow assays. If combined with one of the sample preparation strategies discussed previously (section 3) or integrated with paper or another field-ready substrate, this Ir(III)-based detection strategy could produce a robust and sensitive assay that is applicable in low-resource diagnostic settings. cache = ./cache/cord-337458-dc90ecfe.txt txt = ./txt/cord-337458-dc90ecfe.txt === reduce.pl bib === id = cord-347946-i6kx3n6m author = Raison, Charles L title = Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance date = 2016-09-15 pages = extension = .txt mime = text/plain words = 18693 sentences = 670 flesch = 31 summary = Like sickness behavior, depression in response to immune activation aided in host defense both directly (ie, raised body temperature and energy conservation behaviors) and indirectly (social avoidance, energy conservation, and hypervigilance; Raison and Miller, pathogenhost defense theory of depression [PATHOS-D]) Adaptive explanations for associations between MDD and altered immune functioning are not considered (frequent unexamined assumption of researchers working on proximal mechanisms) Toll-like receptor (TLR) mRNA and protein have been reported to be elevated in both the periphery and CNS of individuals with MDD (Hung et al, 2014 (Hung et al, , 2015 Keri et al, 2014; van Dooren et al, 2016) , with some evidence suggesting that successful pharmaco-or psychotherapy reduces peripheral TLR activity (Keri et al, 2014; Hung et al, 2015) . cache = ./cache/cord-347946-i6kx3n6m.txt txt = ./txt/cord-347946-i6kx3n6m.txt === reduce.pl bib === id = cord-354730-hfau2odb author = Wang, Rong title = Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus date = 2014-07-03 pages = extension = .txt mime = text/plain words = 4923 sentences = 312 flesch = 45 summary = PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. This review summarizes the recent advances in the research of PRRSV interference with IFN-mediated innate immunity, the viral proteins involved, and their molecular mechanisms, as well as diverse effects by different strains and in different cell types. These transcription activation factors translocate into the nucleus and result in induction of type I IFNs and expression of inflammatory cytokines, which not only lead to an antiviral state of the neighboring uninfected cells, but also serve as key regulators to evoke adaptive immune response. Porcine reproductive and respiratory syndrome virus nonstructural protein 1 modulates host innate immune response by antagonizing IRF3 activation Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear translocation cache = ./cache/cord-354730-hfau2odb.txt txt = ./txt/cord-354730-hfau2odb.txt === reduce.pl bib === id = cord-347200-dtwhd6zy author = Ivanova, Daria title = NK Cells in Mucosal Defense against Infection date = 2014-08-14 pages = extension = .txt mime = text/plain words = 6955 sentences = 369 flesch = 49 summary = Mucosal NK cells play a pivotal role in early protection through their cytolytic function and IFNγ production against bacteria, fungi, viruses, and parasitic infections. Since NK precursors and other ILC populations in secondary lymphoid tissues express varying levels of this integrin, it may be possible that an NK-DC interaction is a requirement for immature NK cells to be signaled to home to mucosal sites. During mucosal infections of humans and mice, NK cells are recruited to sites of infection and play an important role in immune defense [6, 48] . Therefore the cytokine milieu present in the different mucosal tissues in addition to activating signals stimulated that by diverse pathogens help NK cells respond to infection. NK cells in humans are also important for innate control of gut mucosal infections. During infection, resident mucosal tissue NK cells respond primarily through IFN production, which contributes directly to early control of pathogens. cache = ./cache/cord-347200-dtwhd6zy.txt txt = ./txt/cord-347200-dtwhd6zy.txt === reduce.pl bib === id = cord-347298-7kqrl3rv author = Hedger, M.P. title = Immunology of the Testis and Male Reproductive Tract date = 2010-07-12 pages = extension = .txt mime = text/plain words = 21168 sentences = 1000 flesch = 46 summary = Thus, it appears unlikely that a lack of APCs is a contributing factor in testicular immune privilege, although differences in the number and distribution of MHC class II-expressing cells in the interstitial tissue of different species or strains may help to explain differences in susceptibility to autoimmune orchitis (Flickinger et al. Moreover, while inhibition of Leydig cell steroidogenesis during inflammation may involve indirect effects at the level of the pituitary, or the actions of inflammatory mediators produced by the testicular macrophages and Sertoli cells, there is evidence that these cells can also respond directly to TLR ligands (Bhushan et al. Activation of p38/Jnk is implicated in the stimulation of proliferation by immature Sertoli cells and the regulation of blood-testis barrier dynamics, steroidogenesis, and multiple inflammatory responses, including the production of IL6, iNOS, monocyte chemoattractant protein 1, and leukocyte adhesion molecules, in the mature Sertoli cell (De Cesaris et al. cache = ./cache/cord-347298-7kqrl3rv.txt txt = ./txt/cord-347298-7kqrl3rv.txt === reduce.pl bib === id = cord-354762-3a3a3ku9 author = Afsar, Cigdem Usul title = SARS-CoV-2 (COVID-19): INTERFERON-EPSILON MAY BE RESPONSIBLE OF DECREASED MORTALITY IN FEMALES date = 2020-06-02 pages = extension = .txt mime = text/plain words = 987 sentences = 70 flesch = 54 summary = title: SARS-CoV-2 (COVID-19): INTERFERON-EPSILON MAY BE RESPONSIBLE OF DECREASED MORTALITY IN FEMALES IFN is particularly expressed in epithelial cells and it is essential in skin and mucosal immunity (lung, intestines and reproductive tissues) of all African and Asian pangolin species (Choo and others, 2016) . IFN, like the other type I IFNs, might be responsible of decreased mortality in females because of its antiviral effects. The JAK/STAT pathway responds to type I IFN secreted from neighboring cells and SARS-CoV proteins have been shown to affect this pathway before (Frieman and Baric, 2008) . JAK-STAT signal blocking by baricitinib (a selective JAK1 and JAK2 inhibitor) produces an impairment of IFN-mediated antiviral response, with a potential facilitating effect on the evolution of SARS-CoV-2 infection. Interferon-epsilon protects the female reproductive tract from viral and bacterial infection cache = ./cache/cord-354762-3a3a3ku9.txt txt = ./txt/cord-354762-3a3a3ku9.txt === reduce.pl bib === id = cord-351489-tzmev77c author = Yuan, Shuofeng title = Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) date = 2020-06-10 pages = extension = .txt mime = text/plain words = 5002 sentences = 238 flesch = 40 summary = They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. In this primary screening, chloroquine, lopinavir, and remdesivir which were recently reported to have anti-SARS-CoV-2 activity, exhibited about 1.3-2.0 log10 copies/mL reduction in viral RNA load ( Figure 1 ). In comparison, recombinant IFN-β demonstrated the most potent anti-SARS-CoV-2 activity, with Avonex (IFN-β1a), Rebif (IFN-β1a), and Betaferon (IFN-β1b) each achieving about 3 log10 copies/mL reduction in viral load. In our primary screening using a fixed antiviral agent concentration and virus inoculum, we identified recombinant IFNs and lipogenesis modulators to be the most potent anti-SARS-CoV-2 agents among 22 broad-spectrum antivirals. cache = ./cache/cord-351489-tzmev77c.txt txt = ./txt/cord-351489-tzmev77c.txt === reduce.pl bib === === reduce.pl bib === id = cord-347460-9vechh4x author = Chang, Feng-Yee title = Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) date = 2020-06-04 pages = extension = .txt mime = text/plain words = 8050 sentences = 384 flesch = 43 summary = Three components are crucial for SARS-CoV induced diseases: 1) the role of CD8+ T cells in defense against the virus, which causes apoptosis in the infected cells, 2) interactions of the virus with macrophages and dendritic cells, which initiate the early innate and subsequent adaptive immune responses, and 3) type I interferon (IFN) system, an innate response against viral infections, which can inhibit virus replication in the early phase. Existing information suggests that the SARS-CoV-infected airways and alveolar epithelial cells secrete abundant chemokines to attract immune cell infiltrations to the lungs, including macrophages and neutrophils, thereby causing damage due to high levels of proinflammatory cytokines and other mediators secreted by these cell types. After a decade of research on coronavirus, unfortunately, still there are no licensed vaccines, effective specific antivirals, nor drug combinations supported by high-level evidence to treat the infection, especially for newly emerging strains such as SARS-COV-2 [59] . cache = ./cache/cord-347460-9vechh4x.txt txt = ./txt/cord-347460-9vechh4x.txt === reduce.pl bib === id = cord-351845-bli3qm8w author = Prasad, Kartikay title = Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective date = 2020-06-26 pages = extension = .txt mime = text/plain words = 4626 sentences = 293 flesch = 46 summary = Towards this goal, in this study, we have generated a human-SARS-CoV-2 interactome based on recently published RNA-Seq analysis of human adenocarcinomic alveolar basal epithelial (A549) cells infected with SARS-CoV-2, and identified disease-related functional genes that will provide the insights into the patho-J o u r n a l P r e -p r o o f 4 mechanisms of COVID-19. Overall, the analysis demonstrated that the upregulated genes are mainly linked to the host response to SARS-CoV-2 infection, type I interferon signaling and the cytokine-mediated signaling pathway. The PPI network analysis indicates that the pathways are enriched in host response to virus infection, type I interferons signaling, and cytokine activation. [74] reported high SARS-CoV-2 loads very early during infection, suggesting that the virus may have developed arsenals that is able to delay the IFN response by inhibiting innate immune signaling. cache = ./cache/cord-351845-bli3qm8w.txt txt = ./txt/cord-351845-bli3qm8w.txt === reduce.pl bib === id = cord-355839-o0m71kvw author = Sedeyn, Koen title = Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses date = 2019-10-17 pages = extension = .txt mime = text/plain words = 8187 sentences = 414 flesch = 45 summary = ATF2, activating transcription factor 2; CDS, cytoplasmic DNA sensor; ER, endoplasmic reticulum; IFN, interferon; IKK, inhibitor of nuclear factor kappa-B kinase; IKKε, inhibitor of nuclear factor kappa-B kinase subunit epsilon; IRF3, interferon regulatory factor 3; IRF7, interferon regulatory factor 7; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MAVS, mitochondrial antiviral-signaling protein; MDA5, melanoma differentiation-associated protein 5; MyD88, myeloid differentiation primary response protein MyD88; NF-kB, nuclear factor-kappa B; NOD2, nucleotide-binding oligomerization domain-containing protein 2; PAMP, pathogenassociated molecular pattern; PRR, pattern recognition receptor; RIG, retinoic-acid-inducible gene-I; RLR, RIG-I-like receptor; RSV, respiratory syncytial virus; STING, stimulator of interferon protein; TBK1, tank binding kinase 1; TICAM1, toll/interleukin-1 receptor domain-containing adapter molecule 1; TIRAP, toll/ interleukin-1 receptor domain-containing adapter protein; TLR, toll-like receptor; TRAF3, tumor necrosis factor receptor-associated factor 3; TRAF6, tumor necrosis factor receptor-associated factor 6; TRAM, toll-like receptor adaptor molecule. cache = ./cache/cord-355839-o0m71kvw.txt txt = ./txt/cord-355839-o0m71kvw.txt === reduce.pl bib === id = cord-356094-sbtigcfr author = Chen, Huijie title = Antiviral Activity Against Infectious Bronchitis Virus and Bioactive Components of Hypericum perforatum L. date = 2019-10-29 pages = extension = .txt mime = text/plain words = 8921 sentences = 485 flesch = 55 summary = perforatum was ethyl acetate extraction section (HPE), and results showed that treatment with HPE significantly reduced the relative messenger ribonucleic acid (mRNA) expression and virus titer of IBV, and reduced positive green immunofluorescence signal of IBV in chicken embryo kidney (CEK) cells. The results of adaptation and replication in CEK cells, such as CPE, reverse transcription polymerase chain reaction (RT-PCR), and IBV growth curve determined by tissue culture infective dose (TCID 50 ) at different time were tested. The relative mRNA expression level of IBV-N gene was detected by qRT-PCR and the virus titer of IBV was determined by TCID 50 to analyze the antiviral effect of HPE, HPW and SEE (Figure 3) . FIgUre 8 | The effects of Hypericum perforatum ethyl acetate (HPE) on infectious bronchitis virus (IBV) messenger ribonucleic acid (mRNA) expression levels of trachea (A) and kidney (B). cache = ./cache/cord-356094-sbtigcfr.txt txt = ./txt/cord-356094-sbtigcfr.txt === reduce.pl bib === id = cord-349647-cfjrwt44 author = Girkin, Jason title = Chapter 8 In vivo experimental models of infection and disease date = 2019-12-31 pages = extension = .txt mime = text/plain words = 12472 sentences = 659 flesch = 35 summary = However, the recognition that RV infection is associated with more severe clinical manifestations in people with chronic lung diseases such as asthma and COPD provided a new impetus to research and a new direction to human experimental infection studies. 166 These studies extend the use of RV infection in mice to new areas, including mechanisms of early life infection susceptibility, to mechanisms of secondary bacterial infection/compromised antimicrobial immunity and experimental exploration of clinical risk factors associated with increased likelihood to develop virus-induced exacerbations of respiratory diseases. 190 In the same elastase-induced model, fluticasone proprionate treatment reduced IFN responses, increased viral load, suppressed airway immune cell numbers (lymphocytes and neutrophils), suppressed inflammatory cytokines (IL-6, TNFα), and increased mucus production, following RV-A1 exacerbation. Human experimental RV challenge studies have shed light on the biology of RV infection and the mechanisms associated with RV-induced exacerbations of chronic respiratory diseases. cache = ./cache/cord-349647-cfjrwt44.txt txt = ./txt/cord-349647-cfjrwt44.txt === reduce.pl bib === id = cord-355671-t890eixt author = Medina, Gisselle N. title = Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo date = 2020-06-16 pages = extension = .txt mime = text/plain words = 6363 sentences = 346 flesch = 46 summary = FMDV Lpro is a papain-like protease (PLP) known to block the cellular innate immune response, at both the transcriptional and translational level by utilizing different mechanisms, including (i) shutting down translation of host capped mRNAs through the cleavage of the translation initiation factor eIF4G (5, 6); (ii) downregulating IFN mRNA expression by causing degradation of NF-B, IRF-3, IRF-7, and LGP2 (7-10); (iii) targeting the chromatin remodeling machinery to disrupt the expression of IFN and ISG mRNAs (11) ; and (iv) targeting of G3BP1/2 to block stress granule formation (12) . Importantly, engineering of an infectious clone carrying this mutation (LproW105A) rendered a viable FMDV with a perceptible level of attenuation and reduced deISGylation and DUB activity compared with wild-type (WT) virus during infection of porcine cells. To confirm these results using the FMDV host-specific ISGylation machinery during infection, we cloned the porcine ISG15 in a replicationdefective human adenovirus type 5 (Ad5) vector (Fig. 5B) and examined its antiviral activity in swine cells. cache = ./cache/cord-355671-t890eixt.txt txt = ./txt/cord-355671-t890eixt.txt === reduce.pl bib === id = cord-351520-c5fi2uoh author = Zhong, Bo title = Regulation of virus-triggered type I interferon signaling by cellular and viral proteins date = 2010-02-01 pages = extension = .txt mime = text/plain words = 10571 sentences = 637 flesch = 46 summary = Recently, we and others identified a new adapter protein called mediator of IRF3 activation (MITA, also known as STING), which plays a critical role in virus-induced type I IFN expression (Ishikawa and Barber, 2008; Zhong et al., 2008) . cache = ./cache/cord-351520-c5fi2uoh.txt txt = ./txt/cord-351520-c5fi2uoh.txt === reduce.pl bib === id = cord-351532-2yd4wg9v author = Huang, Yin-Qiu title = No Statistically Apparent Difference in Antiviral Effectiveness Observed Among Ribavirin Plus Interferon-Alpha, Lopinavir/Ritonavir Plus Interferon-Alpha, and Ribavirin Plus Lopinavir/Ritonavir Plus Interferon-Alpha in Patients With Mild to Moderate Coronavirus Disease 2019: Results of a Randomized, Open-Labeled Prospective Study date = 2020-07-14 pages = extension = .txt mime = text/plain words = 5739 sentences = 260 flesch = 48 summary = title: No Statistically Apparent Difference in Antiviral Effectiveness Observed Among Ribavirin Plus Interferon-Alpha, Lopinavir/Ritonavir Plus Interferon-Alpha, and Ribavirin Plus Lopinavir/Ritonavir Plus Interferon-Alpha in Patients With Mild to Moderate Coronavirus Disease 2019: Results of a Randomized, Open-Labeled Prospective Study The proportion of patients with SARS-CoV-2 nucleic acid negativity in the LPV/r+IFN-α-treated group (61.1%) was higher than the RBV+ IFN-α-treated group (51.5%) and the RBV+LPV/r+IFN-α-treated group (46.9%) at day 14; however, the difference between these groups was calculated to be statistically insignificant. The office of National Health Commission of the People's Republic of China, and the National Administration Bureau of Traditional Chinese Medicine have jointly issued different versions of the "Guidelines for diagnosis and treatment of novel coronavirus pneumonia", in which LPV/r, IFNa, and RBV are recommended for on-trial use in patients with COVID-19. cache = ./cache/cord-351532-2yd4wg9v.txt txt = ./txt/cord-351532-2yd4wg9v.txt === reduce.pl bib === id = cord-354620-xf6glr2h author = Tian, Bin title = Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus date = 2020-01-28 pages = extension = .txt mime = text/plain words = 8895 sentences = 373 flesch = 48 summary = Our study provided practical methods for isolating and culturing duck primary cells, and our results will facilitate further investigations of organ tropism, innate immune responses, latent infection, and the effectiveness of antiviral drugs for treating DPV and potentially other aerial bird pathogens. In the present study, we isolated five types of duck primary cells [duck embryo fibroblasts (DEFs), neurons, astrocytes, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages] to identify appropriate cell models for DPV, using tropism infection and innate immunologic assays. Upon stimulation with DNA viruses, monocytes/macrophages exhibit higher levels of IFN-β, ISG, and inflammatory cytokine expression than DEFs, neurons, astrocytes, and PBMCs. To elucidate the mechanisms associated with the different responses of the five types of duck primary cells to DNA and RNA virus analogs, the basal levels of innate immune factors were compared. cache = ./cache/cord-354620-xf6glr2h.txt txt = ./txt/cord-354620-xf6glr2h.txt === reduce.pl bib === id = cord-353826-owoec2ud author = Graham, Simon P. title = Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date = 2020-07-27 pages = extension = .txt mime = text/plain words = 5496 sentences = 269 flesch = 53 summary = Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Analysis of SARS-CoV-2 S proteinspecific murine splenocyte responses by IFN-γ ELISpot assay showed no statistically significant difference between the primeonly and prime-boost vaccination regimens, in either strain of mouse (Fig. 1a) . SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 prime-only and prime-boost vaccination regimens in mice and pigs SARS-CoV-2 S protein-specific antibody titres in serum were determined by ELISA using recombinant soluble trimeric S (FL-S) and receptor binding domain (RBD) proteins. Small animal models have variable success in predicting vaccine efficacy in larger animals but are an important To analyse SARS-CoV-2 S-specific T cell responses, all mice were sacrificed on day 49 for isolation of splenocytes and pigs were blood sampled longitudinally to isolate PBMC. cache = ./cache/cord-353826-owoec2ud.txt txt = ./txt/cord-353826-owoec2ud.txt === reduce.pl bib === id = cord-356197-js7l86fh author = Zhou, Ping title = Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo date = 2011-08-07 pages = extension = .txt mime = text/plain words = 4640 sentences = 219 flesch = 40 summary = Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Genome-wide transcriptional responses of lungs of Landrace×Yorkshire crossbred piglets to a classical North American type PRRSV strain infection was analyzed by Solexa/Illumina's Digital Gene Expression (DGE) System, which is a tag-based high-throughput transcriptome sequencing method [6] . This systematic analysis of the pulmonary gene expression profiles suggested that upregulation expression of pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during PRRSV infection processes [6] . Microarray analysis revealed that HP-PRRSV infection has affected PAMs in vivo in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. cache = ./cache/cord-356197-js7l86fh.txt txt = ./txt/cord-356197-js7l86fh.txt === reduce.pl bib === id = cord-354000-jxqskt4k author = Warren, Cody J. title = The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date = 2014-05-14 pages = extension = .txt mime = text/plain words = 4420 sentences = 265 flesch = 47 summary = Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. IFITM protein expression induced by type I IFN inhibits infection of many RNA viruses [22] [23] [24] [25] [26] [27] [28] [29] [30] . Therefore, we analyzed induction of IFITM1, 2 and 3 expression by IFN-b treatment in human keratinocytes, the natural host cells for HPV. To determine the effect of IFITMs on HPV16 entry, HeLa cells stably expressing c-Myc-tagged IFITM1, 2 or 3 or with vector alone ( Fig. 2A-B) were infected with HPV16-LucF. Using various epithelial cell lines and primary keratinocytes expressing IFITMs, we show that HPV infection is surprisingly enhanced by IFITM1 and IFITM3 overexpression (Fig. 2) . Taken together, our results suggest that HPV and other DNA viruses may have evolved to avoid IFITM1, 2 and 3 restriction during entry into host cells. cache = ./cache/cord-354000-jxqskt4k.txt txt = ./txt/cord-354000-jxqskt4k.txt ===== Reducing email addresses cord-004400-li1sc47z cord-022631-s4n24xij cord-023375-x4p187u7 cord-023388-btbf6wkg cord-023387-tyeh14wz cord-023391-bq5w3jk9 cord-023390-5hcgdlmt cord-023372-ft8cp9op cord-023373-6wh1kb3p cord-023374-87ob1exq cord-023394-ptfjxpo6 cord-023392-axd0901z cord-023403-jzdrvfvr cord-023402-8qfmo6rq cord-023417-by18aczt cord-023389-ilrp8vb7 cord-023393-8nye3nc8 cord-023414-xxw5kptr cord-023415-hhvmsn5b cord-023410-eblcf902 cord-023430-5zuewjv2 cord-023438-g0k0vvdc cord-023441-q83y12sk cord-023431-zjyrhlxn cord-023425-3sjsogvq cord-023443-pvz7dll9 cord-023407-s85g7g0x cord-023419-lnmc6vv5 cord-023445-c4tqioz1 cord-023433-d1b7qvhs cord-015147-h0o0yqv8 cord-023429-x52gbklw cord-023411-iszb5qlk cord-023439-r04y1j22 cord-034467-jh9msz1c 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cord-022888-dnsdg04n cord-015021-pol2qm74 cord-009567-osstpum6 cord-022888-dnsdg04n cord-265005-e6rpryrh cord-288960-v6l6o5va number of items: 445 sum of words: 3,218,537 average size in words: 11,413 average readability score: 47 nouns: cells; virus; cell; patients; infection; expression; response; protein; mice; type; responses; levels; treatment; activation; study; results; production; disease; activity; interferon; role; gene; proteins; replication; viruses; host; infections; data; studies; genes; receptor; group; factor; induction; analysis; blood; control; effect; system; cytokine; cytokines; effects; immunity; antibody; macrophages; time; influenza; liver; pathway; function verbs: inducing; using; shown; increasing; associated; compared; infected; include; signaling; mediated; bind; found; activated; inhibited; suggest; demonstrated; expressed; following; observed; indicated; treating; reducing; identified; detected; involving; produced; result; led; determined; stimulated; based; required; cause; regulating; reported; performed; developed; contain; describe; investigate; provided; related; play; revealed; decreased; enhance; presenting; evaluated; derived; targeted adjectives: viral; immune; human; antiviral; specific; respiratory; inflammatory; clinical; anti; innate; high; different; severe; higher; significant; acute; important; cellular; dependent; non; low; chronic; like; positive; several; similar; negative; first; primary; early; infected; normal; lower; major; multiple; dendritic; molecular; present; recombinant; healthy; many; new; epithelial; functional; single; novel; regulatory; bacterial; porcine; various adverbs: also; however; significantly; well; respectively; therefore; previously; recently; highly; furthermore; moreover; directly; even; interestingly; still; together; often; prior; currently; less; alone; especially; double; specifically; thereby; mainly; later; strongly; finally; approximately; additionally; subsequently; first; particularly; now; potentially; rather; similarly; early; yet; indeed; relatively; differentially; rapidly; primarily; fully; generally; much; far; completely pronouns: we; i; it; their; our; its; they; them; he; his; she; her; us; itself; iga1; one; themselves; you; nsp15; your; isgf3; eph-4; ifitm3; ns3/4a; pdcs; me; mrnas; ifnλ4; my; mg; him; stat1; interleukin-15; ifit5; e804; ifnar1; λr1; interleukin-10; ifit1; trim21; nsp10; itims; il-1-β; igg1; esat-6; s; ripks; r348; ours; oneself proper nouns: IFN; RNA; T; SARS; C; Fig; TNF; CD4; NK; CD8; HCV; CoV; þ; MBL; B; I; PCR; IL-12; IL-6; α; IRF3; II; mg; CoV-2; HBV; γ; IL-10; A; MHC; PRRSV; M; mRNA; HLA; AE; DC; COVID-19; β; RSV; L; DNA; LPS; MERS; MS; University; IFN-; TLR; ELISA; HIV-1; IAV; HIV keywords: ifn; cell; rna; sars; tnf; cd8; virus; infection; il-12; mbl; patient; rig; covid-19; hcv; dna; irf3; cd4; prrsv; mhc; pcr; mers; ifn-; result; response; respiratory; protein; cns; stat1; rsv; il-6; viral; type; pedv; mhv; study; sting; pkr; mouse; interferon; hiv-1; hiv; gene; university; tlr3; tbk1; mda5; isg15; iav; hla; hbv one topic; one dimension: cells file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572141/ titles(s): Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression three topics; one dimension: virus; patients; cells file(s): https://www.ncbi.nlm.nih.gov/pubmed/28829373/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712310/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169534/ titles(s): The TRIMendous Role of TRIMs in Virus–Host Interactions | Poster Exhibition | Pneumococcal IgA1 Protease Activity Interferes with Opsonophagocytosis of Streptococcus Pneumoniae Mediated by Serotype‐Specific Human Monoclonal IgA1 Antibodies five topics; three dimensions: virus ifn cells; cells cell il; patients il cells; ifn cells virus; patients treatment liver file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053439/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169490/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086569/, https://www.ncbi.nlm.nih.gov/pubmed/28829373/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712310/ titles(s): Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence | Lysine‐Dependent Binding of OspE to the C‐terminus of Factor H Mediates Complement Resistance in Borrelia burgdorferi | 2019 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference | The TRIMendous Role of TRIMs in Virus–Host Interactions | Poster Exhibition Type: cord title: keyword-ifn-cord date: 2021-05-25 time: 00:34 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:ifn ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-008821-rxzgfk1k author: A. Lucchiari, Maria title: In vivo depletion of interferon-gamma leads to susceptibility of A/J mice to mouse hepatitis virus 3 infection date: 2011-11-02 words: 2416.0 sentences: 97.0 pages: flesch: 45.0 cache: ./cache/cord-008821-rxzgfk1k.txt txt: ./txt/cord-008821-rxzgfk1k.txt summary: Abbreviations; MHV3 = mouse hepatitis virus 3; IFN = interferon; Fes = fetal calf serum; PFU = plaque-forming units; ip = intraperitoneally; Ab = antibodies; PBS = phosphate buffer solution against our strain of MHV3 is acquired after immunization and the mechanism involved is dependent on the IFN -y synthesis and the macrophage sensitivity to IFN-y (9). Although, in view of the crucial regulatory function of CD4 cells and the important role of CDS cells as cytotoxic effector cells during a virusspecific immune response, the results cannot unequivocally exclude the interpretation that susceptibility of the immunosuppressed animals may be due to the absence of proper immune effector mechanisms, the lack of clearance of the virus in the peritoneum and liver of AI] treated and infected mice (Figure 1) , which leads to high rates of mortality (Table 1) , may be attributed to the lack of IFN-y in the serum or peritoneal exudate of them (Fig. 3) , which has been shown in vitro to be effective to restrict the MHV3 growth in target cells such as macrophages (6, 7, 9) . abstract: The possible role of interferon-gamma (IFN-γ) in the resistance of A/J mice to MHV3 infection was investigated. Monoclonal antibodies specific for IFN-γ, CD4 and CD8 molecules were administered in vivo to deplete selectively the IFN-y synthesized or the appropriate subset of T cells. The animals were then infected with MHV3 and the course of infection was followed by studying different parameters, such as, the mortality, the virus growth in the tissues and the IFN-γ synthesis in sera and peritoneal exudates. After MHV3 infection, a full resistance of control A/J mice was observed, in contrast to the high mortality rate observed among the depleted animals, where higher virus titers were found in different tissues. The IFN-γ synthesis in sera and peritoneal exudates of depleted mice, after MHV3 infection, drastically decreased when compared to that detected in control mice. The data presented are consistent with the hypothesis that IFN-γ plays an essential role in the resistance of A/J mice to MHV3 infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134495/ doi: 10.1016/s0171-2985(11)80089-6 id: cord-278397-u33x4jaw author: Abe, Takayuki title: Negative Regulation of Cytosolic Sensing of DNA date: 2018-10-29 words: 7194.0 sentences: 377.0 pages: flesch: 41.0 cache: ./cache/cord-278397-u33x4jaw.txt txt: ./txt/cord-278397-u33x4jaw.txt summary: Recent efforts have focused on identifying relevant immune surveillance sensors and components of downstream signaling-Toll-like receptors (TLRs) and their cognate ligands, cytosolic sensing of RNA (primary mediated by the RIG-I/IPS-1 axis), cytosolic sensing of DNA (primary mediated by the cGAS/STING axis), and the inflammasome pathway (primary mediated by NOD-like receptors; NLRs) (Broz and Monack, 2013; Kieser and Kagan, 2017; Kumar et al., 2011a ). It has also been suggested that chronic cGAS/STING activation induced by self DNA may be responsible for induction of aberrant inflammatory diseases like systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and polyarthritis (Barber, 2015; Crowl et al., 2017) . Use of DNA damage induced agents like 7,12-dimethylbenz-α-anthracene (DMBA) has helped shed light on the underlying events initiate the DNA damage-induced immune response via cytosolic DNA sensing pathway and implicates nucleosome leakage in eliciting cGAS/STING-dependent signal activation via recognition of self-DNA (Barber, 2015) . abstract: In mammals, cytosolic detection of nucleic acids is critical in initiating innate antiviral responses against invading pathogens (like bacteria, viruses, fungi and parasites). These programs are mediated by multiple cytosolic and endosomal sensors and adaptor molecules (c-GAS/STING axis and TLR9/MyD88 axis, respectively) and lead to the production of type I interferons (IFNs), pro-inflammatory cytokines, and chemokines. While the identity and role of multiple pattern recognition receptors (PRRs) have been elucidated, such immune surveillance systems must be tightly regulated to limit collateral damage and prevent aberrant responses to self- and non-self-nucleic acids. In this review, we discuss recent advances in our understanding of how cytosolic sensing of DNA is controlled during inflammatory immune responses. url: https://doi.org/10.1016/bs.ircmb.2018.09.002 doi: 10.1016/bs.ircmb.2018.09.002 id: cord-276350-lcl9jn35 author: Acharya, Dhiraj title: Dysregulation of type I interferon responses in COVID-19 date: 2020-05-26 words: 1608.0 sentences: 83.0 pages: flesch: 40.0 cache: ./cache/cord-276350-lcl9jn35.txt txt: ./txt/cord-276350-lcl9jn35.txt summary: In a mouse model of SARS-CoV infection, local IFN responses in the lungs were delayed relative to peak viral replication, which impeded virus clearance and was associated with the development of CRS 5 . By contrast, IFNAR inhibition enhanced the recruitment of neutrophils to the lungs in MERS-CoV-infected mice, leading to elevated production of pro-inflammatory cytokines 6 . While patients with severe COVID-19 showed profound depletion and functional exhaustion of NK cells 8 , it is unclear whether this NK cell dysfunction is due to dysregulation of IFN responses. It is thus tempting to speculate that the deficient or dysregulated IFN responses elicited by SARS-CoV-2 infection may influence the generation of T reg cells during the recovery phase of COVID-19. Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice abstract: Infection with SARS-CoV-2 can lead to excessive production of pro-inflammatory cytokines, but the production of type I interferons, which are key antiviral mediators, is reportedly blunted. Here, we discuss how imbalanced interferon responses may contribute to the pathology of COVID-19. url: https://doi.org/10.1038/s41577-020-0346-x doi: 10.1038/s41577-020-0346-x id: cord-354762-3a3a3ku9 author: Afsar, Cigdem Usul title: SARS-CoV-2 (COVID-19): INTERFERON-EPSILON MAY BE RESPONSIBLE OF DECREASED MORTALITY IN FEMALES date: 2020-06-02 words: 987.0 sentences: 70.0 pages: flesch: 54.0 cache: ./cache/cord-354762-3a3a3ku9.txt txt: ./txt/cord-354762-3a3a3ku9.txt summary: title: SARS-CoV-2 (COVID-19): INTERFERON-EPSILON MAY BE RESPONSIBLE OF DECREASED MORTALITY IN FEMALES IFN is particularly expressed in epithelial cells and it is essential in skin and mucosal immunity (lung, intestines and reproductive tissues) of all African and Asian pangolin species (Choo and others, 2016) . IFN, like the other type I IFNs, might be responsible of decreased mortality in females because of its antiviral effects. The JAK/STAT pathway responds to type I IFN secreted from neighboring cells and SARS-CoV proteins have been shown to affect this pathway before (Frieman and Baric, 2008) . JAK-STAT signal blocking by baricitinib (a selective JAK1 and JAK2 inhibitor) produces an impairment of IFN-mediated antiviral response, with a potential facilitating effect on the evolution of SARS-CoV-2 infection. Interferon-epsilon protects the female reproductive tract from viral and bacterial infection abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32521376/ doi: 10.1016/j.jri.2020.103154 id: cord-023403-jzdrvfvr author: Ahlfors, E. title: Proliferation of Cells in the Oral Mucosa, the Ear Skin and the Regional Lymph Nodes in Mice Sensitized and Elicited with a Hapten date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: During contact sensitivity reaction, immune cells proliferate. In order to study the histological picture of these proliferation phases, we used a mouse model of contact sensitivity in the oral mucosa and on skin. We also used bromodeoxyuridin (BrdU, an analogue to thymidin) that is incorporated into the nucleus during cell replication. The hapten oxazolone (OXA) was used to sensitize and elicit the oral mucosa and/or the ear skin. Mice were killed at various times after elicitation, and unsensitized animals were also exposed to the hapten as controls. BrdU (25 mg/kg animal) was injected i.p. 2 h before the kill. Specimens from the oral mucosa, ear skin and submandibular and auricular lymph nodes were cut and fixed in 4% paraformaldehyde. They were then treated with acid and biotinylated anti‐BrdU antibody and developed using ABC‐kit and DAB. The analyses were performed using a Leica light microscope and the computer program analysis. In the oral mucosa, the frequency of proliferating cells were increasing during the observation period, 4–24 h after elicitation, regardless of site of sensitization. The proliferating cells were found mainly in the basal cell layer of the epithelium. Similar patterns were found in ear skin. The regional lymph nodes demonstrated a few scattered proliferating cells 4 h after elicitation. After 24 h, these cells were found frequently in the whole lymph node. Control animals exhibited considerable less proliferating cells at all times. We conclude that most proliferating cells were found 24 h after elicitation locally at the hapten‐exposed sites (the oral mucosa or the ear skin) as well as in the regional lymph nodes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169538/ doi: 10.1111/j.0300-9475.2004.01423ac.x id: cord-272695-wmzq4lkh author: Ahmed, Ahmed A. title: TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis date: 2020-05-13 words: 3813.0 sentences: 210.0 pages: flesch: 55.0 cache: ./cache/cord-272695-wmzq4lkh.txt txt: ./txt/cord-272695-wmzq4lkh.txt summary: This study was undertaken to test the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. The amplified PCR product for TNF-α-308 was detected at 184 base pair as shown in Fig. 1 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls (supplementary file (Table 3 ). The amplified PCR product for IFN-γ + 874 were detected at 263 base pair as shown in Fig. 2 , based on these results, different species of CL, the genotypes and the alleles of the host genes polymorphism were determined and evaluated in comparison with their respective healthy controls. abstract: BACKGROUND: Cutaneous leishmaniasis (CL) is well linked with immunogenetic factors. This study was undertaken to test the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. METHODS: This is a case-control study involved 169 Saudi subjects with different L. species and 199 healthy controls from central region of Saudi Arabia. All subjects were characterized by TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms using PCR. RESULTS: Evaluation of genotyping and allelic frequency of TNF-α − 308 G/A in different L. species showed no significant association compared to controls (p > 0.05). Except, in cases of L. tropica that showed significantly higher TNF-α − 308 A versus G allele frequency (p = 0.0004). Evaluation of genotyping of IFN-γ + 874 (TT versus AA+AT recessive) and allelic frequency of IFN-γ + 874 (T versus A) showed significant higher in L. major and also in total CL cases as compared to healthy controls (p < 0.05). Furthermore, a strong association was observed between the susceptibility of L. major, L. tropica or total CL cases with synergistically combined high TNF-α 308/INF-γ 874 alleles. CONCLUSIONS: This is the first report that shows the gene polymorphisms of TNF-α − 308 G/A and IFN-γ + 874 A/T in Saudi patients with different L. species infections. Data showed that the TNF-α-308 G/A gene polymorphism is not associated with the susceptibility of CL in Saudi subjects. The only correlation was found in between A versus G allelic frequency in L. tropica. Importantly, IFN-γ + 874 A/T polymorphism was found to be associated with the susceptibility of L. major and also with total CL subjects. Moreover, data from synergistically combined high TNF-α 308/INF-γ 874 alleles strongly suggest their potential role in the susceptibility of leishmania infection. url: https://www.ncbi.nlm.nih.gov/pubmed/32404058/ doi: 10.1186/s12881-020-01043-9 id: cord-262673-j2ot35lt author: Ahmed-Hassan, Hanaa title: Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections date: 2020-08-18 words: 8591.0 sentences: 472.0 pages: flesch: 41.0 cache: ./cache/cord-262673-j2ot35lt.txt txt: ./txt/cord-262673-j2ot35lt.txt summary: Furthermore, respiratory epithelial cells and lung macrophages are capable of secreting a broad range of chemokines like IL-8, Macrophage inflammatory protein-1 (MIP-1), RANTES and cytokines including TNF-α, IL-6, IL-1β that influence the types of immune cells being recruited to the area in response to acute viral infections (177, 178) . Both Influenza and SARS virus can induce acute lung injury (ALI) which is accompanied by high levels of C5a, leading to the influx and activation of innate immune cells (199) (Figure 1) . Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus Middle East respiratory syndrome coronavirus shows poor replication but significant induction of antiviral responses in human monocytederived macrophages and dendritic cells Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells abstract: The new pandemic virus SARS-CoV-2 emerged in China and spread around the world in <3 months, infecting millions of people, and causing countries to shut down public life and businesses. Nearly all nations were unprepared for this pandemic with healthcare systems stretched to their limits due to the lack of an effective vaccine and treatment. Infection with SARS-CoV-2 can lead to Coronavirus disease 2019 (COVID-19). COVID-19 is respiratory disease that can result in a cytokine storm with stark differences in morbidity and mortality between younger and older patient populations. Details regarding mechanisms of viral entry via the respiratory system and immune system correlates of protection or pathogenesis have not been fully elucidated. Here, we provide an overview of the innate immune responses in the lung to the coronaviruses MERS-CoV, SARS-CoV, and SARS-CoV-2. This review provides insight into key innate immune mechanisms that will aid in the development of therapeutics and preventive vaccines for SARS-CoV-2 infection. url: https://doi.org/10.3389/fimmu.2020.01979 doi: 10.3389/fimmu.2020.01979 id: cord-294125-v2dr4hm0 author: Albert, Manuel title: ISG15, a Small Molecule with Huge Implications: Regulation of Mitochondrial Homeostasis date: 2018-11-13 words: 8040.0 sentences: 444.0 pages: flesch: 33.0 cache: ./cache/cord-294125-v2dr4hm0.txt txt: ./txt/cord-294125-v2dr4hm0.txt summary: Finally, based on our recent observations, we discuss the essential functions of mitochondria in the antiviral response and examine the role of ISG15 in the regulation of mitochondrial processes, specifically OXPHOS and mitophagy. Binding to IFNARs leads to the activation of the Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT) signaling pathway and the formation of the interferon-stimulated gene factor 3 (ISGF3) complex, with the subsequent expression of IFN-stimulated genes [3] that establish an antiviral state and play important roles in determining the host innate and adaptive immune responses [4] . In the following sections, we discuss the antiviral mechanisms mediated by ISGylation of both viral and cellular proteins, with a focus on mitochondrial proteins, as we recently showed that ISG15 modulates essential mitochondrial metabolic processes such as respiration and mitophagy in macrophages, with important implications for innate immune responses [29] . abstract: Viruses are responsible for the majority of infectious diseases, from the common cold to HIV/AIDS or hemorrhagic fevers, the latter with devastating effects on the human population. Accordingly, the development of efficient antiviral therapies is a major goal and a challenge for the scientific community, as we are still far from understanding the molecular mechanisms that operate after virus infection. Interferon-stimulated gene 15 (ISG15) plays an important antiviral role during viral infection. ISG15 catalyzes a ubiquitin-like post-translational modification termed ISGylation, involving the conjugation of ISG15 molecules to de novo synthesized viral or cellular proteins, which regulates their stability and function. Numerous biomedically relevant viruses are targets of ISG15, as well as proteins involved in antiviral immunity. Beyond their role as cellular powerhouses, mitochondria are multifunctional organelles that act as signaling hubs in antiviral responses. In this review, we give an overview of the biological consequences of ISGylation for virus infection and host defense. We also compare several published proteomic studies to identify and classify potential mitochondrial ISGylation targets. Finally, based on our recent observations, we discuss the essential functions of mitochondria in the antiviral response and examine the role of ISG15 in the regulation of mitochondrial processes, specifically OXPHOS and mitophagy. url: https://www.ncbi.nlm.nih.gov/pubmed/30428561/ doi: 10.3390/v10110629 id: cord-023375-x4p187u7 author: Alitalo, A. title: Lysine‐Dependent Binding of OspE to the C‐terminus of Factor H Mediates Complement Resistance in Borrelia burgdorferi date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Serum resistance of Borrelia burgdorferi strains belonging to the B. afzelii and B. burgdorferi sensu stricto genospecies is dependent on binding of complement inhibitor factor H. We recently reported that factor H binding by B. burgdorferi is due to inducible expression of several approximately 20 kDa plasmid‐encoded, surface‐exposed lipoproteins related to OspE (e.g. ErpA, ErpP and P21). In addition, a second class of factor H‐binding proteins of approximately 27–35 kDa has been described. The OspE‐related lipoproteins are dramatically induced by B. burgdorferi during transmission from its tick vector into the mammalian host. The induction of OspE‐related lipoproteins during mammalian infection may play a key a role in the borrelial evasion of the host's immune system. The goal of the present study was to define the factor H‐binding regions of OspE‐related proteins using mutagenesis, peptide mapping and surface plasmon resonance analysis (Biacore). The combined studies revealed that the C‐terminal regions of both human and mouse factor H (SCRs 18–20) specifically bind to OspE‐related lipoproteins. We also found FHR‐1, whose C‐terminal SCRs 3–5 are homologous to SCRs 18–20 of factor H, to bind to OspE. Peptide mapping revealed five putative regions (designated I‐V) in OspE that could directly interact with factor H. Deleting the C‐terminal 15 amino acid residues from region V of P21 abolished its ability to bind factor H. At the same time, however, synthetic peptides corresponding to the C‐termini of OspE, P21 and ErpP did not inhibit factor H binding to OspE. Thus, the C‐terminal‐binding region V appears to be necessary but not sufficient for factor H binding. When a more specific mutation strategy was employed, where single amino acid residues in peptides spanning over the factor H‐binding regions were mutated to alanines, we observed that lysines in the factor H‐binding regions of OspE were required for factor H binding. The combined data have revealed that key lysine residues in OspE‐related lipoproteins and ionic interactions are crucial for factor H interactions. Furthermore, binding of OspE to the C‐termini of both mouse and human factor H suggests that Borrelia spirochetes utilize analogous complement resistance mechanisms in both rodents and man. In Borrelia garinii strains, which in in vitro analyses have been found to be sensitive to complement killing, differences in the OspE sequences as well as in the expression of factor H‐binding proteins may account for their susceptibility to serum lysis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169490/ doi: 10.1111/j.0300-9475.2004.01423aj.x id: cord-271114-hv3gwvdi author: Allam, Gamal title: Neonatal infections in Saudi Arabia: Association with cytokine gene polymorphisms date: 2015-04-22 words: 5564.0 sentences: 313.0 pages: flesch: 52.0 cache: ./cache/cord-271114-hv3gwvdi.txt txt: ./txt/cord-271114-hv3gwvdi.txt summary: The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. Therefore, the primary aim of the current study was to investigate SNPs in the IL-1β -31 T/C (rs1143643), IL-6 -174 G/C (rs1800795), TNF-α -308 G/A (rs1800629), and IFN-γ +874 A/T (rs2430561) genes for their possible association with susceptibility to EOS in Saudi newborn infants. Newborns with sepsis had significantly higher serum levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) compared to both suspected and sepsis-free control groups (overall p value < 0.001, Table 1 ). abstract: In recent years, many studies have reported potential associations between cytokine gene polymorphisms and the development, course, and outcome of sepsis, often with apparently conflicting results. The objective of this study was to investigate single nucleotide polymorphism (SNP) in the interleukin (IL)-1β –31 T/C, IL-6 –174 G/C, tumor necrosis factor α (TNF-α) –308 G/A, and interferon γ (IFN-γ) +874 A/T genes for their possible association with susceptibility to early onset sepsis (EOS) in Saudi newborn infants. A total of 205 newborn infants aged 1-2 days were consecutively enrolled onto the study having met the inclusion criteria (as per the research protocol). DNA was extracted from filter papers using the Chelex-100 method. The cytokines SNP were genotyping using Taqman 5’ nuclease allelic discrimination. For cytokine measurements we used the commercially available Enzyme-Linked Immunosorbent Assay (ELISA) kit. Our results show that the circulating IL-1β, IL-6, TNF-α, and IFN-γ were significantly (p < 0.001) elevated in EOS patients compared to suspected and sepsis-free control groups; and IL-1β –31C, IL-6 –174G, TNF-α –308G, and IFN-γ +874A alleles were associated with EOS in Saudi infants. In conclusion, analysis of cytokines concentrations and SNP for the four tested genes can be used as a predictor of sepsis outcome in newborns. url: https://doi.org/10.5114/ceji.2015.50836 doi: 10.5114/ceji.2015.50836 id: cord-267099-rv6npz8z author: An, Dong title: Molecular characterization and biological activity of bovine interferon-omega3 date: 2017-02-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bovine interferon-omega3 (BoIFN-ω3) gene was amplified from bovine liver genomic DNA, which encodes a 195-amino acid protein containing a 23-amino acid signal peptide. Analysis of the molecular characteristics revealed that BoIFN-ω3 evolving from IFN-ω, contained four cysteine residues and five alpha helices, showing that BoIFN-ω3 presented the typical molecular characteristics of type I interferon. BoIFN-ω3 exhibited antiviral and antiproliferative activities, which exerted a protective effect against VSV in several mammalian cell lines, as well as against BEV, IBRV, and BVDV in MDBK cell. Moreover, BoIFN-ω3 was shown to be highly sensitive to trypsin, but remaining stable despite changes in pH and temperature. Additionally, BoIFN-ω3 induced the transcription of Mx1, ISG15, and ISG56 genes, as well as the expression of Mx1 protein in a time-dependent manner. These findings will be useful to further study BoIFN-ω in host's defence against infectious diseases, particularly viral infections. Furthermore, results will facilitate further research on the bovine interferon family. url: https://www.sciencedirect.com/science/article/pii/S0034528816301667 doi: 10.1016/j.rvsc.2017.01.028 id: cord-253501-hkxlq3os author: Anang, Saumya title: Recent Advances Towards the Development of a Potent Antiviral Against the Hepatitis E Virus date: 2018-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. It also causes acute liver failure and acute-on-chronic liver failure in many patients, such as those suffering from other infections/liver injuries or organ transplant/chemotherapy recipients. Despite widespread sporadic and epidemic incidents, there is no specific treatment against HEV, justifying an urgent need for developing a potent antiviral against it. This review summarizes the known antiviral candidates and provides an overview of the potential targets for the development of specific antivirals against HEV. url: https://doi.org/10.14218/jcth.2018.00005 doi: 10.14218/jcth.2018.00005 id: cord-321992-lk2ao6m8 author: Annamalai, Thavamathi title: Age-dependent variation in innate immune responses to porcine epidemic diarrhea virus infection in suckling versus weaned pigs date: 2015-12-15 words: 8539.0 sentences: 472.0 pages: flesch: 58.0 cache: ./cache/cord-321992-lk2ao6m8.txt txt: ./txt/cord-321992-lk2ao6m8.txt summary: In the present study, we investigated the innate immune responses such as cytokine and NK cell activity as well as changes in frequencies of T cells to examine if differences coincide with the higher disease severity of suckling versus weaned pigs. The infected weaned pigs also had significantly higher NK cell frequencies in blood and ileum at PID 5 (P < 0.05) compared to infected suckling pigs ( Fig. 2A and B) . In infected suckling and weaned groups, peak IFN␣, IL-12 and TNF␣ levels coincided with onset of diarrhea and fecal PEDV RNA shedding and peak serum PEDV RNA titers (PIDs 1 and 3, respectively); and (4) Frequencies of CD3+CD4+ T cells were significantly higher in ileum of suckling pigs than in weaned pigs, whereas there was no difference in frequency of CD3+CD8+ T cells. abstract: Porcine epidemic diarrhea (PED) is an enteric coronaviral infection that causes severe morbidity and mortality in suckling pigs, but less severe disease in older pigs. Consequently, it causes significant economic losses to the pork industry. There are limited studies on the innate immune responses to PED virus (PEDV) in pigs. The aims of our study were to investigate differences in innate immune responses to PEDV infection in suckling and weaned pigs and to examine if disease severity coincides with reduced innate immune responses. Weaned 26-day-old pigs (n = 20) and 9-day-old nursing pigs (n = 20) were assigned to PEDV inoculated or uninoculated control groups. The pigs were observed daily for clinical signs, virus shedding and were euthanized at post-inoculation days (PIDs) 1 and 5 to assay immune responses. Blood samples were collected at PIDs 1, 3 and 5. The natural killer (NK) cell frequencies, NK cell activities (lysis of target K562 tumor cells in vitro), CD3+CD4+ T cell and CD3+CD8+ T cell frequencies were measured in blood and ileum at PIDs 1 and 5. The PEDV infected suckling pigs showed severe diarrhea and vomiting at PID 1, whereas the PEDV infected weaned pigs showed milder clinical signs starting at PID 3. PEDV infected suckling pigs had significantly higher diarrhea scores, earlier fecal PEDV RNA shedding and significantly higher viremia (viral RNA in serum) compared to weaned pigs. There was no mortality in either infected suckling or infected weaned pigs. The control pigs not inoculated with PEDV did not show any clinical signs and no detectable fecal or serum PEDV RNA. Strikingly, PEDV infected suckling pigs had significantly lower NK cell frequencies, undetectable NK cell activity and lower IFNγ producing NK cells in blood and ileum compared to PEDV infected weaned pigs. Pro-inflammatory cytokine profiles of PEDV infected suckling pigs differed from those of PEDV infected weaned pigs and coincided with onset of fecal PEDV RNA shedding and serum PEDV RNA titers. The infected suckling pigs have higher and earlier increases in serum IFNα, but lower serum IL-8 and TNFα levels compared to infected weaned pigs. CD3+CD4+ T cell frequencies were significantly higher in ileum of suckling pigs than in weaned pigs, whereas there was no difference in CD3+CD8+ T cell frequencies. In conclusion, the observations of impaired lytic activity and IFN-γ production by NK cells in suckling pigs coincided with the increased severity of PEDV infection in the suckling pigs compared with the weaned pigs. url: https://www.sciencedirect.com/science/article/pii/S0165242715002032 doi: 10.1016/j.vetimm.2015.09.006 id: cord-003514-yyzbv7ys author: Arslan, Mehboob title: Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken date: 2019-02-14 words: 6080.0 sentences: 326.0 pages: flesch: 44.0 cache: ./cache/cord-003514-yyzbv7ys.txt txt: ./txt/cord-003514-yyzbv7ys.txt summary: The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Although CEF do not possess receptors for IFN-λ, slight temporal expression of DEGs in response to chIFN-λ treatment signifies its antiviral potential in primary cells. Furthermore, studies have also revealed that a high degree of cell type specificity in receptor-ligand interactions make avian IFNs distinct from mammalian IFNs. Recently, it has been established that chicken IFN-λ inhibits low pathogenic influenza virus replication in CEFs; however, as compared to chIFN-γ and chIFN-β, higher doses are required to induce ISGs and maintain the strong antiviral state in the cells [14] . Our data suggest that significant antiviral, cell cycle regulators, and biologically active genes are expressed in response to administered chicken IFN. abstract: Interferons (IFNs) are pleiotropic cytokines that establish a first line of defense against viral infections in vertebrates. Several types of IFN have been identified; however, limited information is available in poultry, especially using live animal experimental models. IFN-lambda (IFN-λ) has recently been shown to exert a significant antiviral impact against viral pathogens in mammals. In order to investigate the in vivo potential of chicken IFN-λ (chIFN-λ) as a regulator of innate immunity, and potential antiviral therapeutics, we profiled the transcriptome of chIFN-λ-stimulated chicken immune organs (in vivo) and compared it with primary chicken embryo fibroblasts (in vitro). Employing the baculovirus expression vector system (BEVS), recombinant chIFN-λ3 (rchIFN-λ3) was produced and its biological activities were demonstrated. The rchIFNλ3 induced a great array of IFN-regulated genes in primary chicken fibroblast cells. The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Interestingly, this experimental approach revealed contrasting evidence of the antiviral potential of chIFN-λ in both in vivo and in vitro models. Taken together, our data signifies the potential of chIFN-λ as a potent antiviral cytokine and highlights its future possible use as an antiviral therapeutic in poultry. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409627/ doi: 10.3390/genes10020145 id: cord-023411-iszb5qlk author: Astrinidou‐Vakaloudi, A. title: Presence of Helicobacter pylori Antibodies in Haemodialysis Patients date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Aim: Renal dysfunction may influence the colonization of gastric mucosa by urea‐splitting bacteria such as Helicobacter pylori, by increasing urea concentrations in the gastric juice. Our aim was to investigate the prevalence of H. pylori in patients with end‐stage renal disease (ESRD), receiving long‐term haemodialysis treatment. Methods: This study included 40 sera from patients with ESRD (29 male and 11 female) undergoing periodic haemodialysis; mean time of treatment was 42.6 months. Using ELISA technique, we investigated the presence of IgG and IgA antibodies against H. pylori as well as IgG CagA (antibodies specific for CagA(+) strains of H. pylori). Sera from 40 healthy blood donors were used as a control group. Results: H. pylori IgG antibodies were detected in 32 out of 40 (80%) patients in the dialysis group, while 31/40 (77.5%) tested positive for IgA. IgG CagA antibodies were present in 13 out of 40 (32.5%). Prevalence of H. pylori IgG, IgA and CagA IgG antibodies in the control group was 33, 7 and 15%, respectively. Conclusions: Although international data suggest that prevalence of H. pylori infection is the same in ESRD patients as in healthy individuals, in our study that seems not to be the case. The higher blood and gastric juice urea levels may be a risk factor (among many others), but more studies are required in order to understand the relation of H. pylori infection in this group of patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169550/ doi: 10.1111/j.0300-9475.2004.01423p.x id: cord-341478-bicg5ozr author: Aurisicchio, L title: Regulated and prolonged expression of mIFNα in immunocompetent mice mediated by a helper-dependent adenovirus vector date: 2002-01-30 words: 5934.0 sentences: 296.0 pages: flesch: 53.0 cache: ./cache/cord-341478-bicg5ozr.txt txt: ./txt/cord-341478-bicg5ozr.txt summary: To explore the regulated transgene expression in the context of a helper-dependent vector, we constructed the HD-TET-IFN vector, containing the mIFNα gene under the control of the tetracycline inducible transactivator rtTA2(s)-S2. In addition, C57/B6 mice injected at low HD-TET-IFN doses resulted in Doxmediated regulation of liver restricted mIFN␣ expression, which was associated with induction of antiviral genes. These results indicate that HD-TET-IFN allowed a significant expression of mIFN␣ controlled in vitro by Dox. To verify the efficiency and persistence of mIFN␣ secretion, C57/B6 mice were injected i.v. with 1.4 × 10 10 pp of HD-IFN or HD-TET-IFN and the mIFN␣ released in the serum was measured over time. C57/B6 and Balb/C mice were i.v. injected with different doses of HD-TET-IFN and mIFN␣ measured at day 21 p.i. after a treatment for 3 days with Dox, 200 g/ml, present in the drinking water (Figure 7a ). abstract: A major goal in gene therapy is to develop efficient gene transfer protocols that allow tissue-specific, long-term and tightly regulated expression of the desired transgene. This objective is becoming more attainable through the co-evolution of gene transfer vectors and regulation systems. The ideal vector should efficiently transduce non-dividing cells with minimal toxicity, thus endowing the system with persistent transgene expression. The helper-dependent adenovirus vectors meet these requirements, as demonstrated in various studies in the literature. The most promising regulation system is the tet-on system, which has low basal transcriptional activity and high inducibility. To explore the regulated transgene expression in the context of a helper-dependent vector, we constructed the HD-TET-IFN vector, containing the mIFNα gene under the control of the tetracycline inducible transactivator rtTA2(s)-S2. Mice injected with HD-TET-IFN showed high levels of serum mIFNα only upon transcriptional activation. The transgene expression was reinducible to the same high level up to 3 months p.i., and the amount of expressed cytokine could be regulated by dosing doxycycline. Transcriptional activation of mIFNα induced by doxycycline resulted in prolonged survival and reduced liver damage in HD-TET-IFN-injected mice challenged with a lethal dose of coronavirus. Activation of antiviral genes mediated by doxycycline-dependent mIFNα expression was also observed at low HD-TET-IFN doses. The possibility of controlling gene expression by the combination of HD vectors and the latest tet-on transactivator also holds promise for studying gene function in other animal models. url: https://www.ncbi.nlm.nih.gov/pubmed/11821934/ doi: 10.1038/sj.gt.3301596 id: cord-001546-ndz3oarf author: Ayithan, Natarajan title: Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date: 2015-02-26 words: 5128.0 sentences: 298.0 pages: flesch: 52.0 cache: ./cache/cord-001546-ndz3oarf.txt txt: ./txt/cord-001546-ndz3oarf.txt summary: Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. The aim of this study was to further investigate molecular bases of postexposure protection by VLPs. Based on our previous report that VLPs stimulate type I IFN expression in DCs and macrophages, in vitro, we focused on the role of type I IFN signaling, and found that post-exposure VLP treatment leads to accelerated activation of IFN signaling, resulting in early induction of ISGs. Significantly, VLP stimulated ISG induction coincided with the attenuation of proinflammatory cytokine surge in EBOV infected mice. abstract: Ebola virus (EBOV) causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs) are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar(-/-) mice. Accordingly, EBOV infected Ifnar(-/-) mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342244/ doi: 10.1371/journal.pone.0118345 id: cord-308932-pp8etmwq author: Baker, M. L. title: Antiviral Immune Responses of Bats: A Review date: 2012-08-01 words: 8600.0 sentences: 397.0 pages: flesch: 45.0 cache: ./cache/cord-308932-pp8etmwq.txt txt: ./txt/cord-308932-pp8etmwq.txt summary: Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Consistent with the results obtained from bats immunized with /X174 or SRBC antigens, vaccination and experimental viral infections have provided evidence for quantitative and qualitative differences in antibody responses in bats compared with other mammals. It is evident they have similar antibody and T-cell receptor genes, cytokines and chemokines, transcription factors, cluster of differentiation (CD) markers and activation pathways found in the immune responses of other mammalian species. abstract: Despite being the second most species‐rich and abundant group of mammals, bats are also among the least studied, with a particular paucity of information in the area of bat immunology. Although bats have a long history of association with rabies, the emergence and re‐emergence of a number of viruses from bats that impact human and animal health has resulted in a resurgence of interest in bat immunology. Understanding how bats coexist with viruses in the absence of disease is essential if we are to begin to develop therapeutics to target viruses in humans and susceptible livestock and companion animals. Here, we review the current status of knowledge in the field of bat antiviral immunology including both adaptive and innate mechanisms of immune defence and highlight the need for further investigations in this area. Because data in this field are so limited, our discussion is based on both scientific discoveries and theoretical predictions. It is hoped that by provoking original, speculative or even controversial ideas or theories, this review may stimulate further research in this important field. Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Although bats appear to share most features of the immune system with other mammals, several studies have reported qualitative and quantitative differences in the immune responses of bats. These observations warrant further investigation to determine whether such differences are associated with the asymptomatic nature of viral infections in bats. url: https://www.ncbi.nlm.nih.gov/pubmed/23302292/ doi: 10.1111/j.1863-2378.2012.01528.x id: cord-017785-zwnkrs23 author: Baker, Michelle L. title: Mammalia: Chiroptera: Immunology of Bats date: 2018-03-10 words: 9426.0 sentences: 450.0 pages: flesch: 46.0 cache: ./cache/cord-017785-zwnkrs23.txt txt: ./txt/cord-017785-zwnkrs23.txt summary: The role of bats as natural reservoirs of a variety of high-profile viruses that are highly pathogenic in other susceptible species yet cause no clinical disease in bats has led to a resurgence of interest in their immune systems. RNAseq studies on tissues and cells from a variety of different species of bats have provided evidence that bats have nearly all of the major components of the immune system that are present in other mammals, including receptors and molecules associated with innate and adaptive immunity and microRNAs (Papenfuss et al. Responses to antigens such as ϕX174 bacteriophage and sheep red blood cells have demonstrated that the generation of neutralizing antibodies is delayed in the big brown bat, the pteropid bat, and the Indian flying fox (Pteropus giganteus) (Hatten et al. abstract: Bats are a large and diverse group comprising approximately 20% of all living mammalian species. They are the only mammals capable of powered flight and have many unique characteristics, including long lifespans, echolocation, and hibernation, and play key roles in insect control, pollination, and seed dispersal. The role of bats as natural reservoirs of a variety of high-profile viruses that are highly pathogenic in other susceptible species yet cause no clinical disease in bats has led to a resurgence of interest in their immune systems. Equally compelling is the urgency to understand the immune mechanisms responsible for the susceptibility of bats to the fungus responsible for white syndrome, which threatens to wipe out a number of species of North American bats. In this chapter we review the current knowledge in the field of bat immunology, focusing on recent highlights and the need for further investigations in this area. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122446/ doi: 10.1007/978-3-319-76768-0_23 id: cord-342189-ya05m58o author: Banerjee, Abhik K. title: SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses date: 2020-10-08 words: 11469.0 sentences: 647.0 pages: flesch: 55.0 cache: ./cache/cord-342189-ya05m58o.txt txt: ./txt/cord-342189-ya05m58o.txt summary: Here, we comprehensively define the interactions between each SARS-CoV-2 protein and human RNAs. We show that 10 viral proteins form highly specific interactions with mRNAs or ncRNAs, including those involved in progressive steps of host cell protein production. We show J o u r n a l P r e -p r o o f 5 that NSP16 binds to the mRNA recognition domains of the U1 and U2 RNA components of the spliceosome and acts to suppress global mRNA splicing in SARS-CoV-2-infected human cells. We identified several pathogenic functions of SARS-CoV-2 in human cells -including global inhibition of host mRNA splicing, protein translation, and membrane protein trafficking -and described the molecular mechanisms by which the virus acts to disrupt these essential cell processes. abstract: SARS-CoV-2 is a recently identified coronavirus that causes the respiratory disease known as COVID-19. Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the Signal Recognition Particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses. url: https://api.elsevier.com/content/article/pii/S0092867420313106 doi: 10.1016/j.cell.2020.10.004 id: cord-263433-oldy0gta author: Barriocanal, Marina title: Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin date: 2015-01-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Many long non-coding RNAs (lncRNAs) are expressed in cells but only a few have been well characterized. In these cases, lncRNAs have been shown to be key regulators of several cellular processes. Therefore, there is a great need to understand the function of more lncRNAs and their regulation in response to stimuli. Interferon (IFN) is a key molecule in the cellular antiviral response. IFN binding to its receptor activates transcription of several IFN-stimulated genes (ISGs) that function as potent antivirals. In addition, several ISGs are positive or negative regulators of the IFN pathway. This is essential to ensure a strong antiviral response and a later return of the cell to homeostasis. As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. The results show that IFN-treatment regulates the expression of several unknown non-coding transcripts. We have validated two lncRNAs upregulated after treatment with different doses of type I IFNα2 in different cells or with type III IFNλ. These lncRNAs were also induced by influenza and vesicular stomatitis virus mutants unable to block the IFN response, but not by several wild-type lytic viruses tested. These lncRNA genes were named lncISG15 and lncBST2 as they are located close to ISGs ISG15 and BST2, respectively. Interestingly, inhibition experiments showed that lncBST2 is a positive regulator of BST2. Therefore lncBST2 has been renamed BISPR, from BST2 IFN-stimulated positive regulator. Our results may have therapeutic implications as lncBST2/BISPR, but also lncISG15 and their coding neighbors, are increased in cells infected with hepatitis C virus and in the liver of infected patients. These results allow us to hypothesize that several lncRNAs could be activated by IFN to control the potency of the antiviral IFN response. url: https://www.ncbi.nlm.nih.gov/pubmed/25620967/ doi: 10.3389/fimmu.2014.00655 id: cord-307914-lgprrwee author: Bartok, Eva title: Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids date: 2020-07-14 words: 17726.0 sentences: 1100.0 pages: flesch: 51.0 cache: ./cache/cord-307914-lgprrwee.txt txt: ./txt/cord-307914-lgprrwee.txt summary: Indeed, the functionalization of CRISPR/Cas systems as a tool for genomic editing have revealed important differences in human and murine NA sensing, including distinct cell subset expression patterns of NA-sensing Toll-Like Receptors (TLRs) or species differences in the structural requirements for the detection of cyclic dinucleotide cGAMP by STING. As a long dsRNA with a 5 0 diphosphate terminus, polyI:C is known to activate the sensing receptors TLR3, MDA5, and RIG-I (Alexopoulou et al., 2001; Gitlin et al., 2006; Kato et al., 2008; Yoneyama et al., 2005) , accessory proteins such including LGP2 and members of the DDX and DHX families (reviewed in Oshiumi et al., 2016) as well as the restriction factors PKR and the OAS family (Farrell et al., 1978; Hovanessian et al., 1977; Zilberstein et al., 1978) . abstract: All lifeforms have developed highly sophisticated systems equipped to detect altered self and non-self nucleic acids (NA). In vertebrates, NA-sensing receptors safeguard the integrity of the organism by detecting pathogens, dyshomeostasis and damage, and inducing appropriate responses to eliminate pathogens and reconstitute homeostasis. Effector mechanisms include i) immune signaling, ii) restriction of NA functions such as inhibition of mRNA translation, and iii) cell death pathways. An appropriate effector response is necessary for host defense, but dysregulated NA-sensing can lead to devastating autoimmune and autoinflammatory disease. Their inherent biochemical similarity renders the reliable distinction between self NA under homeostatic conditions and altered or exogenous NA particularly challenging. In this review, we provide an overview of recent progress in our understanding of the closely coordinated and regulated network of innate immune receptors, restriction factors, and nucleases to effectively respond to pathogens and maintain host integrity. url: https://doi.org/10.1016/j.immuni.2020.06.014 doi: 10.1016/j.immuni.2020.06.014 id: cord-342063-1si0qrrx author: Battesti, G. title: Negative tests for SARS‐CoV‐2 infection do not rule out its responsibility for chilblains date: 2020-08-13 words: 512.0 sentences: 39.0 pages: flesch: 56.0 cache: ./cache/cord-342063-1si0qrrx.txt txt: ./txt/cord-342063-1si0qrrx.txt summary: They reported 311 patients with acral lesions occurring during the COVID‐19 lockdown in France. They concluded that there is no evidence of SARS‐CoV‐2 infection in the large majority of patients with acral lesions. They reported 311 patients with acral lesions occurring during the COVID-19 lockdown in France. They concluded that there is no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions. They hypothesized that the situation could be due to the media stating that chilblains were caused by SARS-CoV-2 infection and leading to a higher rate of consultation or the lockdown leading to more inactivity and long periods at home barefoot on a cold floor 1 . Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on PCR and serology testing abstract: We read with great interest the report of Le Cleach et al discussing chilblains as a manifestation of COVID‐19 pandemic. They reported 311 patients with acral lesions occurring during the COVID‐19 lockdown in France. The most frequent clinical presentation of these acral lesions was typical chilblains. Among the 150 patients with RT‐PCR testing and/or serology, only 10 had confirmed COVID‐19. They concluded that there is no evidence of SARS‐CoV‐2 infection in the large majority of patients with acral lesions. They hypothesized that the situation could be due to the media stating that chilblains were caused by SARS‐CoV‐2 infection and leading to a higher rate of consultation or the lockdown leading to more inactivity and long periods at home barefoot on a cold floor(1). url: https://doi.org/10.1111/bjd.19483 doi: 10.1111/bjd.19483 id: cord-302953-gr2kk9w4 author: Baxter, Victoria K. title: Interferon-Gamma Modulation of the Local T Cell Response to Alphavirus Encephalomyelitis date: 2020-01-16 words: 10529.0 sentences: 487.0 pages: flesch: 55.0 cache: ./cache/cord-302953-gr2kk9w4.txt txt: ./txt/cord-302953-gr2kk9w4.txt summary: In Phase 1, during the first 7 to 8 days post infection (DPI), both infectious virus and viral RNA increase rapidly, followed by clearance of infectious virus that occurs primarily through cooperative effects of anti-SINV antibody and the cytokine interferon-gamma (IFN-γ) [6] [7] [8] [9] . Gbp2 ( Figure 2A ) and Irgm ( Figure 2B ), two genes associated with autophagy [25] , were highly expressed by SINV-infected dAP-7 cells treated with IFN-γ, as were Oasl2 ( Figure 2C ), a member of the 2''-5''oligoadenylate/RNaseL system [26] , and Rsad2 ( Figure 2D ), which encodes viperin, a protein that interferes with assembly and release of many viruses [27] . To determine the effects of IFN-γ signaling on immune cell subsets after SINV infection, cells isolated from the CLNs and brains of WT, Ifng −/− and Ifngr1 −/− mice were examined by flow cytometry. To determine the effects of IFN-γ signaling on immune cell subsets after SINV infection, cells isolated from the CLNs and brains of WT, Ifng −/− and Ifngr1 −/− mice were examined by flow cytometry. abstract: Infection of mice with Sindbis virus (SINV) provides a model for examining the role of the immune response to alphavirus infection of the central nervous system (CNS). Interferon-gamma (IFN-γ) is an important component of this response, and we show that SINV-infected differentiated neurons respond to IFN-γ in vitro by induction of antiviral genes and suppression of virus replication. To determine the in vivo effects of IFN-γ on SINV clearance and T cell responses, C57BL/6 mice lacking IFN-γ or IFN-γ receptor-1 were compared to wild-type (WT) mice after intracranial SINV infection. In WT mice, IFN-γ was first produced in the CNS by natural killer cells and then by CD4(+) and CD8(+) T cells. Mice with impaired IFN-γ signaling initiated clearance of viral RNA earlier than WT mice associated with CNS entry of more granzyme B-producing CD8(+) T cells. However, these mice established fewer CD8(+) tissue-resident memory T (T(RM)) cells and were more likely to experience reactivation of viral RNA synthesis late after infection. Therefore, IFN-γ suppresses the local development of granzyme B-expressing CD8(+) T cells and slows viral RNA clearance but promotes CD8(+) T(RM) cell establishment. url: https://doi.org/10.3390/v12010113 doi: 10.3390/v12010113 id: cord-001808-47496o0e author: Bayat, Ahmad title: Anti-cytokine autoantibodies in postherpetic neuralgia date: 2015-10-20 words: 4246.0 sentences: 213.0 pages: flesch: 50.0 cache: ./cache/cord-001808-47496o0e.txt txt: ./txt/cord-001808-47496o0e.txt summary: Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN. High levels of neutralizing anti-IFN-γ autoantibodies were also detected in patients with disseminated nontuberculous mycobacteria and other opportunistic infections, including both with localized and disseminated VZV reactivation [14, 15] . The finding that several patients each harbored single, neutralizing autoantibodies against interferon-α, GM-CSF or IL-6 suggests that anti-cytokine immunodeficiency may contribute to development of PHN. Particularly relevant was the finding of six PHN patients (one against anti-IFN-α, three against IFN-γ, one against GM-CSF, and one against IL-6) with high levels of autoantibodies greater than 100,000 LU that might have potential neutralizing activity against the target (Fig. 1) . abstract: BACKGROUND: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. METHODS: Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens. In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients. Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity. RESULTS: Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6. In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines. Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV. In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-α, GM-CSF or interleukin-6. In contrast, none of the HZ patients without PHN had neutralizing autoantibodies. CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617715/ doi: 10.1186/s12967-015-0695-6 id: cord-275643-lbikoyo3 author: Beidas, Meshal title: Effect of Human Coronavirus OC43 Structural and Accessory Proteins on the Transcriptional Activation of Antiviral Response Elements date: 2018-07-24 words: 3419.0 sentences: 192.0 pages: flesch: 53.0 cache: ./cache/cord-275643-lbikoyo3.txt txt: ./txt/cord-275643-lbikoyo3.txt summary: The expression of antiviral genes involved in the type I IFN and NF-κB signaling pathways was also downregulated in the presence of HCoV-OC43 structural or accessory proteins. CONCLUSION: Both structural and accessory HCoV-OC43 proteins are able to inhibit antiviral response elements in HEK-293 cells, and to block the activation of different antiviral signaling pathways. Following SeV challenge of HEK-293 cells, the expression of genes involved in the type I IFN and NF-κB signaling pathways was downregulated in the presence of HCoV-OC43 structural or accessory proteins (Fig. 4) . Similar to influenza A NS1 protein, HCoV-OC43 structural (M and N) and accessory (ns2a and ns5a) proteins were able to inhibit the transcriptional activity of antiviral response elements, ISRE, IFN-β promoter, and NF-κB-RE, and to downregulate the expression of several genes involved in the activation of an antiviral response. abstract: OBJECTIVES: The molecular mechanisms underlying the pathogenesis of human coronavirus OC43 (HCoV-OC43) infection are poorly understood. In this study, we investigated the ability of HCoV-OC43 to antagonize the transcriptional activation of antiviral response elements. METHODS: HCoV-OC43 structural (membrane M and nucleocapsid N) and accessory proteins (ns2a and ns5a) were expressed individually in human embryonic kidney 293 (HEK-293) cells. The transcriptional activation of antiviral response elements was assessed by measuring the levels of firefly luciferase expressed under the control of interferon (IFN)-stimulated response element (ISRE), IFN-β promoter, or nuclear factor kappa B response element (NF-κB-RE). The antiviral gene expression profile in HEK-293 cells was determined by PCR array. RESULTS: The transcriptional activity of ISRE, IFN-β promoter, and NF-κB-RE was significantly reduced in the presence of HCoV-OC43 ns2a, ns5a, M, or N protein, following the challenge of cells with Sendai virus, IFN-α or tumor necrosis factor-α. The expression of antiviral genes involved in the type I IFN and NF-κB signaling pathways was also downregulated in the presence of HCoV-OC43 structural or accessory proteins. CONCLUSION: Both structural and accessory HCoV-OC43 proteins are able to inhibit antiviral response elements in HEK-293 cells, and to block the activation of different antiviral signaling pathways. url: https://doi.org/10.1159/000490566 doi: 10.1159/000490566 id: cord-255781-55zrmgxq author: Bergman, Scott J. title: Interferons as Therapeutic Agents for Infectious Diseases date: 2011-12-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This article explains the rationale for development of interferons as therapeutic agents, and describes commercial products available today. It also provides a summary of studies that have been performed with interferons for use as exogenous biological response modifiers in viral infections. Overall, the best data exist for treatment of viral hepatitis B and C, for which interferons are a cornerstone of therapy. Although infections with human papillomavirus and common cold viruses sometimes respond favorably to interferons, their outcomes are far from ideal. Finally, the role of interferons as vaccine adjuvants is still being explored but could be promising. url: https://www.sciencedirect.com/science/article/pii/S0891552011000560 doi: 10.1016/j.idc.2011.07.008 id: cord-023390-5hcgdlmt author: Bhuvanath, S. title: Inflammatory Cytokine Modulation of Cancer Cell Proliferation date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Inflammatory cytokines have a critical role in modulation of both innate and adaptive immunity in response to foreign antigen. They also play an important role in anticancer immunity. For example, they can promote cell‐mediated immunity against cancer cells. With their immunostimulatory effects, these cytokines are being tested for cancer treatment in the form of DNA vaccine or adjuvant or therapeutic cytokines. Direct effect of these cytokines on cancer cell, however, is still unclear. In this project, we investigated whether IL‐1( and IL‐18 can modulate cancer cell proliferation. We employed a simple nonradioactive proliferation (MTT) assay and detection of lactate dehydrogenase (LDH) to test the effect of these recombinant human cytokines on various cancer cell lines, including breast cancer cell line (MCF‐7), oral carcinoma cell line (KB), colon cancer cell line (Caco‐2) and choriocarcinoma cell line (Jar). Cytokines used in this study had both inhibitory and stimulatory effect on cell proliferation. Findings in this project could provide an insight of cancer cell response to these cytokines and this could lead to a consideration on using cytokine as immunotherapy for cancer treatment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169513/ doi: 10.1111/j.0300-9475.2004.01423bi.x id: cord-333955-bnzbppof author: Biesold, Susanne E. title: Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum date: 2011-11-30 words: 5016.0 sentences: 275.0 pages: flesch: 51.0 cache: ./cache/cord-333955-bnzbppof.txt txt: ./txt/cord-333955-bnzbppof.txt summary: Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. Cells from Pteropus species have been shown to produce high amounts of interferon (IFN)-l after stimulation with the double-strand (ds)RNA analogue poly IC, and after infection with the bat-associated paramyxovirus, Tioman [13] . In accordance with the IFN mRNA induction, the highest equivalent amount of bioactive secreted IFN upon RVFV 13 virus infection and poly IC transfection was measured in EidNi/41.3 cells, followed by MEF and MA104 (Figure 3 ). Increases of infectious virus formation were about 1000-fold within 24 hpi, and specific infectivities, expressed as PFU per genome equivalent (PCR units), were highly comparable between cell cultures ( Figure 4C) . abstract: Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs. url: https://doi.org/10.1371/journal.pone.0028131 doi: 10.1371/journal.pone.0028131 id: cord-008761-b36x05fn author: Billiau, A. title: The interferon system as a basis for antiviral therapy or prophylaxis date: 2012-02-26 words: 2464.0 sentences: 127.0 pages: flesch: 45.0 cache: ./cache/cord-008761-b36x05fn.txt txt: ./txt/cord-008761-b36x05fn.txt summary: Possessing satisfactory answers to these questions is essential, not only to understand the natural role of the interferon system in virus disease but also to assess possible applications in medicine, in particular the use of interferons or interferoninducing substances as antiviral drugs. Interferon prepared from mouse cell lines infected with Newcastle disease virus is a mixture of a and B (6) . The main difference between these products and their natural-source-derived counterparts is that they contain only a single subtype, namely a2'' While it is known that different subtypes of HuIFN-~ may differ in their antiviral potency depending on the cells on which they are tested, it is not yet known whether this has any repercussion for the clinical effects. Although these side-chains do not playa significant role in the effects of the IFN-S on cells, the pharmacokinetic behavior of this rDd-IFN-S was found to be rather different from that of natural fibroblast-derived interferon (8) . abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134133/ doi: 10.1016/s0166-3542(85)80020-6 id: cord-001236-cgiok0ce author: Binjawadagi, Basavaraj title: An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination date: 2014-03-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating respiratory disease of pigs. The disease is caused by the PRRS virus (PRRSV), an Arterivirus which is a highly mutating RNA virus. Widely used modified live PRRSV vaccines have failed to prevent PRRS outbreaks and reinfections; moreover, safety of the live virus vaccines is questionable. Though poorly immunogenic, inactivated PRRSV vaccine is safe. The PRRSV infects primarily the lung macrophages. Therefore, we attempted to strengthen the immunogenicity of inactivated/killed PRRSV vaccine antigens (KAg), especially in the pig respiratory system, through: 1) entrapping the KAg in biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP-KAg); 2) coupling the NP-KAg with a potent mucosal adjuvant, whole cell lysate of Mycobacterium tuberculosis (M. tb WCL); and 3) delivering the vaccine formulation twice intranasally to growing pigs. We have previously shown that a single dose of NP-KAg partially cleared the challenged heterologous PRRSV. Recently, we reported that NP-KAg coupled with unentrapped M. tb WCL significantly cleared the viremia of challenged heterologous PRRSV. Since PRRSV is primarily a lung disease, our goal in this study was to investigate lung viral load and various immune correlates of protection at the lung mucosal surfaces and its parenchyma in vaccinated heterologous PRRSV-challenged pigs. Our results indicated that out of five different vaccine-adjuvant formulations, the combination of NP-KAg and unentrapped M. tb WCL significantly cleared detectable replicating infective PRRSV with a tenfold reduction in viral RNA load in the lungs, associated with substantially reduced gross and microscopic lung pathology. Immunologically, strong humoral (enhanced virus neutralization titers by high avidity antibodies) and cell-mediated immune responses (augmented population of interferon-γ secreting CD4(+) and CD8(+) lymphocytes and reduced secretion of immunosuppressive cytokines) in the lungs were observed. In conclusion, combination of NP-KAg and soluble M. tb WCL elicits broadly cross-protective anti-PRRSV immunity in the pig respiratory system. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969340/ doi: 10.2147/ijn.s59924 id: cord-270534-ebkwv4zo author: Bodmer, Bianca S. title: Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model date: 2018-06-11 words: 6539.0 sentences: 362.0 pages: flesch: 53.0 cache: ./cache/cord-270534-ebkwv4zo.txt txt: ./txt/cord-270534-ebkwv4zo.txt summary: title: Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model One of these candidates, MV vac2 -MERS-S(H) (Malczyk et al., 2015) , is based on the measles virus (MV) vaccine platform technology (Mühlebach, 2017) , and encodes the MERS-CoV spike protein (S) as an additional antigen in the backbone of recombinant MV vac2 (del Valle et al., 2007) resembling vaccine strain Moraten that is authorized and in use in the US since 1968. (G) Secretion of IFN-γ after antigen-specific re-stimulation of splenocytes harvested 32 days post prime immunization and after co-culture with JAWSII (left) or DC2.4 (middle) dendritic cells transgenic for MERS-N (black) or untransduced controls (NC, white). To assess the capacity of the different MV vac2 -MERS-S(H) vaccine preparations to induce MERS-CoV S-specific cellular immune responses, splenocytes of mice, which had already been tested for humoral responses ( Fig. 2A) , were isolated and analyzed 49 days after immunization for antigen(Ag)-dependent IFN-γ secretion using ELISpot assay. abstract: Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to occur, making it one of the WHO´s targets for accelerated vaccine development. One vaccine candidate is based on live-attenuated measles virus (MV) vaccine encoding the MERS-CoV spike glycoprotein (MERS-S). MV(vac2)-MERS-S(H) induces robust humoral and cellular immunity against MERS-S mediating protection. Here, the induction and nature of immunity after vaccination with MV(vac2)-MERS-S(H) or novel MV(vac2)-MERS-N were further characterized. We focused on the necessity for vector replication and the nature of induced T cells, since functional CD8(+) T cells contribute importantly to clearance of MERS-CoV. While no immunity against MERS-CoV or MV was detected in MV-susceptible mice after immunization with UV-inactivated virus, replication-competent MV(vac2)-MERS-S(H) triggered robust neutralizing antibody titers also in adult mice. Furthermore, a significant fraction of MERS CoV-specific CD8(+) T cells and MV-specific CD4(+) T cells simultaneously expressing IFN-γ and TNF-α were induced, revealing that MV(vac2)-MERS-S(H) induces multifunctional cellular immunity. url: https://www.sciencedirect.com/science/article/pii/S0042682218301697 doi: 10.1016/j.virol.2018.05.028 id: cord-310942-191m0e65 author: Boga, Jose Antonio title: Beneficial actions of melatonin in the management of viral infections: a new use for this “molecular handyman”? date: 2012-04-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Melatonin (N‐acetyl‐5‐methoxytryptamine) is a multifunctional signaling molecule that has a variety of important functions. Numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. Clinical trials have shown that melatonin is efficient in preventing cell damage under acute (sepsis, asphyxia in newborns) and chronic states (metabolic and neurodegenerative diseases, cancer, inflammation, aging). The beneficial effects of melatonin can be explained by its properties as a potent antioxidant and antioxidant enzyme inducer, a regulator of apoptosis and a stimulator of immune functions. These effects support the use of melatonin in viral infections, which are often associated with inflammatory injury and increases in oxidative stress. In fact, melatonin has been used recently to treat several viral infections, which are summarized in this review. The role of melatonin in infections is also discussed herein. Copyright © 2012 John Wiley & Sons, Ltd. url: https://www.ncbi.nlm.nih.gov/pubmed/22511571/ doi: 10.1002/rmv.1714 id: cord-346212-mcnr7bcp author: Bonzano, Chiara title: Doxycycline: From Ocular Rosacea to COVID-19 Anosmia. New Insight Into the Coronavirus Outbreak date: 2020-05-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32574320/ doi: 10.3389/fmed.2020.00200 id: cord-271970-i35pic5o author: Boris, Bonaventure title: A genome-wide CRISPR/Cas9 knock-out screen identifies the DEAD box RNA helicase DDX42 as a broad antiviral inhibitor date: 2020-10-28 words: 6320.0 sentences: 343.0 pages: flesch: 52.0 cache: ./cache/cord-271970-i35pic5o.txt txt: ./txt/cord-271970-i35pic5o.txt summary: Depletion of endogenous DDX42 using siRNA or CRISPR/Cas9 knock-out increased HIV-1 infection, both in model cell lines and in physiological targets of HIV-1, primary CD4+ T cells and monocyte-derived macrophages (MDMs), and irrespectively of the IFN treatment. Deep sequencing analysis of the GeCKO cell populations showed more than 94% coverage for both libraries (≥ 10 reads for 61,598 and 54,609 sgRNA-coding sequences out of GeCKO populations were subjected to type 1 IFN treatment in order to induce the antiviral state and, 24h later, incubated with VSV-G-pseudotyped, HIV-1 based LVs coding for an antibiotic resistance cassette. In order to validate the effect of DDX42 KO on HIV-1 infection in another model cell line, two additional sgRNAs were designed (sgRNA-2 and -3) and used in parallel to the one identified in the GeCKO screen (sgDDX42-1) (Figure 2A ). abstract: Genome-wide CRISPR/Cas9 knock-out genetic screens are powerful approaches to unravel new regulators of viral infections. With the aim of identifying new cellular inhibitors of HIV-1, we have developed a strategy in which we took advantage of the ability of type 1 interferon (IFN) to potently inhibit HIV-1 infection, in order to create a cellular environment hostile to viral replication. This approach led to the identification of the DEAD-box RNA helicase DDX42 as an intrinsic inhibitor of HIV-1. Depletion of endogenous DDX42 using siRNA or CRISPR/Cas9 knock-out increased HIV-1 infection, both in model cell lines and in physiological targets of HIV-1, primary CD4+ T cells and monocyte-derived macrophages (MDMs), and irrespectively of the IFN treatment. Similarly, the overexpression of a dominant-negative mutant of DDX42 positively impacted HIV-1 infection, whereas wild-type DDX42 overexpression potently inhibited HIV-1 infection. The positive impact of endogenous DDX42 depletion on HIV-1 infection was directly correlated to an increase in viral DNA accumulation. Interestingly, proximity ligation assays showed that DDX42, which can be mainly found in the nucleus but is also present in the cytoplasm, was in the close vicinity of HIV-1 Capsid during infection of primary monocyte-derived macrophages. Moreover, we show that DDX42 is also able to substantially decrease infection with other retroviruses and retrotransposition of long interspersed elements-1 (LINE-1). Finally, we reveal that DDX42 potently inhibits other pathogenic viruses, including Chikungunya virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). url: https://doi.org/10.1101/2020.10.28.359356 doi: 10.1101/2020.10.28.359356 id: cord-048489-ajafw966 author: Bozza, Fernando A title: Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity date: 2008-06-25 words: 4936.0 sentences: 261.0 pages: flesch: 45.0 cache: ./cache/cord-048489-ajafw966.txt txt: ./txt/cord-048489-ajafw966.txt summary: title: Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity RESULTS: IL-1β, IFN-γ, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue) when compared to mild disease forms (mild dengue). Analysis of factors independently associated with dengue severity and other clinical manifestations was performed with GLM with logistic regression or Gaussian family. In order to avoid effects due to differences in the blood collection time, we compared mild and severe dengue patient groups using Mann-Whitney U Test, which showed no differences in the disease onset time at the moment of sample collection [see Additional file 1]. We studied the cytokine profile from Brazilian patients in order to compare severe and mild dengue cases during the acute phase of the disease. In the present study, the use of a multiplex analysis for cytokine plasma detection in patients with dengue could identify cytokine profiles associated with the disease severity. abstract: BACKGROUND: Dengue virus pathogenesis is not yet fully understood and the identification of patients at high risk for developing severe disease forms is still a great challenge in dengue patient care. During the present study, we evaluated prospectively the potential of cytokines present in plasma from patients with dengue in stratifying disease severity. METHODS: Seventeen-cytokine multiplex fluorescent microbead immunoassay was used for the simultaneous detection in 59 dengue patients. GLM models using bimodal or Gaussian family were determined in order to associate cytokines with clinical manifestations and laboratory diagnosis. RESULTS: IL-1β, IFN-γ, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue) when compared to mild disease forms (mild dengue). In contrast, increased MIP-1β levels were observed in patients with mild dengue. MIP-1β was also associated with CD56+NK cell circulating rates. IL-1β, IL-8, TNF-α and MCP-1 were associated with marked thrombocytopenia. Increased MCP-1 and GM-CSF levels correlated with hypotension. Moreover, MIP-1β and IFN-γ were independently associated with both dengue severity and disease outcome. CONCLUSION: Our data demonstrated that the use of a multiple cytokine assay platform was suitable for identifying distinct cytokine profiles associated with the dengue clinical manifestations and severity. MIP-β is indicated for the first time as a good prognostic marker in contrast to IFN-γ that was associated with disease severity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474613/ doi: 10.1186/1471-2334-8-86 id: cord-103511-31njndob author: Broggi, Achille title: Type III interferons disrupt the lung epithelial barrier upon viral recognition date: 2020-05-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Lower respiratory tract infections are a leading cause of mortality driven by infectious agents. RNA viruses such as influenza virus, respiratory syncytial virus and the new pandemic coronavirus SARS-CoV-2 can be highly pathogenic. Clinical and experimental evidence indicate that most severe and lethal cases do not depend on the viral burden and are, instead, characterized by an aberrant immune response. In this work we assessed how the innate immune response contributes to the pathogenesis of RNA virus infections. We demonstrate that type III interferons produced by dendritic cells in the lung in response to viral recognition cause barrier damage and compromise the host tissue tolerance. In particular, type III interferons inhibit tissue repair and lung epithelial cell proliferation, causing susceptibility to lethal bacterial superinfections. Overall, our data give a strong mandate to rethink the pathophysiological roles of this group of interferons and their possible use in the clinical practice against endemic as well as emerging viral infections. url: https://doi.org/10.1101/2020.05.05.077867 doi: 10.1101/2020.05.05.077867 id: cord-253335-wgqierp6 author: Brook, Cara E title: Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence date: 2020-02-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats’ virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-transmitting viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats. url: https://doi.org/10.7554/elife.48401 doi: 10.7554/elife.48401 id: cord-257662-viy65y72 author: Burrack, Kristina S. title: The Role of Myeloid Cell Activation and Arginine Metabolism in the Pathogenesis of Virus-Induced Diseases date: 2014-09-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: When an antiviral immune response is generated, a balance must be reached between two opposing pathways: the production of proinflammatory and cytotoxic effectors that drive a robust antiviral immune response to control the infection and regulators that function to limit or blunt an excessive immune response to minimize immune-mediated pathology and repair tissue damage. Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). Nitric oxide (NO) production by iNOS is an important proinflammatory mediator, whereas Arg1-expressing macrophages contribute to the resolution of inflammation and wound repair. In the context of viral infections, expression of these enzymes can result in a variety of outcomes for the host. NO has direct antiviral properties against some viruses, whereas during other virus infections NO can mediate immunopathology and/or inhibit the antiviral immune response to promote chronic infection. Arg1 activity not only has important wound healing functions but can also inhibit the antiviral immune response during some viral infections. Thus, depending on the specific virus and the tissue(s) involved, the activity of both of these arginine-hydrolyzing enzymes can either exacerbate or limit the severity of virus-induced disease. In this review, we will discuss a variety of viral infections, including HIV, SARS-CoV, LCMV, HCV, RSV, and others, where myeloid cells influence the control and clearance of the virus from the host, as well as the severity and resolution of tissue damage, via the activities of iNOS and/or Arg1. Clearly, monocyte/macrophage activation and arginine metabolism will continue to be important areas of investigation in the context of viral infections. url: https://www.ncbi.nlm.nih.gov/pubmed/25250029/ doi: 10.3389/fimmu.2014.00428 id: cord-257220-fe2sacjj author: Butler, J. E. title: Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic date: 2014-07-01 words: 19650.0 sentences: 994.0 pages: flesch: 44.0 cache: ./cache/cord-257220-fe2sacjj.txt txt: ./txt/cord-257220-fe2sacjj.txt summary: LDV elevates IgG levels in mice with little production of virus-specific antibodies [11, 21] , which is almost identical to what is seen in isolator piglets infected with PRRSV [22] (''''The effect of age, rearing, complement and the role of mucosal immunity'''' section). Polyclonal activation of B cells occurs in lymphoid organs from porcine reproductive and respiratory syndrome virus (PRRSV)-induced pigs The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells Antigen-specific B cell responses to porcine reproductive and respiratory syndrome virus infection Antibody production and blastogenesis response in pigs experimentally infected with porcine reproductive and respiratory syndrome virus Neutralizing antibody responses of pigs infected with natural GP5 N-glycan mutants of porcine reproductive and respiratory syndrome virus abstract: Porcine reproductive and respiratory disease syndrome (PRRS) is a viral pandemic that especially affects neonates within the “critical window” of immunological development. PRRS was recognized in 1987 and within a few years became pandemic causing an estimated yearly $600,000 economic loss in the USA with comparative losses in most other countries. The causative agent is a single-stranded, positive-sense enveloped arterivirus (PRRSV) that infects macrophages and plasmacytoid dendritic cells. Despite the discovery of PRRSV in 1991 and the publication of >2,000 articles, the control of PRRS is problematic. Despite the large volume of literature on this disease, the cellular and molecular mechanisms describing how PRRSV dysregulates the host immune system are poorly understood. We know that PRRSV suppresses innate immunity and causes abnormal B cell proliferation and repertoire development, often lymphopenia and thymic atrophy. The PRRSV genome is highly diverse, rapidly evolving but amenable to the generation of many mutants and chimeric viruses for experimental studies. PRRSV only replicates in swine which adds to the experimental difficulty since no inbred well-defined animal models are available. In this article, we summarize current knowledge and apply it toward developing a series of provocative and testable hypotheses to explain how PRRSV immunomodulates the porcine immune system with the goal of adding new perspectives on this disease. url: https://www.ncbi.nlm.nih.gov/pubmed/24981123/ doi: 10.1007/s12026-014-8549-5 id: cord-285744-jpw8hen9 author: Byeon, Jung Hye title: Comparison of cytokine responses in nasopharyngeal aspirates from children with viral lower respiratory tract infections date: 2009-01-13 words: 3314.0 sentences: 179.0 pages: flesch: 46.0 cache: ./cache/cord-285744-jpw8hen9.txt txt: ./txt/cord-285744-jpw8hen9.txt summary: Aim: To determine whether nasopharyngeal aspirates (NPAs) cytokine response is different according to the causative viruses in children with lower respiratory tract infections (LRTI). Several studies (1-3) have investigated cytokine profiles in nasopharyngeal aspirates (NPAs) during viral lower respiratory tract infections (LRTI) in children. Previous studies (1, 3) were demonstrated that patients with respiratory syncytial virus (RSV) infection and those with influenza virus infection induce different cytokine profiles. The present study was performed to determine whether clinical responses in children with LRTI would differ according to causative viruses and to examine the differential patterns of IL-4, IL-5 and IFN-γ concentrations in NPA during acute viral lower respiratory infections according to the causative organisms. The present study of viral LRTI children indicated that as seen in NPAs local inflammatory cytokine responses differed according to the causative organisms. abstract: Aim: To determine whether nasopharyngeal aspirates (NPAs) cytokine response is different according to the causative viruses in children with lower respiratory tract infections (LRTI). Methods: NPAs from 277 children with LRTI caused by respiratory virus were evaluated. Based on the proven viral agents, LRTI patients were divided into four groups. Levels of IL‐4, IL‐5 and IFN‐γ were determined by ELISA. Results: Patients with influenza virus infection demonstrated significantly lower IL‐4 and IL‐5 levels than those with other three groups. Patients with respiratory syncytial virus (RSV) infection showed an increase in production of IL‐4 and IL‐5, and a decrease in the IFN‐γ level when compared to patients with influenza virus infection. Interestingly, a similar Th2 response was seen in patients with parainfluenza virus or adenovirus infection. Conclusion: These results demonstrate that respiratory viruses can induce different local cytokine responses. However, Th2 biased responses are not unique for RSV but seem to be predominant in respiratory viruses of young children. url: https://www.ncbi.nlm.nih.gov/pubmed/19183120/ doi: 10.1111/j.1651-2227.2008.01208.x id: cord-000103-3zh8jmc2 author: Caignard, Grégory title: Differential Regulation of Type I Interferon and Epidermal Growth Factor Pathways by a Human Respirovirus Virulence Factor date: 2009-09-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma. To understand the molecular pathogenesis of these infections, we searched for cellular targets of the virulence protein C of human parainfluenza virus type 3 (hPIV3-C). We found that hPIV3-C interacts directly through its C-terminal domain with STAT1 and GRB2, whereas C proteins from measles or Nipah viruses failed to do so. Binding to STAT1 explains the previously reported capacity of hPIV3-C to block type I interferon signaling, but the interaction with GRB2 was unexpected. This adaptor protein bridges Epidermal Growth Factor (EGF) receptor to MAPK/ERK pathway, a signaling cascade recently found to be involved in airway inflammatory response. We report that either hPIV3 infection or transient expression of hPIV3-C both increase cellular response to EGF, as assessed by Elk1 transactivation and phosphorylation levels of ERK1/2, 40S ribosomal subunit protein S6 and translation initiation factor 4E (eIF4E). Furthermore, inhibition of MAPK/ERK pathway with U0126 prevented viral protein expression in infected cells. Altogether, our data provide molecular basis to explain the role of hPIV3-C as a virulence factor and determinant of pathogenesis and demonstrate that Paramyxoviridae have evolved a single virulence factor to block type I interferon signaling and to boost simultaneous cellular response to growth factors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736567/ doi: 10.1371/journal.ppat.1000587 id: cord-023724-5at0rhqk author: Cann, Alan J. title: Infection date: 2015-07-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Virus infection of higher organisms is the cumulative result of all the processes of replication and gene expression described in the previous chapters. Together, these determine the overall course of each infection. Infections range in complexity and duration from a very brief, superficial interaction between the virus and its host to infections that may span the entire life of the host organism, from before birth to its eventual death. A common misconception is that virus infection inevitably results in disease. In reality, the reverse is true—only a small minority of virus infections gives rise to any disease symptoms. This chapter provides an overview of the numerous patterns of virus infection and forms an introduction to the discussion of virus pathogenesis in Chapter 7. Unlike previous and subsequent chapters, this chapter deals primarily with the interaction of viruses with intact organisms rather than with the molecular biologist’s usual concern about the interaction between a virus and the cell. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173531/ doi: 10.1016/b978-0-12-801946-7.00006-7 id: cord-305315-0qt7eth0 author: Cao, Liyan title: Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-β production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway date: 2015-08-18 words: 4245.0 sentences: 277.0 pages: flesch: 53.0 cache: ./cache/cord-305315-0qt7eth0.txt txt: ./txt/cord-305315-0qt7eth0.txt summary: title: Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-β production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway In this study, porcine small intestinal epithelial cells (IECs), the target cells of PEDV, were used as the infection model in vitro to identify the possible molecular mechanisms of PEDV-inhibition IFN-β production. CONCLUSION: Taken together, our data demonstrated for the first time that PEDV infection of its target cell line, IECs, inhibited dsRNA-mediated IFN-β production by blocking the activation of IPS-1 in RIG-I-mediated pathway. PEDV failed to induce IFN-β expression and inhibited poly (I:C)-mediated IFN-β production in IECs Type I IFNs (IFN-α/β) are critical to the host antiviral innate immune response. In summary, the findings of the present study suggested that PEDV-infection in IECs inhibits dsRNA-induced IFN-β induction by interfering with IRF-3 activity associated with RIG-I-mediated signaling pathway. abstract: BACKGROUND: The lack of optimal porcine cell lines has severely impeded the study and progress in elucidation of porcine epidemic diarrhea virus (PEDV) pathogenesis. Vero cell, an African green monkey kidney cell line, was often used to isolate and propagate PEDV. Nonetheless, the target cells of PEDV in vivo are intestinal epithelial cells, during infection, intestinal epithelia would be damaged and resulted in digestive disorders. The immune functions of porcine epithelial cells and interactions with other immune cell populations display a number of differences compared to other species. Type I interferon (IFN) plays an important role in antiviral immune response. Limited reports showed that PEDV could inhibit type I interferon production. In this study, porcine small intestinal epithelial cells (IECs), the target cells of PEDV, were used as the infection model in vitro to identify the possible molecular mechanisms of PEDV-inhibition IFN-β production. RESULTS: PEDV not only failed to induce IFN-β expression, but also inhibited dsRNA-mediated IFN-β production in IECs. As the key IFN-β transcription factors, we found that dsRNA-induced activation of IFN regulatory factor 3 (IRF-3) was inhibited after PEDV infection, but not nuclear factor-kappaB (NF-κB). To identify the mechanism of PEDV intervention with dsRNA-mediated IFN-β expression more accurately, the role of individual molecules of RIG-I signaling pathway were investigated. In the upstream of IRF-3, TANK-binding kinase 1 (TBK1)-or inhibitor of κB kinase-ε (IKKε)-mediated IFN-β production was not blocked by PEDV, while RIG-I-and its adapter molecule IFN-β promoter stimulator 1 (IPS-1)-mediated IFN-β production were completely inhibited after PEDV infection. CONCLUSION: Taken together, our data demonstrated for the first time that PEDV infection of its target cell line, IECs, inhibited dsRNA-mediated IFN-β production by blocking the activation of IPS-1 in RIG-I-mediated pathway. Our studies offered new visions in understanding of the interaction between PEDV and host innate immune system. url: https://doi.org/10.1186/s12985-015-0345-x doi: 10.1186/s12985-015-0345-x id: cord-340475-h0q1m3ed author: Carnero, Elena title: Type I Interferon Regulates the Expression of Long Non-Coding RNAs date: 2014-11-06 words: 10164.0 sentences: 544.0 pages: flesch: 55.0 cache: ./cache/cord-340475-h0q1m3ed.txt txt: ./txt/cord-340475-h0q1m3ed.txt summary: Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response.These genes are induced in response to different doses of IFNα2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. HuH7 cells were treated for 6, 24, 48, or 72 h with increasing doses of IFNα2 up to 10,000 units/ml, and the expression levels of GBP1, IRF1, BST2, OAS, IL6, and ISG15 were evaluated by qRT-PCR (Figure 1) . abstract: Interferons (IFNs) are key players in the antiviral response. IFN sensing by the cell activates transcription of IFN-stimulated genes (ISGs) able to induce an antiviral state by affecting viral replication and release. IFN also induces the expression of ISGs that function as negative regulators to limit the strength and duration of IFN response. The ISGs identified so far belong to coding genes. However, only a small proportion of the transcriptome corresponds to coding transcripts and it has been estimated that there could be as many coding as long non-coding RNAs (lncRNAs). To address whether IFN can also regulate the expression of lncRNAs, we analyzed the transcriptome of HuH7 cells treated or not with IFNα2 by expression arrays. Analysis of the arrays showed increased levels of several well-characterized coding genes that respond to IFN both at early or late times. Furthermore, we identified several IFN-stimulated or -downregulated lncRNAs (ISRs and IDRs). Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response. These genes are induced in response to different doses of IFNα2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. IFNβ also induced the expression of these lncRNAs. ISR2 and 8 were also induced by an influenza virus unable to block the IFN response but not by other wild-type lytic viruses tested. Surprisingly, both ISR2 and 8 were significantly upregulated in cultured cells and livers from patients infected with HCV. Increased levels of ISR2 were also detected in patients chronically infected with HIV. This is relevant as genome-wide guilt-by-association studies predict that ISR2, 8, and 12 may function in viral processes, in the IFN pathway and the antiviral response. Therefore, we propose that these lncRNAs could be induced by IFN to function as positive or negative regulators of the antiviral response. url: https://www.ncbi.nlm.nih.gov/pubmed/25414701/ doi: 10.3389/fimmu.2014.00548 id: cord-252268-o63ep08b author: Carolan, Louise A. title: TaqMan real time RT-PCR assays for detecting ferret innate and adaptive immune responses date: 2014-09-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ferret is an excellent model for many human infectious diseases including influenza, SARS-CoV, henipavirus and pneumococcal infections. The ferret is also used to study cystic fibrosis and various cancers, as well as reproductive biology and physiology. However, the range of reagents available to measure the ferret immune response is very limited. To address this deficiency, high-throughput real time RT-PCR TaqMan assays were developed to measure the expression of fifteen immune mediators associated with the innate and adaptive immune responses (IFNα, IFNβ, IFNγ, IL1α, IL1β, IL2, IL4, IL6, IL8, IL10, IL12p40, IL17, Granzyme A, MCP1, TNFα), as well as four endogenous housekeeping genes (ATF4, HPRT, GAPDH, L32). These assays have been optimized to maximize reaction efficiency, reduce the amount of sample required (down to 1 ng RNA per real time RT-PCR reaction) and to select the most appropriate housekeeping genes. Using these assays, the expression of each of the tested genes could be detected in ferret lymph node cells stimulated with mitogens or infected with influenza virus in vitro. These new tools will allow a more comprehensive analysis of the ferret immune responses following infection or in other disease states. url: https://doi.org/10.1016/j.jviromet.2014.04.014 doi: 10.1016/j.jviromet.2014.04.014 id: cord-001124-qcjbtflt author: Carrero, Javier Antonio title: Confounding roles for type I interferons during bacterial and viral pathogenesis date: 2013-10-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Although type I interferons (IFN-I) were initially defined as potent antiviral agents, they can also cause decreased host resistance to some bacterial and viral infections. The many antiviral functions of the IFN-I include direct suppression of viral replication and activation of the immune response against viruses. In addition to their antiviral effects, IFN-I are also protective against several extracellular bacterial infections, in part, by promoting the induction of TNF-α and nitric oxide. In contrast, there is a negative effect of IFN-I on host resistance during chronic infection with lymphocytic choriomeningitis virus (LCMV) and acute infections with intracellular bacteria. In the case of LCMV, chronic IFN-I signaling induces adaptive immune system suppression. Blockade of IFN-I signaling removes the suppression and allows CD4 T-cell- and IFN-γ-mediated resolution of the infection. During acute intracellular bacterial infection, IFN-I suppress innate immunity by at least two defined mechanisms. During Francisella infection, IFN-I prevent IL-17 upregulation on γδ T cells and neutrophil recruitment. Following Listeria infection, IFN-I promote the cell death of macrophages and lymphocytes, which leads to innate immune suppression. These divergent findings for the role of IFN-I on pathogen control emphasize the complexity of the interferons system and force more mechanistic evaluation of its role in pathogenesis. This review evaluates IFN-I during infection with an emphasis on work carried out IFN-I-receptor-deficient mice. url: https://academic.oup.com/intimm/article-pdf/25/12/663/2038704/dxt050.pdf doi: 10.1093/intimm/dxt050 id: cord-007013-tlvgyzft author: Chan, Kok Fei title: Investigating Viral Interference Between Influenza A Virus and Human Respiratory Syncytial Virus in a Ferret Model of Infection date: 2018-08-01 words: 4939.0 sentences: 320.0 pages: flesch: 49.0 cache: ./cache/cord-007013-tlvgyzft.txt txt: ./txt/cord-007013-tlvgyzft.txt summary: Previously, we used the ferret model to demonstrate that viral interference can occur following infection with human influenza A and B viruses and will prevent, delay, or limit subsequent infection with an influenza virus of a different type, subtype, or lineage [10, 11] . The peak of hRSV shedding was delayed in ferrets infected with A(H1N1)pdm09 followed by hRSV as compared to control animals infected with hRSV alone (median, 8 vs 6 days; P = .0091 by the Mann-Whitney test; Figure 2Ci ). The median duration of A(H1N1)pdm09 shedding was increased in ferrets infected with hRSV followed by A(H1N1)pdm09 as compared to control animals infected with A(H1N1)pdm09 alone (8 vs 7 days; P = .0196 by the Mann-Whitney test; Figure 2Civ ). Notably, increased expression of inflammatory mediators following infection with influenza virus as compared to hRSV has been observed in studies assessing human clinical samples and in vitro airway epithelial cell cultures [36] [37] [38] [39] . abstract: Epidemiological studies have observed that the seasonal peak incidence of influenza virus infection is sometimes separate from the peak incidence of human respiratory syncytial virus (hRSV) infection, with the peak incidence of hRSV infection delayed. This is proposed to be due to viral interference, whereby infection with one virus prevents or delays infection with a different virus. We investigated viral interference between hRSV and 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) in the ferret model. Infection with A(H1N1)pdm09 prevented subsequent infection with hRSV. Infection with hRSV reduced morbidity attributed to infection with A(H1N1)pdm09 but not infection, even when an increased inoculum dose of hRSV was used. Notably, infection with A(H1N1)pdm09 induced higher levels of proinflammatory cytokines, chemokines, and immune mediators in the ferret than hRSV. Minimal cross-reactive serological responses or interferon γ–expressing cells were induced by either virus ≥14 days after infection. These data indicate that antigen-independent mechanisms may drive viral interference between unrelated respiratory viruses that can limit subsequent infection or disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107400/ doi: 10.1093/infdis/jiy184 id: cord-347460-9vechh4x author: Chang, Feng-Yee title: Immunologic aspects of characteristics, diagnosis, and treatment of coronavirus disease 2019 (COVID-19) date: 2020-06-04 words: 8050.0 sentences: 384.0 pages: flesch: 43.0 cache: ./cache/cord-347460-9vechh4x.txt txt: ./txt/cord-347460-9vechh4x.txt summary: Three components are crucial for SARS-CoV induced diseases: 1) the role of CD8+ T cells in defense against the virus, which causes apoptosis in the infected cells, 2) interactions of the virus with macrophages and dendritic cells, which initiate the early innate and subsequent adaptive immune responses, and 3) type I interferon (IFN) system, an innate response against viral infections, which can inhibit virus replication in the early phase. Existing information suggests that the SARS-CoV-infected airways and alveolar epithelial cells secrete abundant chemokines to attract immune cell infiltrations to the lungs, including macrophages and neutrophils, thereby causing damage due to high levels of proinflammatory cytokines and other mediators secreted by these cell types. After a decade of research on coronavirus, unfortunately, still there are no licensed vaccines, effective specific antivirals, nor drug combinations supported by high-level evidence to treat the infection, especially for newly emerging strains such as SARS-COV-2 [59] . abstract: On March 11, 2020, the World Health Organization declared the worldwide spread of the infectious disease COVID-19, caused by a new strain of coronavirus, SARS-CoV-2, as a pandemic. Like in all other infectious diseases, the host immune system plays a key role in our defense against SARS-CoV-2 infection. However, viruses are able to evade the immune attack and proliferate and, in susceptible individuals, cause severe inflammatory response known as cytokine storm, particularly in the lungs. The advancement in our understanding of the mechanisms underlying the host immune responses promises to facilitate the development of approaches for prevention or treatment of diseases. Components of immune system, such as antibodies, can also be used to develop sensitive and specific diagnostic methods as well as novel therapeutic agents. In this review, we summarize our knowledge about how the host mounts immune responses to infection by SARS-CoV-2. We also describe the diagnostic methods being used for COVID-19 identification and summarize the current status of various therapeutic strategies, including vaccination, being considered for treatment of the disease. url: https://doi.org/10.1186/s12929-020-00663-w doi: 10.1186/s12929-020-00663-w id: cord-327685-fymfqvp3 author: Channappanavar, Rudragouda title: Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology date: 2017-05-02 words: 5834.0 sentences: 288.0 pages: flesch: 33.0 cache: ./cache/cord-327685-fymfqvp3.txt txt: ./txt/cord-327685-fymfqvp3.txt summary: In contrast, highly pathogenic hCoVs such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) predominantly infect lower airways and cause fatal pneumonia. Severe pneumonia caused by pathogenic hCoVs is often associated with rapid virus replication, massive inflammatory cell infiltration and elevated pro-inflammatory cytokine/chemokine responses resulting in acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Although there is no direct evidence for the involvement of pro-inflammatory cytokines and chemokines in lung pathology during SARS and MERS, correlative evidence from patients with severe disease suggests a role for hyper-inflammatory responses in hCoV pathogenesis. Infection of non-human primates (NHPs) with SARS-CoV induced a dysregulated immune response resulting in increased disease severity in aged but not young NHPs, despite similar viral titers in the airways [67] . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice abstract: Human coronaviruses (hCoVs) can be divided into low pathogenic and highly pathogenic coronaviruses. The low pathogenic CoVs infect the upper respiratory tract and cause mild, cold-like respiratory illness. In contrast, highly pathogenic hCoVs such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) predominantly infect lower airways and cause fatal pneumonia. Severe pneumonia caused by pathogenic hCoVs is often associated with rapid virus replication, massive inflammatory cell infiltration and elevated pro-inflammatory cytokine/chemokine responses resulting in acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Recent studies in experimentally infected animal strongly suggest a crucial role for virus-induced immunopathological events in causing fatal pneumonia after hCoV infections. Here we review the current understanding of how a dysregulated immune response may cause lung immunopathology leading to deleterious clinical manifestations after pathogenic hCoV infections. url: https://www.ncbi.nlm.nih.gov/pubmed/28466096/ doi: 10.1007/s00281-017-0629-x id: cord-260109-vgbrwegt author: Charley, B. title: Characterization of blood mononuclear cells producing IFNα following induction by coronavirus-infected cells (porcine transmissible gastroenteritis virus) date: 1990-02-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Porcine blood mononuclear cells (PBMC) were shown to produce interferon-α (IFNα) following incubation with cells infected by a coronavirus, transmissible gastroenteritis virus. Monoclonal antibodies (mAb) with specificities for leukocyte subsets and major histocompatibility complex (MHC) antigens were used to characterize IFNα producer cells. The production of IFNα was found to be a function of non-phagocytic, non-adherent, non-T, non-B, CD4+ (and to a lesser extent CD8+) MHC-class-II-positive cells. Furthermore, addition of anti-MHC (class II) mAb during PBMC incubation with virus-infected cells reduced IFN yields, suggesting that masking of these surface antigens alters PBMC responsiveness to IFN induction. url: https://www.ncbi.nlm.nih.gov/pubmed/2167506/ doi: 10.1016/0923-2494(90)90133-j id: cord-012909-o6t2srim author: Chaudhari, Jayeshbhai title: Host Transcriptional Response to Persistent Infection with a Live-Attenuated Porcine Reproductive and Respiratory Syndrome Virus Strain date: 2020-07-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Both virulent and live-attenuated porcine reproductive and respiratory syndrome virus (PRRSV) strains can establish persistent infection in lymphoid tissues of pigs. To investigate the mechanisms of PRRSV persistence, we performed a transcriptional analysis of inguinal lymphoid tissue collected from pigs experimentally infected with an attenuated PRRSV strain at 46 days post infection. A total of 6404 differentially expressed genes (DEGs) were detected of which 3960 DEGs were upregulated and 2444 DEGs were downregulated. Specifically, genes involved in innate immune responses and chemokines and receptors associated with T-cell homing to lymphoid tissues were down regulated. As a result, homing of virus-specific T-cells to lymphoid tissues seems to be ineffective, evidenced by the lower frequencies of virus-specific T-cell in lymphoid tissue than in peripheral blood. Genes associated with T-cell exhaustion were upregulated. Likewise, genes involved in the anti-apoptotic pathway were upregulated. Collectively, the data suggested that the live-attenuated PRRSV strain establishes a pro-survival microenvironment in lymphoid tissue by suppressing innate immune responses, T-cell homing, and preventing cell apoptosis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474429/ doi: 10.3390/v12080817 id: cord-279781-5ldpz9m9 author: Chen, Chi-Yuan title: Baculovirus as a gene delivery vector: Recent understandings of molecular alterations in transduced cells and latest applications date: 2011-04-28 words: 13111.0 sentences: 665.0 pages: flesch: 38.0 cache: ./cache/cord-279781-5ldpz9m9.txt txt: ./txt/cord-279781-5ldpz9m9.txt summary: Concurrent with the aforementioned findings, we also discovered that baculovirus transduction of human BMSCs disturbed the expression of 816 genes, most of which were related to 5 signaling pathways: cell adhesion molecules, TLR, Jak-STAT, apoptosis as well as antigen processing and presentation (Chen et al., 2009b) . immunization of chickens with another VSVG-pseudotyped baculovirus expressing HA of H5N1 avian influenza virus (AIV) also evoked significantly higher levels of H5-specific antibody and cellular immunity than those receiving DNA vaccines, and conferred protection against lethal challenge with the homologous virus strain (Wu et al., 2009b) . Transient and stable gene expression in mammalian cells transduced with a recombinant baculovirus vector Baculovirus as a highly efficient gene delivery vector for the expression of hepatitis delta virus antigens in mammalian cells abstract: Baculovirus infects insects in nature and is non-pathogenic to humans, but can transduce a broad range of mammalian and avian cells. Thanks to the biosafety, large cloning capacity, low cytotoxicity and non-replication nature in the transduced cells as well as the ease of manipulation and production, baculovirus has gained explosive popularity as a gene delivery vector for a wide variety of applications. This article extensively reviews the recent understandings of the molecular mechanisms pertinent to baculovirus entry and cellular responses, and covers the latest advances in the vector improvements and applications, with special emphasis on antiviral therapy, cancer therapy, regenerative medicine and vaccine. url: https://doi.org/10.1016/j.biotechadv.2011.04.004 doi: 10.1016/j.biotechadv.2011.04.004 id: cord-356094-sbtigcfr author: Chen, Huijie title: Antiviral Activity Against Infectious Bronchitis Virus and Bioactive Components of Hypericum perforatum L. date: 2019-10-29 words: 8921.0 sentences: 485.0 pages: flesch: 55.0 cache: ./cache/cord-356094-sbtigcfr.txt txt: ./txt/cord-356094-sbtigcfr.txt summary: perforatum was ethyl acetate extraction section (HPE), and results showed that treatment with HPE significantly reduced the relative messenger ribonucleic acid (mRNA) expression and virus titer of IBV, and reduced positive green immunofluorescence signal of IBV in chicken embryo kidney (CEK) cells. The results of adaptation and replication in CEK cells, such as CPE, reverse transcription polymerase chain reaction (RT-PCR), and IBV growth curve determined by tissue culture infective dose (TCID 50 ) at different time were tested. The relative mRNA expression level of IBV-N gene was detected by qRT-PCR and the virus titer of IBV was determined by TCID 50 to analyze the antiviral effect of HPE, HPW and SEE (Figure 3) . FIgUre 8 | The effects of Hypericum perforatum ethyl acetate (HPE) on infectious bronchitis virus (IBV) messenger ribonucleic acid (mRNA) expression levels of trachea (A) and kidney (B). abstract: Hypericum perforatum L., also known as Saint John’s Wort, has been well studied for its chemical composition and pharmacological activity. In this study, the antiviral activities of H. perforatum on infectious bronchitis virus (IBV) were evaluated in vitro and in vivo for the first time. The results of in vitro experiments confirmed that the antiviral component of H. perforatum was ethyl acetate extraction section (HPE), and results showed that treatment with HPE significantly reduced the relative messenger ribonucleic acid (mRNA) expression and virus titer of IBV, and reduced positive green immunofluorescence signal of IBV in chicken embryo kidney (CEK) cells. HPE treatment at doses of 480–120 mg/kg for 5 days, reduced IBV induced injury in the trachea and kidney, moreover, reduced the mRNA expression level of IBV in the trachea and kidney in vivo. The mRNA expression levels of IL-6, tumor necrosis factor alpha (TNF-α), and nuclear factor kappa beta (NF-κB) significantly decreased, but melanoma differentiation-associated protein 5 (MDA5), mitochondrial antiviral signaling gene, interferon alpha (IFN-α), and interferon beta (IFN-β) mRNA levels significantly increased in vitro and in vivo. Our findings demonstrated that HPE had significant anti-IBV effects in vitro and in vivo, respectively. In addition, it is possible owing to up-regulate mRNA expression of type I interferon through the MDA5 signaling pathway and down-regulate mRNA expression of IL-6 and TNF-α via the NF-κB signaling pathway. Moreover, the mainly active compositions of HPE analyzed by high-performance liquid chromatography/electrospray ionization–mass spectroscopy (ESI-MS) are hyperoside, quercitrin, quercetin, pseudohypericin, and hypericin, and a combination of these compounds could mediate the antiviral activities. This might accelerate our understanding of the antiviral effect of H. perforatum and provide new insights into the development of effective therapeutic strategies. url: https://www.ncbi.nlm.nih.gov/pubmed/31736754/ doi: 10.3389/fphar.2019.01272 id: cord-002670-rjrw875d author: Chen, Jidang title: Immunosuppression by viral N proteins date: 2017-06-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584132/ doi: 10.18632/oncotarget.18597 id: cord-353957-0pjg25kn author: Chen, Shilong title: Avian Interferon-Inducible Transmembrane Protein Family Effectively Restricts Avian Tembusu Virus Infection date: 2017-04-20 words: 6563.0 sentences: 381.0 pages: flesch: 53.0 cache: ./cache/cord-353957-0pjg25kn.txt txt: ./txt/cord-353957-0pjg25kn.txt summary: Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV infection can effectively restrict the virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV infection. Interestingly, we observed that ATMUV infection could trigger duck innate immune response including robust expression of particular type I and type III IFNs and IFITM family proteins. Our previous studies had shown that ATMUV infection effectively triggers the host innate immune response, including robust upregulation of type I and type III IFNs and some critical ISGs in chicken and CEF (Chen et al., 2016a) . To confirm these findings, DF-1 cell lines expressing specific shRNA targeting each of these IFITMs were infected with ATMUV and harvested at 36 hpi, followed by qRT-PCR assay to detect mRNA expression of viral genes. abstract: Avian Tembusu virus (ATMUV) is a highly pathogenic flavivirus that causes significant economic losses to the Chinese poultry industry. Our previous experiments demonstrated that ATMUV infection effectively triggered host innate immune response through MDA5 and TLR3-dependent signaling pathways. However, little information is available on the role of interferon-stimulated genes (ISGs) in defending against ATMUV infection. In this study, we found that ATMUV infection induced robust expression of type I and type III interferon (IFNs) in duck tissues. Furthermore, we observed that expression of interferon-inducible transmembrane proteins (IFITMs) was significantly upregulated in DEF and DF-1 cells after infection with ATMUV. Similar results were obtained from in vivo studies using ATMUV-infected ducklings. Importantly, we showed that knockdown of endogenous IFITM1 or IFITM3 by specific shRNA markedly enhanced ATMUV replication in DF-1 cells. However, disruption of IFITM2 expression had no obvious effect on the ATMUV replication. In addition, overexpression of chicken or duck IFITM1 and IFITM3 in DF-1 cells impaired the replication of ATMUV. Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV infection can effectively restrict the virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/28473814/ doi: 10.3389/fmicb.2017.00672 id: cord-326762-t89jtjmi author: Chen, Weiye title: Establishment of a stable CHO cell line with high level expression of recombinant porcine IFN-β date: 2011-06-30 words: 4042.0 sentences: 185.0 pages: flesch: 50.0 cache: ./cache/cord-326762-t89jtjmi.txt txt: ./txt/cord-326762-t89jtjmi.txt summary: title: Establishment of a stable CHO cell line with high level expression of recombinant porcine IFN-β Abstract A CHO cell clone (CHO-PoIFN-β) with stable porcine IFN-β expression under control of CMV promoter was selected under G418 pressure. The purpose of this study was to establish highly efficient and stable expression of recombinant porcine IFN-b in CHO-K1 cell line, and further characterize the biological activity of the product. In order to study the antiviral capacity of recombinant PoIFN-b against porcine viruses in vitro, PK15 cells were treated with 10-fold serially diluted PoIFN-b CHO (start from1.1  10 6 IU/ml) for 24 h, and then infected with 1000 TCID 50 of TGEV (Fig. 4A-C) or PRV (Fig. 4F-H) . The CHO-PoIFN-b cell line established in this study expresses the recombinant PoIFN-b that has the same biological function as natural porcine type I IFN. abstract: Abstract A CHO cell clone (CHO-PoIFN-β) with stable porcine IFN-β expression under control of CMV promoter was selected under G418 pressure. In a 25cm2 cell culture flask (5ml culture medium), the cumulative protein yield of recombinant PoIFN-β reached 2.3×106 IU/ml. This cells clone maintained stable expression for at least 20 generations even in the absence of G418 selection pressure. The expressed recombinant PoIFN-β could induce the expression of porcine Mx protein in PK15 cells, and activate the chicken Mx promoter-controlled luciferase reporter gene expression, confirming that the recombinant PoIFN-β has the biological activity of natural porcine type-I interferon. In addition, the recombinant PoIFN-β fully protected PK15 cells against 1000 TCID50 of porcine transmissible gastroenteritis virus and pseudo-rabies virus infection, demonstrating its high potential in therapeutic applications. This is the first report of establishing a mammalian cell line with stable expression of porcine IFN-β. url: https://www.sciencedirect.com/science/article/pii/S1043466610007738 doi: 10.1016/j.cyto.2010.12.002 id: cord-000409-lpf9lpky author: Chen, Yongwen title: Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection date: 2011-07-07 words: 5540.0 sentences: 296.0 pages: flesch: 49.0 cache: ./cache/cord-000409-lpf9lpky.txt txt: ./txt/cord-000409-lpf9lpky.txt summary: Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. In all, these results demonstrated that PD-1 deficiency led to enhanced pathological damage by MHV-3 in the liver, spleen, lymph node and thymus, where higher levels of PD-1-positive cells were found after infection. Results showed that the expression of FGL2 was principally associated with CD31-positive endothelial cells, CD68-positive macrophages and CD11c-positive DCs. Surprisingly, significantly higher levels of FGL2 were observed after infection in all of PD-1-deficient organs, including the liver, thymus, spleen, lymph nodes, and serum than that in those from WT littermates. However, the number of Foxp3-positive cells in the liver, spleen, lymph node or thymus was not significantly different between PD-1-deficient mice and their WT littermates after 72 h of MHV-3 infection (Fig. S3) . abstract: The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described. Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3). High levels of PD-1-positive CD4(+), CD8(+) T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection. PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates. As a result, more severe tissue damage was produced and mortality rates were higher. Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality. Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α. Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131267/ doi: 10.1371/journal.ppat.1001347 id: cord-337365-hugenn14 author: Chen, Zhuangzhuang title: The role of microglia in viral encephalitis: a review date: 2019-04-09 words: 7265.0 sentences: 391.0 pages: flesch: 38.0 cache: ./cache/cord-337365-hugenn14.txt txt: ./txt/cord-337365-hugenn14.txt summary: Microglia can exert a direct antiviral effect by producing type 1 interferon (IFN-1) to induce IFN-stimulated gene (ISG) expression of themselves or indirect antiviral effects by IFN-1 acting on other cells to activate corresponding signaling pathways. In a mouse model of West Nile virus (WNV) infection, it was found that the permeability of the BBB increased in mice lacking IFNAR, especially in the hindbrain, which leads to an increase in viral entry, indicating that IFNAR signaling has important regulatory effects on BBB permeability in this brain region. Loss of astrocyte IFNAR signaling pathway can cause a variety of consequences, including increased expression of inflammatory cytokines and chemokines, which disrupt the blood-brain barrier during neurotropic viral infection [30] . In a mouse model of lethal West Nile virus (WNV) infection, Peli1 promotes the production of pro-inflammatory cytokines and chemokines in microglia and promotes the entry of T cells and macrophages into the CNS. abstract: Viral encephalitis is still very prominent around the world, and traditional antiviral therapies still have shortcomings. Some patients cannot get effective relief or suffer from serious sequelae. At present, people are studying the role of the innate immune system in viral encephalitis. Microglia, as resident cells of the central nervous system (CNS), can respond quickly to various CNS injuries including trauma, ischemia, and infection and maintain the homeostasis of CNS, but this response is not always good; sometimes, it will exacerbate damage. Studies have shown that microglia also act as a double-edged sword during viral encephalitis. On the one hand, microglia can sense ATP signals through the purinergic receptor P2Y12 and are recruited around infected neurons to exert phagocytic activity. Microglia can exert a direct antiviral effect by producing type 1 interferon (IFN-1) to induce IFN-stimulated gene (ISG) expression of themselves or indirect antiviral effects by IFN-1 acting on other cells to activate corresponding signaling pathways. In addition, microglia can also exert an antiviral effect by inducing autophagy or secreting cytokines. On the other hand, microglia mediate presynaptic membrane damage in the hippocampus through complement, resulting in long-term memory impairment and cognitive dysfunction in patients with encephalitis. Microglia mediate fetal congenital malformations caused by Zika virus (ZIKV) infection. The gene expression profile of microglia in HIV encephalitis changes, and they tend to be a pro-inflammatory type. Microglia inhibited neuronal autophagy and aggravated the damage of CNS in HIV encephalitis; E3 ubiquitin ligase Pellino (pelia) expressed by microglia promotes the replication of virus in neurons. The interaction between amyloid-β peptide (Aβ) produced by neurons and activated microglia during viral infection is uncertain. Although neurons can mediate antiviral effects by activating receptor-interacting protein kinases 3 (RIPK3) in a death-independent pathway, the RIPK3 pathway of microglia is unknown. Different brain regions have different susceptibility to viruses, and the gene expression of microglia in different brain regions is specific. The relationship between the two needs to be further confirmed. How to properly regulate the function of microglia and make it exert more anti-inflammatory effects is our next research direction. url: https://doi.org/10.1186/s12974-019-1443-2 doi: 10.1186/s12974-019-1443-2 id: cord-327135-4c2flue4 author: Chinnaswamy, S title: Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections date: 2016-06-09 words: 9813.0 sentences: 499.0 pages: flesch: 48.0 cache: ./cache/cord-327135-4c2flue4.txt txt: ./txt/cord-327135-4c2flue4.txt summary: Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. Three independent groups conducted genome-wide association studies (GWASs) involving treatment response to chronic hepatitis C virus (HCV) infections, in three different geographical regions of the world, and reported that single-nucleotide polymorphisms (SNPs) in the IFNL locus (Figure 1 ), had strong association with treatment-induced HCV clearance irrespective of ethnicity and geographical location of the hosts. 49 In stark contrast, a dominant model of inheritance (of the non-beneficial IFNL SNP minor allele) has consistently given the best explanation on the observed phenotypes in association studies with both spontaneous clearance and IFN-based treatment response in chronic HCV infections. abstract: Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. This landmark discovery also brought renewed interest in type III IFN biology. After more than half a decade since this discovery, we now have reports that show that genetic association of IFNL gene polymorphisms in humans is not limited only to HCV infections but extends beyond, to include varied diseases such as non-alcoholic fatty liver disease, allergy and several other viral diseases including that caused by the human immunodeficiency virus. Notably, all these conditions have strong involvement of host innate immune responses. After the discovery of a deletion polymorphism that leads to the expression of a functional IFN-λ4 as the prime ‘functional’ variant, the relevance of other polymorphisms regulating the expression of IFN-λ3 is in doubt. Herein, I seek to critically address these issues and review the current literature to provide a framework to help further understanding of IFN-λ biology. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/gene.2016.24) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1038/gene.2016.24 doi: 10.1038/gene.2016.24 id: cord-023414-xxw5kptr author: Chistensen, H. R. title: Characterization of a Large Panel of Lactic Acid Bacteria Derived from the Human Gut for their Capacity to Polarize Dendritic Cell date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dendritic cells (DCs) are the principal stimulators of naïve T helper (Th) cells and play a pivotal regulatory role in the Th1, Th2 and Treg cell balance. DCs are present in the gut mucosa and may thus be target for modulation by gut microbes, including ingested probiotics. Here, we tested the hypothesis that species of lactic acid bacteria, important members of the gut flora, differentially activate DC. A large panel of human gut‐derived Lactobacillus and Bifidobacterium spp. was screened for DC‐polarizing capacity by exposing bone marrow‐derived murine DC to lethally irradiated bacteria. Cytokines in culture supernatants and DC‐surface maturation markers were analysed. Substantial differences were found among strains in the capacity to induce interleukin‐12 (IL‐12) and tumour necrosis factor (TNF)‐α, while the differences for IL‐10 and IL‐6 were less pronounced. Bifidobacteria tended to be weak IL‐12 and TNF‐α inducers, while both strong and weak IL‐12 inducers were found among the strains of Lactobacillus. Remarkably, strains weak in IL‐12 induction inhibited IL‐12 and TNF‐α production induced by an otherwise strong cytokine‐inducing strain of Lactobacillus casei, while IL‐10 production remained unaltered. Selected strains were tested for induction of DC maturation markers. Those lactobacilli with greatest capacity to induce IL‐12 were most effective in upregulating surface MHC class II and CD86. Moreover, L. casei‐induced upregulation of CD86 was reduced in the presence of a weak IL‐12‐inducing L. reuteri. In conclusion, human Lactobacillus and Bifidobacterium spp. polarize differentially DC maturation. Thus, the potential exists for Th1/Th2/Treg‐driving capacities of the gut DC to be modulated according to composition of gut flora including ingested probiotics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169554/ doi: 10.1111/j.0300-9475.2004.01423ap.x id: cord-345854-f0dq94j1 author: Chong, Wai Po title: The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome date: 2006-05-04 words: 1770.0 sentences: 116.0 pages: flesch: 54.0 cache: ./cache/cord-345854-f0dq94j1.txt txt: ./txt/cord-345854-f0dq94j1.txt summary: We examined whether polymorphisms of IFN-γ,TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). In this study, we hypothesized that the polymorphisms of the cytokine genes, i.e. IFN-γ +874A/T, TNF-α -308G/A, IL-10 -1082G/A and -592A/C, might be associated with SARS. We tested our hypotheses in 476 SARS patients and 449 healthy controls and found that polymorphism of IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner. The frequencies of genotypes and alleles of the 4 single nucleotide polymorphisms (SNPs) were compared between the SARS patients and healthy controls by 3 × 2 and 2 × 2 chi square test respectively. Our case-control study genotyped the 4 SNPs IFN-γ +874A/T, TNF-α -308G/A, IL-10 -1082G/A and -592A/C in 476 Chinese patients with SARS and 449 healthy controls. Association between mannose-binding lectin gene polymorphisms and susceptibility to severe acute respiratory syndrome coronavirus infection abstract: BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-γ,TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-γ,TNF-α and IL-10 for their associations with SARS. RESULTS: IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner (P < 0.001). Individuals with IFN-γ +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-α were not associated with SARS susceptibility. CONCLUSION: IFN-γ +874A allele was shown to be a risk factor in SARS susceptibility. url: https://www.ncbi.nlm.nih.gov/pubmed/16672072/ doi: 10.1186/1471-2334-6-82 id: cord-304553-gbwb7fqi author: Christopher, Mary E. title: Broad-Spectrum Drugs Against Viral Agents date: 2008-09-01 words: 11323.0 sentences: 550.0 pages: flesch: 40.0 cache: ./cache/cord-304553-gbwb7fqi.txt txt: ./txt/cord-304553-gbwb7fqi.txt summary: Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. Poly (ICLC), a dsRNA, and CpG ODNs, molecular mimics for TLR3 and TLR9, respectively, have been reported to non-specifically stimulate the innate immune system and to provide protection against various bacterial and viral pathogens, including influenza. Mice treated with two doses of poly (ICLC), 48 h apart, up to 12 d prior to viral challenge were completely protected from infection, whereas survival rates decreased to 80, 40 and 0%, when pre-treatment was given 14, 16 or 20 d prior to virus challenge, respectively [32] . CpG ODN treatment of splenocytes from senescence-accelerated SAM-P1 strain of mice increased IFN-γ and administration in vivo generated virus-specific cytotoxic T lymphocyte responses, NK cell activation, virus-specific Ig isotype switch from IgG1 to IgG2a, increased viral clearance and survival following influenza viral challenge. Viral infection and Toll-like receptor agonists induce a differential expression of type I and lambda interferons in human plasmacytoid and monocyte-derived dendritic cells abstract: Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance. url: https://doi.org/10.3390/ijms9091561 doi: 10.3390/ijms9091561 id: cord-311718-z64g8fce author: Chu, Yeonjeong title: Design, synthesis, and biological evaluation of N-arylpiperazine derivatives as interferon inducers date: 2020-10-16 words: 1967.0 sentences: 115.0 pages: flesch: 43.0 cache: ./cache/cord-311718-z64g8fce.txt txt: ./txt/cord-311718-z64g8fce.txt summary: Type I Interferon (IFN) signaling plays an important role in the immune defense system against virus infection and in the innate immune response, thus IFNs are widely used as anti-viral agents and treatment for immune disorder or cancer. We designed and synthesized a series of arylpiperazine derivatives as interferon inducers  We tested different linker system and carbonyl moiety resulted in increase of potency  5i exhibited the activity of interferon inducer with EC 50 of 13.1 μM and no cytotoxicity  5i initiated immune responses by mediating type I IFN signaling Based on these important characteristics of the ARP skeleton, we designed and synthesized a series of 2,3-dichloro ARP derivatives by further N-modification on piperazine part with different linker moiety such as thiourea, urea, and carbonyl functional group in order to assess structure-activity relationship (SAR; Figure 1b All the synthesized compounds were evaluated using ISRE reporter assay on THP-1 human monocyte cells for monitoring immune response. abstract: Type I Interferon (IFN) signaling plays an important role in the immune defense system against virus infection and in the innate immune response, thus IFNs are widely used as anti-viral agents and treatment for immune disorder or cancer. However, there is a growing demand for novel small-molecule IFN inducer due to tolerance, toxicity, or short duration of action following direct administration of IFNs. In this study, we assessed arylpiperazine (ARP) as a new core skeleton of IFN inducer. To investigate structure-activity relationship, we designed and synthesized a series of ARP analogues and evaluated the ability to stimulate IFN response in THP-1 human monocyte cells. Compound 5i was identified as a potent type I IFN inducer as it significantly increased cytokine secretion and increased expression of various IFN-stimulating genes which are representative biomarkers of type I IFN pathway. Our results suggested a beneficial therapeutic potential of 5i as an anti-viral agent. url: https://doi.org/10.1016/j.bmcl.2020.127613 doi: 10.1016/j.bmcl.2020.127613 id: cord-300319-9k8zseao author: Cinatl Jr., J. title: Infection of cultured intestinal epithelial cells with severe acute respiratory syndrome coronavirus date: 2004 words: 3017.0 sentences: 159.0 pages: flesch: 42.0 cache: ./cache/cord-300319-9k8zseao.txt txt: ./txt/cord-300319-9k8zseao.txt summary: To identify a model for the study of intestinal pathogenesis of severe acute respiratory syndrome (SARS) we tested the sensitivity of six human intestinal epithelial cell lines to infection with SARS coronavirus (SARS-CoV). In both cell lines, SARS-CoV infection deregulated expression of cellular genes which may be important for the intestinal pathogenesis of SARS. To investigate whether ACE2 is a functional receptor for SARS-CoV in intestinal epithelial cell cultures, the cells were pre-treated for 60 min at 37°C with goat antibody directed against the human ACE2 ectodomain (R&D Systems; Wiesbaden-Nordenstadt, Germany). SARS-CoV infection of Caco-2 cells up-regulated OAS2 and MXA but not PKR genes. The discrepancy between transcriptional activation of IFN-induced genes and the ability of SARS-CoV to replicate in Caco-2 cells could be explained by the existence of a specific viral mechanism for escaping IFNinduced anti-viral effects common to most viruses [28] . This justifies the use of intestinal cell lines as a model to study the direct effects of SARS-CoV infection on gene expression in permissive human cells. abstract: To identify a model for the study of intestinal pathogenesis of severe acute respiratory syndrome (SARS) we tested the sensitivity of six human intestinal epithelial cell lines to infection with SARS coronavirus (SARS-CoV). In permissive cell lines, effects of SARS-CoV on cellular gene expression were analysed using high-density oligonucleotide arrays. Caco-2 and CL-14 cell lines were found to be highly permissive to SARS-CoV, due to the presence of angiotensin-converting enzyme 2 as a functional receptor. In both cell lines, SARS-CoV infection deregulated expression of cellular genes which may be important for the intestinal pathogenesis of SARS. url: https://www.ncbi.nlm.nih.gov/pubmed/15316659/ doi: 10.1007/s00018-004-4222-9 id: cord-315328-8g40ukml author: Clementi, Nicola title: Interferon-β-1a Inhibition of Severe Acute Respiratory Syndrome–Coronavirus 2 In Vitro When Administered After Virus Infection date: 2020-06-19 words: 2275.0 sentences: 115.0 pages: flesch: 50.0 cache: ./cache/cord-315328-8g40ukml.txt txt: ./txt/cord-315328-8g40ukml.txt summary: In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection. In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection. In the current study, we assessed its anti-SARS-CoV-2 activity in vitro to give a preclinical background to clinical trials evaluating the possible therapeutic role of IFN-β-1a in patients with coronavirus disease 2019 (COVID-19). Vero E6 cells were treated with concentrations ranging from 5000 to 0.01 IU/mL of IFN-β-1a 1 hour after inoculation with SARS-CoV-2 and monitored for cytopathic effect and real-time-PCR quantitative evaluation at 48, 72, and 96 hours after infection. Our in vitro observations shed light for the first time on that antiviral activity of IFN-β-1a against SARS-CoV-2 when administered after the infection of cells, highlighting its possible efficacy in an early therapeutic setting. abstract: The ongoing coronavirus disease 2019 pandemic has forced the clinical and scientific community to try drug repurposing of existing antiviral agents as a quick option against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Under this scenario, interferon (IFN) β-1a, whose antiviral potential is already known, and which is a drug currently used in the clinical management of multiple sclerosis, may represent as a potential candidate. In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection. url: https://www.ncbi.nlm.nih.gov/pubmed/32559285/ doi: 10.1093/infdis/jiaa350 id: cord-303189-ktl4jw8v author: Coccia, Eliana M. title: Early IFN type I response: Learning from microbial evasion strategies date: 2015-03-31 words: 15202.0 sentences: 738.0 pages: flesch: 40.0 cache: ./cache/cord-303189-ktl4jw8v.txt txt: ./txt/cord-303189-ktl4jw8v.txt summary: Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. In these cells, the HCV-induced miR-21 has been recently reported to be involved in evasion of IFN-I production and stimulation of HCV replication, upon suppression of MyD88 and IRAK1 expression, that is required for the TLR7-mediated sensing of the virus [100] . Amongst RNA viruses that, as HCV, can establish a persistent infection, HIV-1, a lentivirus from the Retroviridae family, represents a paradigm for its ability to prevent or circumvent the innate immune response mediated by IFN-I. Overall, viruses as HCV and HIV-1 have evolved nifty strategies to dampen the host innate response in cells where a productive infection may take place, while they induce infection-independent mechanisms in non-permissive cells to facilitate the viral life cycle and promote a chronic inflammation. abstract: Abstract Type I interferon (IFN) comprises a class of cytokines first discovered more than 50 years ago and initially characterized for their ability to interfere with viral replication and restrict locally viral propagation. As such, their induction downstream of germ-line encoded pattern recognition receptors (PRRs) upon recognition of pathogen-associated molecular patterns (PAMPs) is a hallmark of the host antiviral response. The acknowledgment that several PAMPs, not just of viral origin, may induce IFN, pinpoints at these molecules as a first line of host defense against a number of invading pathogens. Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. On the other hand an inverse interference to escape the IFN system is largely exploited by pathogens through a number of tactics and tricks aimed at evading, inhibiting or manipulating the IFN pathway, that result in progression of infection or establishment of chronic disease. In this review we discuss the interplay between the IFN system and some selected clinically important and challenging viruses and bacteria, highlighting the wide array of pathogen-triggered molecular mechanisms involved in evasion strategies. url: https://doi.org/10.1016/j.smim.2015.03.005 doi: 10.1016/j.smim.2015.03.005 id: cord-002201-pnw5ytj4 author: Corredor, Juan C title: N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells date: 2016-03-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: N-myc oncogene amplification is associated but not present in all cases of high-risk neuroblastoma (NB). Since oncogene expression could often modulate sensitivity to oncolytic viruses, we wanted to examine if N-myc expression status would determine virotherapy efficacy to high-risk NB. We showed that induction of exogenous N-myc in a non-N-myc-amplified cell line background (TET-21N) increased susceptibility to oncolytic vesicular stomatitis virus (mutant VSVΔM51) and alleviated the type I IFN-induced antiviral state. Cells with basal N-myc, on the other hand, were less susceptible to virus-induced oncolysis and established a robust IFN-mediated antiviral state. The same effects were also observed in NB cell lines with and without N-myc amplification. Microarray analysis showed that N-myc overexpression in TET-21N cells downregulated IFN-stimulated genes (ISGs) with known antiviral functions. Furthermore, virus infection caused significant changes in global gene expression in TET-21N cells overexpressing N-myc. Such changes involved ISGs with various functions. Therefore, the present study showed that augmented susceptibility to VSVΔM51 by N-myc at least involves downregulation of ISGs with antiviral functions and alleviation of the IFN-stimulated antiviral state. Our studies suggest the potential utility of N-myc amplification/overexpression as a predictive biomarker of virotherapy response for high-risk NB using IFN-sensitive oncolytic viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008254/ doi: 10.1038/mto.2016.5 id: cord-292593-apdyaujt author: Coulter-Mackie, Marion title: In vivo and in vitro models of demyelinating diseases XII. Persistence and expression of corona JHM vims functions in RN2-2 Schwannoma cells during latency date: 1985-10-31 words: 5832.0 sentences: 299.0 pages: flesch: 55.0 cache: ./cache/cord-292593-apdyaujt.txt txt: ./txt/cord-292593-apdyaujt.txt summary: Interference with vesicular stomatitis virus (VSV) production by JHMV was tested in persistently or latently infected RN-2 cells using as the controls, uninfected RN2-2 cells. Since upon infection of RN2-2 cultures with JHMV at 39.5"C and maintenance in a state of latency at that temperature for several days, the cells commenced yielding pfu upon shift down to 32.5"C (Lucas et al., 1978) , these data suggest that penetration and eclipse of the virus inoculum must have occurred normally at 39.5"C and restriction most probably developed at a subsequent stage. It is very significant that during incubation at the restrictive temperature for as long as 7 days and beyond, when RN2-2 cells had multiplied through 6-7 generations, the 56K antigen was readily detectable (channel I), implying that during latency, in the absence of infectious virus production, translation into JHMV nucleocapsid protein continued. abstract: Abstract The coronavirus JHMV persistently infects rat Schwannoma cells RN2-2 at 32.5°C and enters a host-imposed reversible, latent state at 39.5°C. JHMV can remain up to 20 days in the latent state and about 14 days before the cultures lose the capacity to resume virus production upon return to 32.5°C. Although persistently and latently infected RN2-2 cells display resistance to superinfection by a heterologous agent VSV, these cells do not release detectable soluble mediators (e.g., interferon) of the antiviral state. Nevertheless, RN2-2 cells are competent to synthesize and release interferon when treated with the appropriate inducers. These observations suggest that interferon does not play any role or may not be the major factor in the control of latency in the Schwannoma cell. Hybridization with virus-specific cDNAs shows that all viral mRNAs are present during latency and that viral mRNAs are present in the polysomes of infected cells at 39.5°C. Western immunoblotting with hybridoma antibodies demonstrates that viral specific proteins are produced at the restrictive temperature. These results url: https://api.elsevier.com/content/article/pii/0168170285900498 doi: 10.1016/0168-1702(85)90049-8 id: cord-304330-egvdvvtx author: Damsky, William title: When interferon tiptoes through COVID-19: Pernio-like lesions and their prognostic implications during SARS-CoV-2 infection date: 2020-06-19 words: 442.0 sentences: 32.0 pages: flesch: 56.0 cache: ./cache/cord-304330-egvdvvtx.txt txt: ./txt/cord-304330-egvdvvtx.txt summary: William Damsky MD, PhD 1,* , Danielle Peterson MD 1 Brett King MD, PhD 1,* 4 5 has suggested that SARS-CoV-2 infection is sometimes characterized by a muted anti-40 viral Type I and III interferon (IFN) response, 6,7 which may explain progression to 41 severe clinical manifestations in some patients; a robust Type I IFN response was 42 associated with rapid viral clearance and bland disease course. Together, these data suggest that COVID toes may be a 46 marker of patients that are able to mount a robust anti-viral immune response to SARS-CoV-2 and prognosticate a milder course of COVID-19. 6,7 Therefore, we hypothesize that pernio-like lesions, which can 81 occur with elevated Type I IFN signaling, are the result of a robust anti-viral response in patients with COVID-19, and, therefore, are associated with a favorable disease course, 83 as observed in these patients. Pernio-like skin lesions associated 101 with COVID-19: a case series of 318 patients from 8 countries abstract: nan url: https://api.elsevier.com/content/article/pii/S0190962220311506 doi: 10.1016/j.jaad.2020.06.052 id: cord-103675-21qu87oh author: Dandekar, Ajai A. title: Bystander CD8 T-Cell-Mediated Demyelination is Interferon-γ-Dependent in a Coronavirus Model of Multiple Sclerosis date: 2004-02-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Mice infected with the coronavirus mouse hepatitis virus, strain JHM (JHM) develop a disease that shares many histological characteristics with multiple sclerosis. We previously demonstrated that JHM-infected mice that only have CD8 T cells specific for an epitope not in the virus develop demyelination on specific activation of these cells. Herein we show that this process of bystander T-cell-mediated demyelination is interferon-γ (IFN-γ)-dependent. The absence of IFN-γ abrogated demyelination but did not change T-cell infiltration or expression levels of inflammatory cytokines or chemokines in the spinal cord. These results are consistent with models in which IFN-γ contributes to CD8 T-cell-mediated demyelination by activation of macrophages/microglia, the final effector cells in the disease process. url: https://api.elsevier.com/content/article/pii/S0002944010631264 doi: 10.1016/s0002-9440(10)63126-4 id: cord-317333-unrd76bo author: Danesh, Ali title: Early gene expression events in ferrets in response to SARS coronavirus infection versus direct interferon-alpha2b stimulation date: 2011-01-05 words: 5467.0 sentences: 278.0 pages: flesch: 48.0 cache: ./cache/cord-317333-unrd76bo.txt txt: ./txt/cord-317333-unrd76bo.txt summary: Evaluation of gene expression patterns in PBMCs and lung necropsies of SARS-CoV-infected ferrets led us to the identification of 7 upregulated IRGs that also were upregulated in response to IFN-α2b injection. Since STAT1 was phosphorylated following SARS-CoV infection and IFN-α2b injection, we investigated select IRG expression by qRT-PCR following in vitro stimulation of ferret peripheral whole blood with IFN-α2b. These gene expression and STAT1 phosphorylation findings suggested that robust IFN responses were activated following SARS-CoV infection 2 days post-infection. The comparison of microarray results between the lung tissue of IFN-α2b and SARS-CoV ferrets at day 1 revealed commonalities in the expression patterns of most IRGs. STAT1, MX1, OAS1, OAS2, ISG15, IFI44, IFI44L and EIF2AK2 were among the overlapping genes (Fig. 3B ). Analysis of the IFN signaling canonical pathway showed the upregulation of STAT1, MX1, OAS1, OAS2, ISG15 and IFI44 in lung necropsies of IFN-α2b injected and SARS-CoV infected ferrets (Fig. 4) . abstract: Type I interferons (IFNs) are essential to the clearance of viral diseases, however, a clear distinction between genes upregulated by direct virus–cell interactions and genes upregulated by secondary IFN production has not been made. Here, we investigated differential gene regulation in ferrets upon subcutaneous administration of IFN-α2b and during SARS-CoV infection. In vivo experiments revealed that IFN-α2b causes STAT1 phosphorylation and upregulation of abundant IFN response genes (IRGs), chemokine receptors, and other genes that participate in phagocytosis and leukocyte transendothelial migration. During infection with SARS-CoV not only a variety of IRGs were upregulated, but also a significantly broader range of genes involved in cell migration and inflammation. This work allowed dissection of several molecular signatures present during SARS-CoV which are part of a robust IFN antiviral response. These signatures can be useful markers to evaluate the status of IFN responses during a viral infection and specific features of different viruses. url: https://www.sciencedirect.com/science/article/pii/S0042682210006380 doi: 10.1016/j.virol.2010.10.002 id: cord-002630-5616n73p author: Dargahi, Narges title: Multiple Sclerosis: Immunopathology and Treatment Update date: 2017-07-07 words: 11316.0 sentences: 561.0 pages: flesch: 47.0 cache: ./cache/cord-002630-5616n73p.txt txt: ./txt/cord-002630-5616n73p.txt summary: We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS. Based on Phase III human clinical trials in patients with RRMS (TRANSFORMS, FREEDOMS and FREEDOMS II), fingolimod was more effective compared to first line treatment IFNβ-1a and placebo, in reducing the frequency of flare-ups (clinical exacerbations), disability progression, MRI outcome measures, including brain volume loss and was associated with clearly identified adverse events [103, 136, 137] . Citrullination of linear and cyclic altered peptide ligands from myelin basic protein (mbp(87-99)) epitope elicits a th1 polarized response by t cells isolated from multiple sclerosis patients: Implications in triggering disease abstract: The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532591/ doi: 10.3390/brainsci7070078 id: cord-305959-x061q8t7 author: Davoudi-Monfared, Effat title: A Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of Severe COVID-19 date: 2020-08-20 words: 4733.0 sentences: 280.0 pages: flesch: 50.0 cache: ./cache/cord-305959-x061q8t7.txt txt: ./txt/cord-305959-x061q8t7.txt summary: As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively, P = 0.95). The vital signs at the time of hospital admission were not statistically different, except respiratory rate was significantly higher in the IFN group (22 versus 20, respectively, P ϭ 0.009). As a primary outcome, the time to clinical response was not significantly different between the IFN and control groups (9.7 Ϯ 5.8 versus 8.3 Ϯ 4.9 days, respectively, P ϭ 0.95), which is shown in the Kaplan-Meier plot (Fig. 2) . On day 0, there was no significant difference between the groups in terms of the components Interferon ␤-1a in Treatment of Severe COVID19 Antimicrobial Agents and Chemotherapy of this scale. The present study was the first randomized, open-label, controlled trial that assessed the efficacy and safety of IFN ␤-1a in the treatment of patients diagnosed with severe COVID-19. abstract: To the best of our knowledge, there is no published study on the use of interferon β-1a (IFN β-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN β-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN β-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir). Each 44-μg/ml (12 million IU/ml) dose of interferon β-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted of 39 patients who received only the national protocol medications. The primary outcome of the study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of intensive care unit stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects, and complications during the hospitalization. Between 29 February and 3 April 2020, 92 patients were recruited, and a total of 42 patients in the IFN group and 39 patients in the control group completed the study. As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively, P = 0.95). On day 14, 66.7% versus 43.6% of patients in the IFN group and the control group, respectively, were discharged (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.05 to 6.37). The 28-day overall mortality was significantly lower in the IFN than the control group (19% versus 43.6%, respectively, P = 0.015). Early administration significantly reduced mortality (OR, 13.5; 95% CI, 1.5 to 118). Although IFN did not change the time to reach the clinical response, adding it to the national protocol significantly increased discharge rate on day 14 and decreased 28-day mortality. (This study is in the Iranian Registry of Clinical Trials under identifier IRCT20100228003449N28.) url: https://doi.org/10.1128/aac.01061-20 doi: 10.1128/aac.01061-20 id: cord-254747-vox5xsgd author: Deng, Xufang title: An “Old” Protein with A New Story: Coronavirus Endoribonuclease Is Important for Evading Host Antiviral Defenses date: 2018-04-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Here we review the evolving story of the coronavirus endoribonuclease (EndoU). Coronavirus EndoU is encoded within the sequence of nonstructural protein (nsp) 15, which was initially identified as a component of the viral replication complex. Biochemical and structural studies revealed the enzymatic nature of nsp15/EndoU, which was postulated to be essential for the unique replication cycle of viruses in the order Nidovirales. However, the role of nsp15 in coronavirus replication was enigmatic as EndoU-deficient coronaviruses were viable and replicated to near wild-type virus levels in fibroblast cells. A breakthrough in our understanding of the role of EndoU was revealed in recent studies, which showed that EndoU mediates the evasion of viral double-stranded RNA recognition by host sensors in macrophages. This new discovery of nsp15/EndoU function leads to new opportunities for investigating how a viral EndoU contributes to pathogenesis and exploiting this enzyme for therapeutics and vaccine design against pathogenic coronaviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/29307596/ doi: 10.1016/j.virol.2017.12.024 id: cord-264121-4801f4o4 author: Dhariwal, Jaideep title: Anti-viral agents: potential utility in exacerbations of asthma date: 2013-05-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Asthma is the most common chronic respiratory disease and its prevalence is on the increase. Respiratory viral infections in early life have been suggested to increase the risk of development of asthma in later life and virus infection remains the single greatest precipitant of asthma exacerbations. The development of effective anti-viral treatments remains a key target for therapeutic intervention. Here we discuss the role of respiratory viral infection in asthma exacerbation and highlight current and potential anti-viral agents and their mechanisms of action. url: https://www.ncbi.nlm.nih.gov/pubmed/23664758/ doi: 10.1016/j.coph.2013.04.010 id: cord-333463-u7je0d1o author: Diaz-Salazar, Carlos title: Natural killer cell responses to emerging viruses of zoonotic origin date: 2020-08-09 words: 6193.0 sentences: 353.0 pages: flesch: 43.0 cache: ./cache/cord-333463-u7je0d1o.txt txt: ./txt/cord-333463-u7je0d1o.txt summary: Nearly all emerging viruses, including Ebola, Dengue, Nipah, West Nile, Zika, and coronaviruses (including SARS-Cov2, the causative agent of the current COVID-19 pandemic), have zoonotic origins, indicating that animal-to-human transmission constitutes a primary mode of acquisition of novel infectious diseases. Natural killer (NK) cells are innate lymphocytes that play a critical role in the early antiviral response, secreting effector cytokines and clearing infected cells. This review describes the role of Natural killer (NK) cells, a critical component of early antiviral immunity, in the establishment of tolerance to viral infections in natural hosts, as well as their role in the development of disease in nonnatural hosts. Altogether, it is believed that quick control of viral infections and reduced induction of pro-inflammatory cytokines have allowed bat viruses to rapidly co-evolve with their host without provoking major immuneThe careful study of the immune system in reservoirs of zoonotic diseases will certainly offer insights into how these animals carry high viral loads while remaining asymptomatic. abstract: Emerging viral diseases pose a major threat to public health worldwide. Nearly all emerging viruses, including Ebola, Dengue, Nipah, West Nile, Zika, and coronaviruses (including SARS-Cov2, the causative agent of the current COVID-19 pandemic), have zoonotic origins, indicating that animal-to-human transmission constitutes a primary mode of acquisition of novel infectious diseases. Why these viruses can cause profound pathologies in humans, while natural reservoir hosts often show little evidence of disease is not completely understood. Differences in the host immune response, especially within the innate compartment, have been suggested to be involved in this divergence. Natural killer (NK) cells are innate lymphocytes that play a critical role in the early antiviral response, secreting effector cytokines and clearing infected cells. In this review, we will discuss the mechanisms through which NK cells interact with viruses, their contribution towards maintaining equilibrium between the virus and its natural host, and their role in disease progression in humans and other non-natural hosts. url: https://www.ncbi.nlm.nih.gov/pubmed/32784125/ doi: 10.1016/j.coviro.2020.07.003 id: cord-309619-glb2y82u author: Domingo, Pere title: The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19) date: 2020-07-29 words: 9353.0 sentences: 508.0 pages: flesch: 40.0 cache: ./cache/cord-309619-glb2y82u.txt txt: ./txt/cord-309619-glb2y82u.txt summary: Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1–7)/Mas1R axis. SARS-CoV induces the signal transducer and activator of transcription 1 TACE TNF-a converting enzyme TBK1 TANK-binding kinase 1 TLR toll-like receptor TMPRSS2 type II transmembrane serine protease TNF-a tumor necrosis alpha TRAF3 TNF receptor-associated factor 3 XCR1 XCL1 (Chemokine [C motif] ligand 1) and XCL3 (Chemokine [C motif] ligand 3) receptor production of double-membrane vesicles that lack PRRs and can then replicate in these vesicles [18] . COVID-19 patients have high serum levels of inflammatory cytokines, including interleukin (IL)-2, IL-7, IL-10, granulocyte-colony stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage SARS-CoV-2 infects primarily type II pneumocytes through binding to the ACE2 receptor. ACE2 = Angiotensin-converting enzyme 2; SARS-CoV-2 = Severe acute respiratory syndrome coronavirus 2; Ang II = Angiotensin II; ROS = Reactive oxygen species; AT1R = Angiotensin 1 receptor; ADAM17 = A disintegrin and metalloproteinase domain 17; TNF-a = Tumor necrosis factor alpha; TMPRSS2 = transmembrane protease serine 2. abstract: The pathogenesis of coronavirus disease 2019 (COVID-19) may be envisaged as the dynamic interaction between four vicious feedback loops chained or happening at once. These are the viral loop, the hyperinflammatory loop, the non-canonical renin-angiotensin system (RAS) axis loop, and the hypercoagulation loop. Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1–7)/Mas1R axis. The viral feedback loop includes evading the host's innate response, uncontrolled viral replication, and turning on a hyperactive adaptative immune response. The inflammatory loop is composed of the exuberant inflammatory response feeding back until exploding in an actual cytokine storm. Downregulation of the ACE2/Ang-(1–7)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS. The coagulation loop is a hypercoagulable state caused by the interplay between inflammation and coagulation in an endless feedback loop. The result is a hyperinflammatory and hypercoagulable state producing acute immune-mediated lung injury and eventually, adult respiratory distress syndrome. url: https://doi.org/10.1016/j.ebiom.2020.102887 doi: 10.1016/j.ebiom.2020.102887 id: cord-260291-zfpcuhpy author: Doménech, Ana title: Use of recombinant interferon omega in feline retrovirosis: From theory to practice date: 2011-10-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Type-I interferons (IFNs) are cytokines that have non-specific antiviral activity, participating mostly in innate defense mechanisms. Their administration has been proposed to treat several viral and immunomediated diseases as an immunomodulatory therapy. Due to its availability, recombinant human interferon-alpha (rHuIFN-α) has been studied in relation to feline retrovirosis, both in vitro and in vivo. However, IFNs are species-specific and antibodies have been shown to develop in response to the high rHuIFN-α doses necessary for an effective therapy. A recombinant feline IFN has been developed, which has been characterized as interferon-omega (rFeIFN-ω), designed to overcome these problems. Nonetheless, very few studies have been undertaken to evaluate its efficacy in cats naturally infected with FIV or FeLV. In an initial study, we here demonstrated that rFeIFN-ω can dramatically improve the clinical condition of infected cats, and induce improvement of hematologic parameters. Minor changes or no change was observed for hypergammaglobulinemia, CD4/CD8 ratio, proviral load, viremia and RT activity, suggesting that the overall effect of IFN was on innate immunity. More studies are needed in order to better understand its in vivo mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/21719116/ doi: 10.1016/j.vetimm.2011.06.008 id: cord-272117-erzpz3c0 author: Downey, Jeffrey title: Dissecting host cell death programs in the pathogenesis of influenza date: 2018-04-18 words: 9230.0 sentences: 440.0 pages: flesch: 33.0 cache: ./cache/cord-272117-erzpz3c0.txt txt: ./txt/cord-272117-erzpz3c0.txt summary: Experimentally, apoptosis of IAV-infected epithelial cells was shown to be dependent upon viral replication, as an inactivated virus failed to induce apoptosis in mice [46] and human cells [47] . PKR can directly sense dsRNA generated during viral replication to induce Fas expression and FADD-dependent apoptosis [52] , as well as inhibit host and viral protein translation through the phosphorylation of eIF2a [53] in IAV-infected cells [54] . Additionally, pandemic and highly virulent strains of the virus, including HPAI and the 1918 H1N1 strain, are known to completely exhaust the replicative niche of epithelial cells of the lung over the course of infection as a by-product of overly exuberant replication and failure of immune response to control viral propagation. Collectively, these findings suggest that in contrast to the biphasic role of epithelial cell apoptosis in preventing or promoting pathogenesis, highly virulent IAV rapidly infects and induces early death in pulmonary M4 to suppress antiviral responses. abstract: Influenza A virus (IAV) is a pulmonary pathogen, responsible for significant yearly morbidity and mortality. Due to the absence of highly effective antiviral therapies and vaccine, as well as the constant threat of an emerging pandemic strain, there is considerable need to better understand the host–pathogen interactions and the factors that dictate a protective versus detrimental immune response to IAV. Even though evidence of IAV-induced cell death in human pulmonary epithelial and immune cells has been observed for almost a century, very little is known about the consequences of cell death on viral pathogenesis. Recent study indicates that both the type of cell death program and its kinetics have major implications on host defense and survival. In this review, we discuss advances in our understanding of cell death programs during influenza virus infection, in hopes of fostering new areas of investigation for targeted clinical intervention. url: https://api.elsevier.com/content/article/pii/S1286457918300935 doi: 10.1016/j.micinf.2018.03.005 id: cord-023441-q83y12sk author: Draborg, H. title: Recominant Expression and Immunological Characterization of House Dust Mite Allergen Der P 1 date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The cysteine protease Der p1 from dust mite of the genus Dermatophagoides pteronyssinus is a major type I allergen. About 80% of house dust mite (HDM) allergic individuals are reactive to this protease in standard assays for detection of IgE. A curative treatment for atopic allergy is immunotherapy (IT) with HDM extracts which are complex mixtures occasionally resulting in anaphylactic reactions. Novozymes focuses on developing a recombinant variant of Der p1 which exhibit lowered risk of IgE‐mediated allergic reactions, while maintaining its ability to trigger proper Th‐cell responses. This may provide a safer alternative for specific IT of HDM allergy. A secreted recombinant form of pro‐Der p 1 expressed by Saccharamyces cerevisiae was obtained by fusion of the pro‐enzyme to a fungal signal peptide. The N‐glycosylation site of Der p1 was mutated resulting in a deglycosylated pro‐enzyme with a molecular mass of 35 kDa. Protein purification procedure was developed to obtain nearly pure Der p1 protein followed by determination of concentration by active‐site‐titration with the cysteine protease inhibitor E64. The deglycosylated recombinant pro‐Der p 1 revealed immunologic similarity to the native Der p 1 molecule when compared in basophile histamine release, IgE‐binding assays and T‐cell proliferation assays. By in silico epitope mapping of a modelled 3‐dimensional structure of Der p1, five putative IgG and IgE epitopes were predicted. By protein engineering, the predicted epitopes were removed one by one in Der p1 and screening for hypoallergenic variants was performed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169606/ doi: 10.1111/j.0300-9475.2004.01423ag.x id: cord-252528-rgnhfcbx author: Du, Fenghe title: COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness date: 2020-07-16 words: 8437.0 sentences: 359.0 pages: flesch: 30.0 cache: ./cache/cord-252528-rgnhfcbx.txt txt: ./txt/cord-252528-rgnhfcbx.txt summary: • Anti-inflammatory therapies, including tocilizumab, chloroquine, and hydroxychloroquine, which can be promising treatment to control excessive cytokine release in severe COVID-19, have the potential to reduce the risk of vascular thrombotic events, but more clinical data are needed for optimum instruction of drug use and drug selection. By interpreting the pathological mechanisms, we aim to illustrate that excessive pro-inflammatory cytokine release and potential ACE2 down-regulation can promote the hypercoagulable state in severe COVID19 , and propose that the anti-inflammatory medications, as well as ACEI/ARB, can benefit severe COVID-19 patients by reducing the risk of vascular thrombotic events. abstract: [Image: see text] url: https://doi.org/10.1007/s11239-020-02224-2 doi: 10.1007/s11239-020-02224-2 id: cord-001273-plz1ja2e author: Dussurget, Olivier title: The bacterial pathogen Listeria monocytogenes and the interferon family: type I, type II and type III interferons date: 2014-04-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Interferons (IFNs) are secreted proteins of the cytokine family that regulate innate and adaptive immune responses to infection. Although the importance of IFNs in the antiviral response has long been appreciated, their role in bacterial infections is more complex and is currently a major focus of investigation. This review summarizes our current knowledge of the role of these cytokines in host defense against the bacterial pathogen Listeria monocytogenes and highlights recent discoveries on the molecular mechanisms evolved by this intracellular bacterium to subvert IFN responses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009421/ doi: 10.3389/fcimb.2014.00050 id: cord-003855-so8xl199 author: Ebert, Gregor title: Virology Downunder, a meeting commentary from the 2019 Lorne Infection and Immunity Conference, Australia date: 2019-09-02 words: 1899.0 sentences: 95.0 pages: flesch: 39.0 cache: ./cache/cord-003855-so8xl199.txt txt: ./txt/cord-003855-so8xl199.txt summary: The bat innate immune response appears to be ''pre-activated'' with higher basal levels of type I interferon expression, in contrast to humans, who are very quick responders to viral infections, but require a lot more dampening of their immune signals afterwards to get back to basal levels. demonstrated that bats'' response to stress in form of viral infections is more targeted and thus potentially more effective by numerous adaptions and modifications of the innate immune system. In the ''Pathogenesis and Prevention of Infection'' session, Rosa Coldbeck-Shackley working with Michael Beard at the University of Adelaide, Australia, and also colleagues at the Hudson Institute, presented findings on the importance of interferon-epsilon (IFN-ɛ) in the innate immune response to ZIKV infection. Also in the ''Pathogenesis and Prevention of Infection'' session, Allison Abendroth (University of Sydney) presented ''Disarming the killer: targeting of natural killer cells by varicella zoster virus''. abstract: The aim of this article is to summarise the virology content presented at the 9th Lorne Infection and Immunity Conference, Australia, in February 2019. The broad program included virology as a key theme, and the commentary herein highlights several key virology presentations at the meeting. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720860/ doi: 10.1186/s12985-019-1217-6 id: cord-254895-ym0jsir5 author: Eisenächer, Katharina title: The role of viral nucleic acid recognition in dendritic cells for innate and adaptive antiviral immunity date: 2008-01-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Dendritic cells which are located at the interface of innate and adaptive immunity are targets for infection by many different DNA and RNA viruses. Dendritic cell subpopulations express specific nucleic acid recognition receptors belonging to the Toll-like receptor family (TLR3, 7, 8, 9) and the cytosolic RNA helicase family (RIG-I, MDA5, LGP2). Activation of dendritic cells by viral DNA and RNA via these receptors is essential for triggering the innate antiviral immune response and shaping the ensuing adaptive antiviral immunity. This review will summarize our current knowledge of viral nucleic acid recognition and signaling by Toll-like receptors and RNA helicases focusing on recent evidence for their specific functions in antiviral defense in vivo. url: https://www.ncbi.nlm.nih.gov/pubmed/18086372/ doi: 10.1016/j.imbio.2007.09.007 id: cord-336510-qzm9wgde author: Ellermann-Eriksen, Svend title: Macrophages and cytokines in the early defence against herpes simplex virus date: 2005-08-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone. Rather, an alliance of cytokines, macrophages and other cells seems to play a central role. Implications of this for future treatment modalities are shortly considered. url: https://www.ncbi.nlm.nih.gov/pubmed/16076403/ doi: 10.1186/1743-422x-2-59 id: cord-265941-eff4le0g author: Eng, Vik Ven title: The diverse roles of RIP kinases in host-pathogen interactions date: 2020-08-26 words: 11836.0 sentences: 657.0 pages: flesch: 34.0 cache: ./cache/cord-265941-eff4le0g.txt txt: ./txt/cord-265941-eff4le0g.txt summary: Nevertheless, the signal transduction that follows pathogen recognition elicits numerous defence mechanisms, including the induction of inflammatory cytokine, chemokine and interferon production, activation of programmed cell death pathways, and inevitably an adaptive immune response, all of which contribute to pathogen control and elimination [1] . As inhibition of necroptosis does not affect IAV control, while Mlkl-/-Fadd-/-mice exhibit marked susceptibility to IAV-induced lethality [78] , it signifies that RIPK1/3-mediated apoptosis is a major form of host protection against IAV infection. A number of studies have used purified pathogen components such as LPS to investigate the outcomes of RIPK1/3-mediated inflammasome signaling, which appear to be largely dependent on cell type, stimulus, and the availability or functional activity of certain host signaling proteins [65, [123] [124] [125] [126] [127] . Overall this suggests that RIPK2 plays an important role in both innate and adaptive immunity to infection [137, 151] , and that RIPK2 was mediating these responses via NOD1/2 and not directly via TLR activation [140] . abstract: Receptor Interacting Protein Kinases (RIPKs) are cellular signaling molecules that are critical for homeostatic signaling in both communicable and non-communicable disease processes. In particular, RIPK1, RIPK2, RIPK3 and RIPK7 have emerged as key mediators of intracellular signal transduction including inflammation, autophagy and programmed cell death, and are thus essential for the early control of many diverse pathogenic organisms. In this review, we discuss the role of each RIPK in host responses to bacterial and viral pathogens, with a focus on studies that have used pathogen infection models rather than artificial stimulation with purified pathogen associated molecular patterns. We also discuss the intricate mechanisms of host evasion by pathogens that specifically target RIPKs for inactivation, and finally, we will touch on the controversial issue of drug development for kinase inhibitors to treat chronic inflammatory and neurological disorders, and the implications this may have on the outcome of pathogen infections. url: https://www.ncbi.nlm.nih.gov/pubmed/32859501/ doi: 10.1016/j.semcdb.2020.08.005 id: cord-256838-8rzibpbl author: Eng, Yi Shin title: Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples date: 2019-09-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Herbal medicine, including traditional Chinese medicine (TCM), is widely used worldwide. Herbs and TCM formulas contain numerous active molecules. Basically, they are a kind of cocktail therapy. Herb-drug, herb-food, herb-herb, herb-microbiome, and herb-disease interactions are complex. There is potential for both benefit and harm, so only after understanding more of their mechanisms and clinical effects can herbal medicine and TCM be helpful to users. Many pharmacologic studies have been performed to unravel the molecular mechanisms; however, basic and clinical studies of good validity are still not enough to translate experimental results into clinical understanding and to provide tough evidence for better use of herbal medicines. There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Understanding study validation, pharmacologic effects, drug interactions, indications and clinical effects, adverse effects and limitations, can all help clinicians in providing adequate suggestions to patients. At present, it would be better to use herbs and TCM formulas according to their traditional indications matching the disease pathophysiology and their molecular mechanisms. To unravel the molecular mechanisms and understand the benefits and harms of herbal medicine and TCM, there is still much work to be done. url: https://doi.org/10.3390/molecules24193505 doi: 10.3390/molecules24193505 id: cord-325989-nf6ouaq3 author: Es-Saad, Salwa title: Regulators of innate immunity as novel targets for panviral therapeutics date: 2012-09-24 words: 3731.0 sentences: 201.0 pages: flesch: 34.0 cache: ./cache/cord-325989-nf6ouaq3.txt txt: ./txt/cord-325989-nf6ouaq3.txt summary: The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. Better characterization of pathogen-induced immune disorders and newly discovered regulators of innate immunity have now the potential to specifically withdraw prevailing subversion mechanisms and to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies. In the near future, targeting specific regulators of PRR-mediated innate response to withdraw viral subversion mechanisms, and access to novel surrogate measurable effector markers, hold the promise of new panviral therapeutics that will minimize adverse effects associated with type I IFN therapy. abstract: Interferons (IFNs) have long been used as an immunomodulatory therapy for a large array of acute and chronic viral infections. However, IFN therapies have been plagued by severe side effects. The discovery of pathogen recognition receptors (PRR) rejuvenated the interest for immunomodulatory therapies. The successes obtained with Toll-like receptor (TLR) agonists in activating immune cells and as adjuvant for prophylactic vaccines against different viruses paved the way to targeted immunomodulatory therapy. Better characterization of pathogen-induced immune disorders and newly discovered regulators of innate immunity have now the potential to specifically withdraw prevailing subversion mechanisms and to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies. url: https://www.sciencedirect.com/science/article/pii/S1879625712001356 doi: 10.1016/j.coviro.2012.08.009 id: cord-302340-pw2xqhwa author: Feeley, Eric M. title: IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry date: 2011-10-27 words: 9235.0 sentences: 553.0 pages: flesch: 52.0 cache: ./cache/cord-302340-pw2xqhwa.txt txt: ./txt/cord-302340-pw2xqhwa.txt summary: Therefore, we have hypothesized that IFITM proteins inhibit susceptible virus families (Orthomyxoviridae, Flaviviridae, Rhabdoviridae, Filoviridae, and Coronaviridae) during the envelope-dependent early phase of the infection cycle, which extends from viral binding to cell surface receptors through the creation of the fusion pore between viral and host membranes [14, 19, 20] . B) MDCK cells stably overexpressing IFITM3 (MDCK-IFITM3) or empty vector control cells (MDCK-Vector) were exposed for 2 h to viral pseudoparticles containing a BLAM-Vpr and expressing either the HA and NA envelope proteins of Influenza A virus (WSN/33, H1N1pp) or the VSV-G envelope protein (VSV-Gpp), then loaded with CCF2. Our assays showed that incoming influenza A viruses were retained in the expanded acidic compartments of both the IFITM3 overexpressing cell lines as well as the IFN-c-treated MEFs, and that IFITM3 partially localized to these structures ( Fig. 2-4, S2-4, S6) . abstract: To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats. url: https://www.ncbi.nlm.nih.gov/pubmed/22046135/ doi: 10.1371/journal.ppat.1002337 id: cord-343515-fad1yyqx author: Felgenhauer, Ulrike title: Inhibition of SARS–CoV-2 by type I and type III interferons date: 2020-10-09 words: 2934.0 sentences: 157.0 pages: flesch: 53.0 cache: ./cache/cord-343515-fad1yyqx.txt txt: ./txt/cord-343515-fad1yyqx.txt summary: For SARS-CoV-2 (dark gray bars), statistically significant negative correlation coefficients (CC) were obtained for both cell lines, indicating that viral replication is increasingly inhibited by IFN-a. Observations were similar when the input MOI was reduced to 0.001 (Fig. S1 ), except that titers of SARS-CoV-1 in Calu-3 cells were already very low in the absence of any IFN-a, resulting in a nonsignificant effect of additional IFN. Our data thus indicate that (i) if anything, ruxolitinib is an enhancer rather than an inhibitor of SARS-CoV-2 multiplication, and (ii) the boosting effect is most likely due to inhibition of the antiviral JAK/ STAT signaling pathway, because it is not present in the IFN induction-deficient Vero E6 cells. For the statistical testing of the dose-response effect of IFN (type I and III) against SARS-coronaviruses, the typical regression procedures were not applicable because of several values below the detection limit and some ties in the data. abstract: The recently emerged severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2) is the causative agent of the devastating COVID-19 lung disease pandemic. Here, we tested the inhibitory activities of the antiviral interferons of type I (IFN-α) and type III (IFN-λ) against SARS–CoV-2 and compared them with those against SARS–CoV-1, which emerged in 2003. Using two mammalian epithelial cell lines (human Calu-3 and simian Vero E6), we found that both IFNs dose-dependently inhibit SARS–CoV-2. In contrast, SARS–CoV-1 was restricted only by IFN-α in these cell lines. SARS–CoV-2 generally exhibited a broader IFN sensitivity than SARS–CoV-1. Moreover, ruxolitinib, an inhibitor of IFN-triggered Janus kinase/signal transducer and activator of transcription signaling, boosted SARS–CoV-2 replication in the IFN-competent Calu-3 cells. We conclude that SARS–CoV-2 is sensitive to exogenously added IFNs. This finding suggests that type I and especially the less adverse effect–prone type III IFN are good candidates for the management of COVID-19. url: https://doi.org/10.1074/jbc.ac120.013788 doi: 10.1074/jbc.ac120.013788 id: cord-002068-e071ciil author: Feng, Min title: Innate Immune Responses in ALV-J Infected Chicks and Chickens with Hemangioma In Vivo date: 2016-05-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Since the precise mechanism of the innate immune response induced by ALV-J is unknown, we investigated the antiviral innate immune responses induced by ALV-J in chicks and chickens that had developed tumors. Spleen levels of interleukin-6 (IL-6), IL-10, IL-1β, and interferon-β (IFN-β) were not significantly different between the infected chick groups and the control groups from 1 day post hatch to 7 days post hatch. However, IL-6, IL-1β, and IFN-β protein levels in the three clinical samples with hemangiomas were dramatically increased compared to the healthy samples. In addition, the anti-inflammatory cytokine IL-10 increased sharply in two of three clinical samples. We also found a more than 20-fold up-regulation of ISG12-1 mRNA at 1 day post infection (d.p.i.) and a twofold up-regulation of ZC3HAV1 mRNA at 4 d.p.i. However, there were no statistical differences in ISG12-1 and ZC3HAV1 mRNA expression levels in the tumorigenesis phase. ALV-J infection induced a significant increase of Toll-like receptor 7 (TLR-7) at 1 d.p.i. and dramatically increased the mRNA levels of melanoma differentiation-associated gene 5 (MDA5) in the tumorigenesis phase. Moreover, the protein levels of interferon regulatory factor 1 (IRF-1) and signal transducer and activator of transcription 1 (STAT1) were decreased in chickens with tumors. These results suggest that ALV-J was primarily recognized by chicken TLR7 and MDA5 at early and late in vivo infection stages, respectively. ALV-J strain SCAU-HN06 did not induce any significant antiviral innate immune response in 1 week old chicks. However, interferon-stimulated genes were not induced normally during the late phase of ALV-J infection due to a reduction of IRF1 and STAT1 expression. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879323/ doi: 10.3389/fmicb.2016.00786 id: cord-314019-8n0jafsk author: Feng, Qian title: Induction and suppression of innate antiviral responses by picornaviruses date: 2014-07-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The family Picornaviridae comprises of small, non-enveloped, positive-strand RNA viruses and contains many human and animal pathogens including enteroviruses (e.g. poliovirus, coxsackievirus, enterovirus 71 and rhinovirus), cardioviruses (e.g. encephalomyocarditis virus), hepatitis A virus and foot-and-mouth disease virus. Picornavirus infections activate a cytosolic RNA sensor, MDA5, which in turn, induces a type I interferon response, a crucial component of antiviral immunity. Moreover, picornaviruses activate the formation of stress granules (SGs), large aggregates of preassembled mRNPs (messenger ribonucleoprotein particles) to temporarily store these molecules upon cellular stress. Meanwhile, picornaviruses actively suppress these antiviral responses to ensure efficient replication. In this review we provide an overview of the induction and suppression of the MDA5-mediated IFN-α/β response and the cellular stress pathway by picornaviruses. url: https://www.sciencedirect.com/science/article/pii/S1359610114000653 doi: 10.1016/j.cytogfr.2014.07.003 id: cord-000660-tsvzg0ax author: Fensterl, Volker title: Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis date: 2012-05-17 words: 8283.0 sentences: 446.0 pages: flesch: 55.0 cache: ./cache/cord-000660-tsvzg0ax.txt txt: ./txt/cord-000660-tsvzg0ax.txt summary: Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. In contrast, in acute infection by viruses that cause severe pathogenesis and death within a few days after infection, protection is primarily provided by the intrinsic antiviral actions of IFN-induced proteins encoded by the hundreds of IFN-stimulated genes (ISGs) [10] [11] [12] , several of which often contribute to the overall effect of IFN against a given virus. From the above observations, we conclude that after intranasal infection by VSV, Ifit2 protects mice from neuropathogenesis by suppressing replication or spread of the virus in brain neurons. In the complete absence of type I IFN action in the IFNAR 2/2 mice, intranasally infected VSV replicated vigorously not only in brains, but also in livers and lungs ( Figure 7A-C) . abstract: Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355090/ doi: 10.1371/journal.ppat.1002712 id: cord-289413-mbrw85og author: Flego, Michela title: Intracellular human antibody fragments recognizing the VP35 protein of Zaire Ebola filovirus inhibit the protein activity date: 2019-09-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Ebola hemorrhagic fever is caused by the Ebola filovirus (EBOV), which is one of the most aggressive infectious agents known worldwide. The EBOV pathogenesis starts with uncontrolled viral replication and subversion of both the innate and adaptive host immune response. The multifunctional viral VP35 protein is involved in this process by exerting an antagonistic action against the early antiviral alpha/beta interferon (IFN-α/β) response, and represents a suitable target for the development of strategies to control EBOV infection. Phage display technology permits to select antibodies as single chain Fragment variable (scFv) from an artificial immune system, due to their ability to specifically recognize the antigen of interest. ScFv is ideal for genetic manipulation and to obtain antibody constructs useful for targeting either antigens expressed on cell surface or intracellular antigens if the scFv is expressed as intracellular antibody (intrabody) or delivered into the cells. RESULTS: Monoclonal antibodies (mAb) in scFv format specific for the EBOV VP35 were isolated from the ETH-2 library of human recombinant antibodies by phage display technology. Five different clones were identified by sequencing, produced in E.coli and expressed in CHO mammalian cells to be characterized in vitro. All the selected scFvs were able to react with recombinant VP35 protein in ELISA, one of the scFvs being also able to react in Western Blot assay (WB). In addition, all scFvs were expressed in cell cytoplasm as intrabodies; a luciferase reporter gene inhibition assay performed in A549 cells showed that two of the scFvs can significantly hamper the inhibition of the IFN-β-induced RIG-I signaling cascade mediated by EBOV VP35. CONCLUSION: Five antibodies in scFv format recognize an active form of EBOV VP35 in ELISA, while one antibody also recognizes VP35 in WB. Two of these scFvs were also able to interfere with the intracellular activity of VP35 in a cell system in vitro. These findings suggest that such antibodies in scFv format might be employed to develop therapeutic molecules able to hamper EBOV infections. url: https://doi.org/10.1186/s12896-019-0554-2 doi: 10.1186/s12896-019-0554-2 id: cord-016343-wc3i54fc author: Frese, Michael title: Interferon-Induced Effector Proteins and Hepatitis C Virus Replication date: 2008 words: 10097.0 sentences: 503.0 pages: flesch: 45.0 cache: ./cache/cord-016343-wc3i54fc.txt txt: ./txt/cord-016343-wc3i54fc.txt summary: RdRp, RNA-dependent RNA polymerase; IRES, internal ribosome entry site; 5BSL3.2, stem loop 3.2 within the coding sequence of NS5B normally result in the production of type I IFNs and the subsequent expression of IFN-induced effector proteins, which in turn would establish an antiviral state in the IFN-producing cell itself and in neighboring cells. Since MxA has the ability to efficiently inhibit a variety of different RNA viruses, MxA was the first IFN-induced effector protein to be analyzed for its antiviral activity in the HCV replicon system (Frese et al., 2001) . Rather indirect evidence that the OAS/RNase L pathway may indeed target HCV replication/translation was recently provided by Taguchi and co-workers, who reported that the N-terminal portion of NS5A (amino acids 1 to 148), which lacks the so-called PKR-binding domain, binds to OAS proteins and there by counteract the antiviral activity of IFN-α (Taguchi et al., 2004) . abstract: Hepatitis C virus (HCV) is a small, enveloped RNA virus that is often capable of establishing a persistent infection, which may lead to chronic liver disease, cirrhosis, hepatocellular carcinoma, and eventually death. For more than 20 years, hepatitis C patients have been treated with interferon-alpha (IFN-α). Current treatment usually consists of polyethylene glycol-conjugated IFN-α that is combined with ribavirin, but even the most advanced IFN-based therapies are still ineffective in eliminating the virus from a large proportion of individuals. Therefore, a better understanding of the IFN-induced innate immune response is urgently needed. By using selectable self-replicating RNAs (replicons) and, more recently, recombinant full-length genomes, many groups have tried to elucidate the mechanism(s) by which IFNs inhibit HCV replication. This chapter attempts to summarize the current state of knowledge in this interesting field of HCV research. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120596/ doi: 10.1007/978-0-387-71376-2_6 id: cord-003261-fz8ucwwm author: Freundt, Eric C. title: Innate Immune Detection of Cardioviruses and Viral Disruption of Interferon Signaling date: 2018-10-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Cardioviruses are members of the Picornaviridae family and infect a variety of mammals, from mice to humans. Replication of cardioviruses produces double stranded RNA that is detected by helicases in the RIG-I-like receptor family and leads to a signaling cascade to produce type I interferon. Like other viruses within Picornaviridae, however, cardioviruses have evolved several mechanisms to inhibit interferon production. In this review, we summarize recent findings that have uncovered several proteins enabling efficient detection of cardiovirus dsRNA and discuss which cell types may be most important for interferon production in vivo. Additionally, we describe how cardiovirus proteins L, 3C and L(∗) disrupt interferon production and antagonize the antiviral activity of interferon effector molecules. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194174/ doi: 10.3389/fmicb.2018.02448 id: cord-289101-ko1knslk author: Fu, Weihui title: An open-label, randomized trial of the combination of IFN-κ plus TFF2 with standard care in the treatment of patients with moderate COVID-19 date: 2020-09-20 words: 6194.0 sentences: 315.0 pages: flesch: 48.0 cache: ./cache/cord-289101-ko1knslk.txt txt: ./txt/cord-289101-ko1knslk.txt summary: Our previous clinical pilot study indicated that aerosol inhalation of IFN-k plus TFF2 is a safe treatment and is able to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby resulting in an early release from hospitalization without induction of a proinflammatory response [20] . This study demonstrated that the combination inhalation of IFN-k and TFF2 is able to shorten the time of viral RNA negative conversion and CT improvement, and facilitating patients early discharge from the hospital, in the absence of induction of a proinflammatory response and treatment-related adverse events. The primary endpoint was a significantly shorter time (Mean 3¢80 days, 95% CI 2¢07À5¢53) from the start of the study treatment to viral RNA negative conversion for SARS-CoV-2 in all clinical samples, including nasopharyngeal swabs, throat swabs and stool swabs, in experimental group than in control group (7¢40 days, 95% CI 4¢57À10¢23) (p = 0¢031), and difference between means was 3¢60 days (Fig. 2A) . abstract: BACKGROUND: Epidemic outbreaks caused by SARS-CoV-2 are worsening around the world, and there are no target drugs to treat COVID-19. IFN-κ inhibits the replication of SARS-CoV-2; and TFF2 is a small secreted polypeptide that promotes the repair of mucosal injury and reduces the inflammatory responses. We used the synergistic effect of both proteins to treat COVID-19. METHODS: We conducted an open-label, randomized, clinical trial involving patients with moderate COVID-19. Patients were assigned in a 1:1 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2 every 24 h for six consecutive dosages in addition to standard care (experimental group) or standard care alone (control group). The primary endpoint was the time until a viral RNA negative conversion for SARS-CoV-2 in all clinical samples. The secondary clinical endpoint was the time of CT imaging improvement. Data analysis was performed per protocol. This study was registered with chictr.org.cn, ChiCTR2000030262. FINDINGS: Between March 23 and May 23 of 2020, 86 COVID-19 patients with symptoms of moderate illness were recruited, and 6 patients were excluded due to not matching the inclusion criteria (patients with pneumonia through chest radiography). Among the remaining 80 patients, 40 patients were assigned to experimental group, and the others were assigned to control group to only receive standard care. Efficacy and safety were evaluated for both groups. The time of viral RNA negative conversion in experimental group (Mean, 3·80 days, 95% CI 2·07–5·53), was significantly shorter than that in control group (7·40 days, 95% CI 4·57 to 10·23) (p = 0.031), and difference between means was 3·60 days. The percentage of patients in experimental group with reversion to negative viral RNA was significantly increased compared with control group on all sampling days (every day during the 12-day observation period) (p = 0·037). For the secondary endpoint, the experimental group had a significantly shorter time until improvement was seen by CT (Mean 6·21 days, N = 38/40, 95% CI 5·11–7·31) than that in control group (8·76 days, N = 34/40, 95% CI 7·57–9·96) (p = 0.002), and difference between means was 2·55 days. No discomfort or complications during aerosol inhalation were reported to the nurses by any experimental patients. INTERPRETATION: In conclusion, we found that aerosol inhalation of IFN-κ plus TFF2 in combination with standard care is safe and superior to standard care alone in shortening the time up to viral RNA negative conversion in all clinical samples. In addition, the patients in experimental group had a significantly shortened CT imaging improvement time than those in control group. This study suggested that this combination treatment is able to facilitate clinical improvement (negative for virus, improvement by CT, reduced hospitalization stay) and thereby result in an early release from the hospital. These data support the need for exploration with a large-scale trial of IFN-κ plus TFF2 to treat COVID-19. FUNDING: Funding was provided by the National Natural Science Foundation of China, National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission. url: https://doi.org/10.1016/j.eclinm.2020.100547 doi: 10.1016/j.eclinm.2020.100547 id: cord-347225-gh51ag2x author: Fu, Weihui title: A clinical pilot study on the safety and efficacy of aerosol inhalation treatment of IFN-κ plus TFF2 in patients with moderate COVID-19 date: 2020-07-29 words: 4921.0 sentences: 233.0 pages: flesch: 46.0 cache: ./cache/cord-347225-gh51ag2x.txt txt: ./txt/cord-347225-gh51ag2x.txt summary: INTERPRETATION: Aerosol inhalation of IFN-κ plus TFF2 is a safe treatment and is likely to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby achieves an early release from hospitalization. Therefore, to evaluate the efficacy and safety of intranasal inhalation of TFF2 and IFN-k protein for SARS-CoV-2 infection, we conducted an open-label, nonrandomized, clinical trial in adult patients hospitalized with moderate COVID-19 disease in China. In this trial, any AE from the beginning of aerosol inhalation to 5 days after the end of the last aerosol inhalation were taken as an adverse event during treatment (TEAE); The secondary objective of the pilot study was to evaluate the clinical efficacy of IFN-k plus TFF2 as compared to the control group as assessed by days of hospitalization staying, CT imaging improvement and cough relief time and negative reversion of viral RNA after 10 days of treatment. abstract: BACKGROUND: The outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health. New and effective intervention strategies are urgently needed to combat the disease. METHODS: We conducted an open-label, non-randomized, clinical trial involving moderate COVID-19 patients according to study protocol. Patients were assigned in a 1:2 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2, every 48 h for three consecutive dosages, in addition to standard treatment (experimental group), or standard treatment alone (control group). The end point was the time to discharge from the hospital. This study is registered with chictr.org.cn, ChiCTR2000030262. FINDINGS: A total of thirty-three eligible COVID-19 patients were enrolled from February 1, 2020 to April 6, 2020, eleven were assigned to the IFN-κ plus TFF2 group, and twenty-two to the control group. Safety and efficacy were evaluated for both groups. No treatment-associated severe adverse effects (SAE) were observed in the group treated with aerosol inhalation of IFN-κ plus TFF2, and no significant differences in the safety evaluations were observed between experimental and control groups. CT imaging was performed in all patients with the median improvement time of 5(.)0 days (IQR 3(.)0–9(.)0) in the experimental group versus 8(.)5 days (IQR 3(.)0–17(.)0) in the control group (p<0(.)05). In addition, the experimental group had a significant shorten median time in cough relief (4(.)5 days [IQR 2(.)0–7(.)0]) than the control group did (10(.)0 days [IQR 6(.)0–21(.)0])(p<0(.)005), in viral RNA reversion of 6(.)0 days (IQR 2(.)0–13(.)0) in the experimental group vs 9.5 days (IQR 3(.)0–23(.)0) in the control group (p < 0(.)05), and in the median hospitalization stays of 12(.)0 days (IQR 7.0–20.0) in the experimental group vs 15(.)0 days (IQR 10.0–25.0) in the control group (p<0(.)001), respectively. INTERPRETATION: Aerosol inhalation of IFN-κ plus TFF2 is a safe treatment and is likely to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby achieves an early release from hospitalization. These data support to explore a scale-up trial with IFN-κ plus TFF2. FUNDING: National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission. url: https://doi.org/10.1016/j.eclinm.2020.100478 doi: 10.1016/j.eclinm.2020.100478 id: cord-257077-cdnkk6ou author: Gabor, Kristin A. title: Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish date: 2013-07-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Understanding spatial distribution and dynamics of receptors within unperturbed membranes is essential for elucidating their role in antiviral signaling, but conventional studies of detergent-resistant membrane fractions cannot provide this information. Caveolae are integral to numerous signaling pathways and these membrane domains have been previously implicated in viral entry but not antiviral defense. This study shows, for the first time, the importance of spatio-temporal regulation of signaling receptors and the importance of the regulation of clustering for downstream signaling. A novel mechanism for virus evasion of host cell defenses is demonstrated through disruption of clusters of signaling molecules organized within caveolin-rich domains. Viral infection leads to a downregulation in Caveolin-1b (Cav-1b), disrupting clusters of CRFB1, a zebrafish type I interferon receptor (–R) subunit. Super-resolution microscopy has enabled the first single-molecule imaging of CRFB1 association with cav-1b-containing membrane domains. Strikingly, downregulation of Cav-1b, the major protein component of caveolae, caused CRFB1 clusters to disperse. Dispersal of CRFB1 clusters led to a suppressed antiviral immune response both in vitro and in vivo, through abrogation of downstream signaling. This response strongly suggests that CRFB1 organization within cav-1b-containing membrane domains is critical for IFN-mediated antiviral defense and presents a previously undescribed antiviral evasion strategy to alter IFN signaling and the antiviral immune response. url: https://www.ncbi.nlm.nih.gov/pubmed/23874753/ doi: 10.1371/journal.pone.0068759 id: cord-338602-6n309bnp author: Gadotti, Ana Carolina title: IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection date: 2020-09-23 words: 2888.0 sentences: 183.0 pages: flesch: 53.0 cache: ./cache/cord-338602-6n309bnp.txt txt: ./txt/cord-338602-6n309bnp.txt summary: title: IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors. A reasonable hypothesis is that (i) pro-inflammatory innate immunity and (ii) anti-inflammatory system are related to disease severity or death once IL-6, IL-8, and IL10 are closely described as prognostic factors in patients diagnosed with COVID-19 1, 3, 7 . Previous studies have not reported the association between IFN-γ and death, even evaluating the COVID-19-reactive CD69+ expressing IFN-γ producing CD8+ T in 25 patients with severe and moderate disease 22 . Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan Levels of cytokines from patients with moderate and severe COVID-19 infection according to the outcome (data in the median with IQR) abstract: BACKGROUND: Innate and adaptive immune responses have been evaluated in infected patients with COVID-19. The severity of the disease has been supposed to be associated with some profile not reported with other bacterial and viral pneumonia. We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors. METHODS: A prospective cohort with moderate and severe cases of COVID-19 infection from June to July 2020. Blood samples from patients were collected regularly to evaluate IFN-γ, TNF-α, IL-4, IL-6, and IL-10. Clinical, laboratory, radiological data, and outcomes were recorded. The outcome variable was in-hospital death, survival, mechanical ventilation, and admission at the intensive care unit. Data are presented in median and interquartile range [IQR]. RESULTS: We evaluated the Th1 and Th2 responses according to evolution, distinguishing possible predictive markers. The IFN-γ median of 323 pg/mL [IQR 166-570] was found in patients who died and 208 pg/mL [IQR 155-392] in the survival group (p = 0.017). IFN-γ was also higher in the early stages of the disease (394 pg/mL [IQR 229-575] against 162 pg/mL [IQR 117-259], p < 0.001). IL-4 that was increased in late-stage (182 pg/mL [IQR 162-199] against 131 pg/mL [IQR 124-152], p < 0.001) but not associated with mortality. Also, death was also related to male gender (relative risk = 1.5 [95% confidence interval = 1.1-2.0]). CONCLUSION: Our results suggest that the activation of the host immune response between Th1 or Th2 in COVID-19 infection may be related to the final result between discharge or death. This implies an attempt to control cytokines, such as IFN-γ, with combined therapies for clinical treatment. url: https://www.sciencedirect.com/science/article/pii/S0168170220310789?v=s5 doi: 10.1016/j.virusres.2020.198171 id: cord-280960-88hzovg2 author: Galani, I. E. title: Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison date: 2020-08-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A central paradigm of immunity is that interferon (IFN) mediated antiviral responses precede the pro-inflammatory ones, optimizing host protection and minimizing collateral damage. Here, we report that for COVID-19 this does not apply. By investigating temporal IFN and inflammatory cytokine patterns in 32 COVID-19 patients hospitalized for pneumonia and longitudinally followed for the development of respiratory failure and death, we reveal that IFN-{lambda} and type I IFN production is both diminished and delayed, induced only in a fraction of patients as they become critically ill. On the contrary, pro-inflammatory cytokines such as TNF, IL-6 and IL-8 are produced before IFNs, in all patients, and persist for a prolonged time. By comparison, in 16 flu patients hospitalized for pneumonia with similar clinicopathological characteristics to COVID-19 and 24 milder non-hospitalized flu patients IFN-{lambda} and type I IFN are robustly induced, earlier, at higher levels and independently of disease severity, while pro-inflammatory cytokines are only acutely and transiently produced. Notably, higher IFN-{lambda} levels in COVID-19 patients correlate with lower viral load in bronchial aspirates and faster viral clearance, and a higher IFN-{lambda}:type I IFN ratio with improved outcome of critically ill patients. Moreover, altered cytokine patterns in COVID-19 patients correlate with longer hospitalization time and higher incidence of critical disease and mortality compared to flu. These data point to an untuned antiviral response in COVID-19 contributing to persistent viral presence, hyperinflammation and respiratory failure. url: http://medrxiv.org/cgi/content/short/2020.08.21.20179291v1?rss=1 doi: 10.1101/2020.08.21.20179291 id: cord-000554-p4ufea6x author: Gao, Wei title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus date: 2012-01-18 words: 5516.0 sentences: 289.0 pages: flesch: 54.0 cache: ./cache/cord-000554-p4ufea6x.txt txt: ./txt/cord-000554-p4ufea6x.txt summary: title: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus We have also observed cross-talk between MAP kinase and NFkB pathways, and our data indicate that MAP kinase ERK1/2 and JNK1/2 may impact the activation of NFkB through the induction of RIG-1, leading to IFN-b induction in H1N1pdm-infected swine macrophages. To understand the mechanism of proinflammatory cytokine and TNF family ligand induction in H1N1pdm-infected swine macrophages, we investigated how MAP kinases were activated and whether their signaling pathways were involved in the regulation of various cytokines and TNF family ligands in pig immune cells. To evaluate the role of MAP kinases in the regulation of proinflammatory cytokine responses in H1N1pdm-infected swine macrophages, we pre-treated 3D/4 cells with specific inhibitors for ERK1/2, p38, and JNK1/2 1 hr prior to infection. abstract: Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered “mixing vessels” that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans. Pathogenesis in SIV or H1N1pdm-infected pigs remains poorly characterized. Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs. In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm. The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined. We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were significantly induced and their induction was ERK1/2-dependent. IFN-β and IFN-inducible antiviral Mx and 2′5′-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited. Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-α, critical for apoptosis in pig macrophages. We found that NFκB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFκB responses in pig macrophages. Our data suggest that MAP kinase may activate NFκB through the induction of RIG-1, which leads to the induction of IFN-β in swine macrophages. Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261190/ doi: 10.1371/journal.pone.0030328 id: cord-005119-vsvc437g author: Georgiades, Jerzy A. title: Oral application of cytokines date: 1996 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A number of different laboratories reported on studies with orally administered interferons and cytokines. Their observations extend previous observations which showed that orally administered interferons and cytokines can exert both local and systemic effects. As difficult as it may be to understand how orally administered interferons and cytokines may exert both effects, the increasing number of laboratories that demonstrate biological effects with orally administered cytokines suggests that serious consideration be given to the possibility that orally administered interferons and cytokines can indeed exert effects. They also raise the possibility that these effects may have biological relevance for the treatment of human disease. Moreover, they may indicate that the nasal/oral region is a window on the environment. It is most important, however, to assure that these experiments are performed with special care to avoid presenting preliminary data that is not properly controlled. It is essential to carry out these studies with sufficient animals or patients to ascertain their significance; and to plan the studies as double-blind evaluations to avoid misinterpretations when subjective tests are used. Nevertheless, the overall data presented give one the impression of an area that should be pursued. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088415/ doi: 10.1007/bf01877206 id: cord-315072-b28yikvj author: Giotis, Efstathios S. title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) date: 2016-08-05 words: 5878.0 sentences: 285.0 pages: flesch: 48.0 cache: ./cache/cord-315072-b28yikvj.txt txt: ./txt/cord-315072-b28yikvj.txt summary: title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α) To generate a chicken ISG database we have compared data from three transcriptomic technology platforms: (i) the classical 3′-biased GeneChip Chicken Genome Array (32K; Affymetrix, High Wycombe, UK), (ii) the Chicken Gene 1.0 Sense Target (ST) whole transcriptome Array (Affymetrix) and (iii) Illumina (Little Chesterford, UK) RNA-seq. One of the most highly-expressed contigs was one which, when analysed by BLAST, proved to represent a homologue of STAT2, which is missing from the current ENSEMBL annotated reference chicken genome In (B) PYURF shows 24-fold suppression by IFN but the sequence surrounding PYURF shows 87-fold induction from the right-hand end of the unannotated, antisense LOC422513 and considerably higher upregulation from the left-hand end (due to its lower uninduced levels), consistent with these representing homologues of IFN-inducible human genes HERC6 and HERC5. Technologies identifying significant IRGs are listed as "1" RNA-seq (using Kal''s Z test); "2" Affymetrix 32K GeneChip Chicken Genome Array and "3" Chicken Gene 1.0 ST Array'' . abstract: Viruses that infect birds pose major threats—to the global supply of chicken, the major, universally-acceptable meat, and as zoonotic agents (e.g. avian influenza viruses H5N1 and H7N9). Controlling these viruses in birds as well as understanding their emergence into, and transmission amongst, humans will require considerable ingenuity and understanding of how different species defend themselves. The type I interferon-coordinated response constitutes the major antiviral innate defence. Although interferon was discovered in chicken cells, details of the response, particularly the identity of hundreds of stimulated genes, are far better described in mammals. Viruses induce interferon-stimulated genes but they also regulate the expression of many hundreds of cellular metabolic and structural genes to facilitate their replication. This study focusses on the potentially anti-viral genes by identifying those induced just by interferon in primary chick embryo fibroblasts. Three transcriptomic technologies were exploited: RNA-seq, a classical 3′-biased chicken microarray and a high density, “sense target”, whole transcriptome chicken microarray, with each recognising 120–150 regulated genes (curated for duplication and incorrect assignment of some microarray probesets). Overall, the results are considered robust because 128 of the compiled, curated list of 193 regulated genes were detected by two, or more, of the technologies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0363-8) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/27494935/ doi: 10.1186/s13567-016-0363-8 id: cord-349647-cfjrwt44 author: Girkin, Jason title: Chapter 8 In vivo experimental models of infection and disease date: 2019-12-31 words: 12472.0 sentences: 659.0 pages: flesch: 35.0 cache: ./cache/cord-349647-cfjrwt44.txt txt: ./txt/cord-349647-cfjrwt44.txt summary: However, the recognition that RV infection is associated with more severe clinical manifestations in people with chronic lung diseases such as asthma and COPD provided a new impetus to research and a new direction to human experimental infection studies. 166 These studies extend the use of RV infection in mice to new areas, including mechanisms of early life infection susceptibility, to mechanisms of secondary bacterial infection/compromised antimicrobial immunity and experimental exploration of clinical risk factors associated with increased likelihood to develop virus-induced exacerbations of respiratory diseases. 190 In the same elastase-induced model, fluticasone proprionate treatment reduced IFN responses, increased viral load, suppressed airway immune cell numbers (lymphocytes and neutrophils), suppressed inflammatory cytokines (IL-6, TNFα), and increased mucus production, following RV-A1 exacerbation. Human experimental RV challenge studies have shed light on the biology of RV infection and the mechanisms associated with RV-induced exacerbations of chronic respiratory diseases. abstract: Abstract Human and animal models continue to play a crucial role in research to understand host immunity to rhinovirus (RV) and identify disease mechanisms. Human models have provided direct evidence that RV infection is capable of exacerbating chronic respiratory diseases and identified immunological processes that correlate with clinical disease outcomes. Mice are the most commonly used nonhuman experimental RV infection model. Although semipermissive, under defined experimental conditions sufficient replication occurs to induce host immune responses that recapitulate immunity and disease during human infection. The capacity to use genetically modified mouse strains and drug interventions has shown the mouse model to be an invaluable research tool defining causal relationships between host immunity and disease and supporting development of new treatments. Used in combination the insights achieved from human and animal experimental infection models provide complementary insights into RV biology and yield novel therapeutic options to reduce the burden of RV-induced disease. url: https://www.sciencedirect.com/science/article/pii/B9780128164174000081 doi: 10.1016/b978-0-12-816417-4.00008-1 id: cord-298938-xemarhlv author: Goswami, Biswendu B. title: Apoptosis induced by a cytopathic hepatitis A virus is dependent on caspase activation following ribosomal RNA degradation but occurs in the absence of 2′–5′ oligoadenylate synthetase date: 2004-04-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We have presented previously evidence that the cytopathogenic 18f strain of hepatitis A virus (HAV) induced degradation of ribosomal RNA (rRNA) in infected cells [Arch. Virol. 148 (2003) 1275–1300]. In contrast, the non-cytopathogenic parent virus HM175 clone 1 had no effect on rRNA integrity. We present here data showing that rRNA degradation is followed by apoptosis accompanied by characteristic DNA laddering in the cytoplasm of 18f infected cells. The DNA laddering coincided with the detection of caspase 3 and PARP-1 cleavage and was dependent upon activation of the caspase pathway, since treatment with Z-VAD-FMK, a pan-caspase inhibitor, inhibited both events. RNase L mRNA was present in both virus-infected and uninfected cells. Messenger RNA for the interferon inducible enzyme 2′–5′ oligoadenylate synthetase (2′–5′ OAS), which polymerizes ATP into 2′–5′ oligo adenylate (2–5A, the activator of RNase L) in the presence of double-stranded RNA, was not detected following virus infection. 2′–5′ OAS mRNA was induced by treatment of the cells with interferon-β (IFN-β). IFN-β mRNA was marginally induced following infection. However, phosphorylated STAT 1, a key regulator of interferon-stimulated gene transcription was not detected in virus infected cells. STAT 1 phosphorylation in response to IFN treatment was lower in virus-infected cells, compared to uninfected cells treated with interferon, suggesting that 18f virus infection interferes with interferon signaling. The results suggest that 18f infection causes the induction of a 2–5A independent RNase L like activity. url: https://www.ncbi.nlm.nih.gov/pubmed/15451183/ doi: 10.1016/j.antiviral.2004.02.004 id: cord-000478-88wo4xen author: Gowen, Brian B. title: Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection date: 2011-10-24 words: 4407.0 sentences: 221.0 pages: flesch: 49.0 cache: ./cache/cord-000478-88wo4xen.txt txt: ./txt/cord-000478-88wo4xen.txt summary: Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. Interestingly, the 10 7 and 10 8 pfu DEF201 groups presented with little to no day-7 virus burden in the serum, liver, or spleen, while the 10 6 group developed viral titers that were comparable to the rAd EV and placebo controls ( Figure 2B-D) . This may not be the case with hamsters treated with DEF201 24 h prior to challenge since most had no detectable virus titers in spleen, liver, or serum on day 7 of PICV infection ( Figure 2B-D) . Animals were treated i.n. with a single dose 10 8 pfu of DEF201, the rAd EV control virus, or PBS placebo 7 or 14 days prior to PICV infection. abstract: Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-α) is a licensed protein with broad clinical appeal. However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200317/ doi: 10.1371/journal.pone.0026072 id: cord-277487-jgbjxgh1 author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-06-20 words: 5057.0 sentences: 242.0 pages: flesch: 53.0 cache: ./cache/cord-277487-jgbjxgh1.txt txt: ./txt/cord-277487-jgbjxgh1.txt summary: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. Analysis of SARS-CoV-2 S protein-specific murine splenocyte responses by IFNγ ELISpot assay showed no statistically significant difference between the prime-only and primeboost vaccination regimens, in either strain of mouse ( Figure 1A ). IFN-γ ELISpot analysis of porcine peripheral blood mononuclear cells (PBMC) showed responses on 42 dpv (2 weeks after boost) that were significantly greater in the prime-boost pigs compared to prime-only animals (p < 0.05; Figure 1C ). : SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 primeonly and prime-boost vaccination regimens in mice and pigs. abstract: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. url: https://doi.org/10.1101/2020.06.20.159715 doi: 10.1101/2020.06.20.159715 id: cord-353826-owoec2ud author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-07-27 words: 5496.0 sentences: 269.0 pages: flesch: 53.0 cache: ./cache/cord-353826-owoec2ud.txt txt: ./txt/cord-353826-owoec2ud.txt summary: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Analysis of SARS-CoV-2 S proteinspecific murine splenocyte responses by IFN-γ ELISpot assay showed no statistically significant difference between the primeonly and prime-boost vaccination regimens, in either strain of mouse (Fig. 1a) . SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 prime-only and prime-boost vaccination regimens in mice and pigs SARS-CoV-2 S protein-specific antibody titres in serum were determined by ELISA using recombinant soluble trimeric S (FL-S) and receptor binding domain (RBD) proteins. Small animal models have variable success in predicting vaccine efficacy in larger animals but are an important To analyse SARS-CoV-2 S-specific T cell responses, all mice were sacrificed on day 49 for isolation of splenocytes and pigs were blood sampled longitudinally to isolate PBMC. abstract: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. url: https://doi.org/10.1038/s41541-020-00221-3 doi: 10.1038/s41541-020-00221-3 id: cord-325825-0lyt8gfq author: Griffiths, Samantha J. title: A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date: 2013-08-08 words: 12504.0 sentences: 601.0 pages: flesch: 45.0 cache: ./cache/cord-325825-0lyt8gfq.txt txt: ./txt/cord-325825-0lyt8gfq.txt summary: Host factors (HFs) which positively or negatively regulate HSV-1 replication were identified by screening a druggable genome siRNA library (4 siRNAs per gene) targeting 7,237 human genes against a HSV-1 reporter virus expressing the enhanced green fluorescent protein (eGFP; HSV-1 strain C12) in the epithelial Hela cell line, due to their ease of transfection and susceptibility to HSV-1 infection [34] . Combined bioinformatic analyses of protein interaction and siRNA depletion screens found a significant functional enrichment for proteins involved in transcription, and identified multi-protein complexes enriched for pro-viral HFs which strongly inhibited HSV-1 upon depletion, including the RNA-polymerase II, eIF3 and Mediator complexes ( Figure 3a) . Furthermore, qPCR analysis found depletion of Med23 inhibited the induction of IFN-l expression following HSV-1 infection of A549 cells in comparison to cells transfected with the RSCF siRNA control ( Figure 4e ). abstract: Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome. url: https://doi.org/10.1371/journal.ppat.1003514 doi: 10.1371/journal.ppat.1003514 id: cord-329424-hmsidrc7 author: Grunwell, Jocelyn R. title: Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome date: 2020-11-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Acute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recruitment of large numbers of neutrophils into the lungs. Neutrophils isolated from the blood of adults with ARDS have elevated expression of interferon (IFN) stimulated genes (ISGs) associated with decreased capacity of neutrophils to kill Staphylococcus aureus and worse clinical outcomes. Neutrophil extracellular traps (NETs) are elevated in adults with ARDS. Whether pediatric ARDS (PARDS) is similarly associated with altered neutrophil expression of ISGs and neutrophil extracellular trap release is not known. Tracheal aspirate fluid and cells were collected within 72 h from seventy-seven intubated children. Primary airway neutrophils were analyzed for differential ISG expression by PCR, STAT1 phosphorylation and markers of degranulation and activation by flow cytometry. Airway fluid was analyzed for the release of NETs by myeloperoxidase-DNA complexes using an ELISA. Higher STAT1 phosphorylation, markers of neutrophil degranulation, activation and NET release were found in children with versus without PARDS. Higher NETs were detected in the airways of children with ventilator-free days less than 20 days. Increased airway cell IFN signaling, neutrophil activation, and NET production is associated with PARDS. Higher levels of airway NETs are associated with fewer ventilator-free days. url: https://www.ncbi.nlm.nih.gov/pubmed/33149247/ doi: 10.1038/s41598-020-76122-1 id: cord-013481-3zwq67do author: Guo, Kejun title: Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis date: 2020-10-16 words: 9552.0 sentences: 494.0 pages: flesch: 51.0 cache: ./cache/cord-013481-3zwq67do.txt txt: ./txt/cord-013481-3zwq67do.txt summary: The Type I Interferons (IFN-Is) are innate antiviral cytokines that include 12 different IFNα subtypes and IFNβ that signal through the IFN-I receptor (IFNAR), inducing hundreds of IFN-stimulated genes (ISGs) that comprise the ''interferome''. Since IFNβ, and not IFNα, is upregulated during chronic HIV-1 infection in the gut, we compared core ISGs and IFNβ-specific ISGs from colon pinch biopsies of HIV-1-uninfected (n = 13) versus ageand gender-matched, antiretroviral-therapy naïve persons with HIV-1 (PWH; n = 19). We recently reported that during chronic, untreated HIV-1 infection, IFN-I inducible antiretroviral genes APOBEC3G, BST2 and MX2, as well as IFNβ, but not IFNα, were expressed to significantly higher levels when compared to HIV-1 uninfected individuals [38] . These data suggest that increased IFNβ in the gut of chronic PWH may drive genes associated with sustained ISG expression, antigen processing, T cell activation, inflammation and immune exhaustion. abstract: The Type I Interferons (IFN-Is) are innate antiviral cytokines that include 12 different IFNα subtypes and IFNβ that signal through the IFN-I receptor (IFNAR), inducing hundreds of IFN-stimulated genes (ISGs) that comprise the ‘interferome’. Quantitative differences in IFNAR binding correlate with antiviral activity, but whether IFN-Is exhibit qualitative differences remains controversial. Moreover, the IFN-I response is protective during acute HIV-1 infection, but likely pathogenic during the chronic stages. To gain a deeper understanding of the IFN-I response, we compared the interferomes of IFNα subtypes dominantly-expressed in HIV-1-exposed plasmacytoid dendritic cells (1, 2, 5, 8 and 14) and IFNβ in the earliest cellular targets of HIV-1 infection. Primary gut CD4 T cells from 3 donors were treated for 18 hours ex vivo with individual IFN-Is normalized for IFNAR signaling strength. Of 1,969 IFN-regulated genes, 246 ‘core ISGs’ were induced by all IFN-Is tested. However, many IFN-regulated genes were not shared between the IFNα subtypes despite similar induction of canonical antiviral ISGs such as ISG15, RSAD2 and MX1, formally demonstrating qualitative differences between the IFNα subtypes. Notably, IFNβ induced a broader interferome than the individual IFNα subtypes. Since IFNβ, and not IFNα, is upregulated during chronic HIV-1 infection in the gut, we compared core ISGs and IFNβ-specific ISGs from colon pinch biopsies of HIV-1-uninfected (n = 13) versus age- and gender-matched, antiretroviral-therapy naïve persons with HIV-1 (PWH; n = 19). Core ISGs linked to inflammation, T cell activation and immune exhaustion were elevated in PWH, positively correlated with plasma lipopolysaccharide (LPS) levels and gut IFNβ levels, and negatively correlated with gut CD4 T cell frequencies. In sharp contrast, IFNβ-specific ISGs linked to protein translation and anti-inflammatory responses were significantly downregulated in PWH, negatively correlated with gut IFNβ and LPS, and positively correlated with plasma IL6 and gut CD4 T cell frequencies. Our findings reveal qualitative differences in interferome induction by diverse IFN-Is and suggest potential mechanisms for how IFNβ may drive HIV-1 pathogenesis in the gut. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592919/ doi: 10.1371/journal.ppat.1008986 id: cord-282242-5tkhjiwl author: Gómez-Laguna, J. title: Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus date: 2009-08-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine reproductive and respiratory syndrome (PRRS) is caused by a virus that predominantly replicates in alveolar macrophages. The aim of the present study was to characterize the production of cytokines by subpopulations of pulmonary macrophages in pigs infected by the PRRS virus (PRRSV). Expression of interleukin (IL) 1α, IL-6 and tumour necrosis factor (TNF)-α correlated with the severity of pulmonary pathology and the numbers of pulmonary macrophages. Significant correlations were observed between PRRSV infection and the expression of IL-10, between the expression of IL-12p40 and interferon (IFN)-γ, and between the expression of TNF-α and IFN-γ. These findings suggest that PRRSV modulates the immune response by the up-regulation of IL-10, which may in turn reduce expression of cytokines involved in viral clearance (e.g. IFN-α, IFN-γ, IL-12p40 and TNF-α). The results also suggest that expression of IFN-γ is stimulated by IL-12p40 and TNF-α, but not by IFN-α. All of these cytokines were expressed mainly by septal macrophages with weaker expression by alveolar macrophages, lymphocytes and neutrophils. There appears to be differential activation of septal and alveolar macrophages in PRRSV infection, with septal macrophages being the major source of cytokines. url: https://doi.org/10.1016/j.jcpa.2009.07.004 doi: 10.1016/j.jcpa.2009.07.004 id: cord-329366-xuszdrsa author: Hackbart, Matthew title: Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors date: 2020-04-07 words: 7187.0 sentences: 445.0 pages: flesch: 57.0 cache: ./cache/cord-329366-xuszdrsa.txt txt: ./txt/cord-329366-xuszdrsa.txt summary: In this study, we show that CoV EndoU activity limits the abundance and length of the polyuridine (polyU) extension on 5′-polyU-containing, negative-sense (PUN) RNAs for both the beta-CoV mouse hepatitis virus strain A59 (MHV-A59) and the alpha-CoV PEDV. Overall, we propose a mechanism for EndoU, which is to cleave polyU sequences from PUN RNAs, thus limiting the formation of a PAMP and impeding the ability of MDA5 to activate the innate immune response to infection. EndoU Activity Limits Abundance and Length of PUN RNAs. Previous studies showed that the 5′ end of the CoV negative-sense RNA contains polyU extensions (35) , and that EndoU cleaves at uridine residues (22, 25, (27) (28) (29) (30) . We found that the products generated from positive-sense RNA were similar between wild-type and EndoUmut viruses, consistent with our previous results indicating that the polyA tail is not cleaved by EndoU activity (Fig. 5C ). abstract: Coronaviruses (CoVs) are positive-sense RNA viruses that can emerge from endemic reservoirs and infect zoonotically, causing significant morbidity and mortality. CoVs encode an endoribonuclease designated EndoU that facilitates evasion of host pattern recognition receptor MDA5, but the target of EndoU activity was not known. Here, we report that EndoU cleaves the 5′-polyuridines from negative-sense viral RNA, termed PUN RNA, which is the product of polyA-templated RNA synthesis. Using a virus containing an EndoU catalytic-inactive mutation, we detected a higher abundance of PUN RNA in the cytoplasm compared to wild-type−infected cells. Furthermore, we found that transfecting PUN RNA into cells stimulates a robust, MDA5-dependent interferon response, and that removal of the polyuridine extension on the RNA dampens the response. Overall, the results of this study reveal the PUN RNA to be a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP). We also establish a mechanism for EndoU activity to cleave and limit the accumulation of this PAMP. Since EndoU activity is highly conserved in all CoVs, inhibiting this activity may serve as an approach for therapeutic interventions against existing and emerging CoV infections. url: https://doi.org/10.1073/pnas.1921485117 doi: 10.1073/pnas.1921485117 id: cord-007417-az8xd66p author: Hansbro, Nicole G. title: Understanding the mechanisms of viral induced asthma: New therapeutic directions date: 2008-01-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Asthma is a common and debilitating disease that has substantially increased in prevalence in Western Societies in the last 2 decades. Respiratory tract infections by respiratory syncytial virus (RSV) and rhinovirus (RV) are widely implicated as common causes of the induction and exacerbation of asthma. These infections in early life are associated with the induction of wheeze that may progress to the development of asthma. Infections may also promote airway inflammation and enhance T helper type 2 lymphocyte (Th2 cell) responses that result in exacerbations of established asthma. The mechanisms of how RSV and RV induce and exacerbate asthma are currently being elucidated by clinical studies, in vitro work with human cells and animal models of disease. This research has led to many potential therapeutic strategies and, although none are yet part of clinical practise, they show much promise for the prevention and treatment of viral disease and subsequent asthma. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112677/ doi: 10.1016/j.pharmthera.2007.11.002 id: cord-023392-axd0901z author: Hansen, T. K. title: Association between Mannose‐Binding Lectin and Vascular Complications in Type 1 Diabetes date: 2008-06-28 words: 16944.0 sentences: 875.0 pages: flesch: 46.0 cache: ./cache/cord-023392-axd0901z.txt txt: ./txt/cord-023392-axd0901z.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Complement activation and inflammation have been suggested in the pathogenesis of diabetic vascular lesions. We investigated serum mannose‐binding lectin (MBL) levels and polymorphisms in the MBL gene in type 1 diabetic (T1DM) patients with and without diabetic nephropathy and associated macrovascular complications. Polymorphisms in the MBL gene and serum MBL levels were determined in 199 T1DM patients with overt nephropathy and 192 T1DM patients with persistent normoalbuminuria matched for age, sex and duration of diabetes as well as in 100 healthy control subjects. The frequencies of high and low expression MBL genotypes were similar in patients with T1DM and healthy controls. High MBL genotypes were significantly more frequent in diabetic patients with nephropathy than in the normoalbuminuric group, and the risk of having nephropathy, given a high MBL genotype, assessed by odds ratio was 1.52 (1.02–2.27), P = 0.04. Median serum MBL concentrations were significantly higher in patients with nephropathy than in patients with normoalbuminuria [2306 µg/l (IQR 753–4867 µg/l) versus 1491 µg/l (IQR 577–2944), P = 0.0003], and even when comparing patients with identical genotypes, serum MBL levels were higher in the nephropathy group than in the normoalbuminuric group. Patients with a history of cardiovascular disease had significantly elevated MBL levels independently of nephropathy status [3178 µg/l (IQR 636–5231 µg/l) versus 1741 µg/l (IQR 656–3149 µg/l), P = 0.02]. The differences in MBL levels between patients with and without vascular complications were driven primarily by pronounced differences among carriers of high MBL genotypes (P < 0.0001). Our findings suggest that MBL may be involved in the pathogenesis of microvascular and macrovascular complications in type 1 diabetes and that determination of MBL status might be used to identify patients at increased risk of developing these complications. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169517/ doi: 10.1111/j.0300-9475.2004.01423i.x id: cord-258685-ayek8zbo author: Har-Noy, Michael title: Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak date: 2020-05-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next ‘Disease X’. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim(®)) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim(®) creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an “anti-viral state”, by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter. CONCLUSION: Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism. url: https://doi.org/10.1186/s12967-020-02363-3 doi: 10.1186/s12967-020-02363-3 id: cord-007382-5kb16qb7 author: Hartmann, G. title: Nucleic Acid Immunity date: 2016-12-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to advance medicine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112058/ doi: 10.1016/bs.ai.2016.11.001 id: cord-334624-chnibsa1 author: Hayn, Manuel title: Imperfect innate immune antagonism renders SARS-CoV-2 vulnerable towards IFN-γ and -λ date: 2020-10-30 words: 5355.0 sentences: 432.0 pages: flesch: 57.0 cache: ./cache/cord-334624-chnibsa1.txt txt: ./txt/cord-334624-chnibsa1.txt summary: Here, we systematically assessed the impact of 29 SARS-CoV-2 proteins on viral sensing, type I, II and III interferon (IFN) signaling, autophagy and inflammasome formation. Our results identify ineffective type I and II antagonism as weakness of SARS-CoV-2 that may allow to devise safe and effective anti-viral therapies based on targeted innate immune activation. SARS-CoV-1 ORF6 is about 4-fold less potent in antagonizing type I IFN signaling (Fig. 243 4b) but induces higher levels of autophagy (Fig. 4c) . Examination of the functional conservation showed that SARS-CoV-2 Nsp15 was less 319 efficient in blocking innate immune activation, both type I IFN induction and signaling, than SARS-320 Hepatitis C virus viruses to block anti-viral autophagic turnover 50 and thus may represent a common studies will see more mechanistic data to explain the molecular details of the impact of SARS-CoV-2 343 proteins on innate immune activation. abstract: The innate immune system constitutes a powerful barrier against viral infections. However, it may fail because successful emerging pathogens, like SARS-CoV-2, evolved strategies to counteract it. Here, we systematically assessed the impact of 29 SARS-CoV-2 proteins on viral sensing, type I, II and III interferon (IFN) signaling, autophagy and inflammasome formation. Mechanistic analyses show that autophagy and type I IFN responses are effectively counteracted at different levels. For example, Nsp14 induces loss of the IFN receptor, whereas ORF3a disturbs autophagy at the Golgi/endosome interface. Comparative analyses revealed that antagonism of type I IFN and autophagy is largely conserved, except that SARS-CoV-1 Nsp15 is more potent in counteracting type I IFN than its SARS-CoV-2 ortholog. Altogether, however, SARS-CoV-2 counteracts type I IFN responses and autophagy much more efficiently than type II and III IFN signaling. Consequently, the virus is relatively resistant against exogenous IFN-α/β and autophagy modulation but remains highly vulnerable towards IFN-γ and -λ treatment. In combination, IFN-γ and -λ act synergistically, and drastically reduce SARS-CoV-2 replication at exceedingly low doses. Our results identify ineffective type I and II antagonism as weakness of SARS-CoV-2 that may allow to devise safe and effective anti-viral therapies based on targeted innate immune activation. url: https://doi.org/10.1101/2020.10.15.340612 doi: 10.1101/2020.10.15.340612 id: cord-255013-njpuc475 author: He, Xiaocui title: Establishment of Myotis myotis Cell Lines - Model for Investigation of Host-Pathogen Interaction in a Natural Host for Emerging Viruses date: 2014-10-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bats are found to be the natural reservoirs for many emerging viruses. In most cases, severe clinical signs caused by such virus infections are normally not seen in bats. This indicates differences in the virus-host interactions and underlines the necessity to develop natural host related models to study these phenomena. Due to the strict protection of European bat species, immortalized cell lines are the only alternative to investigate the innate anti-virus immune mechanisms. Here, we report about the establishment and functional characterization of Myotis myotis derived cell lines from different tissues: brain (MmBr), tonsil (MmTo), peritoneal cavity (MmPca), nasal epithelium (MmNep) and nervus olfactorius (MmNol) after immortalization by SV 40 large T antigen. The usefulness of these cell lines to study antiviral responses has been confirmed by analysis of their susceptibility to lyssavirus infection and the mRNA patterns of immune-relevant genes after poly I:C stimulation. Performed experiments indicated varying susceptibility to lyssavirus infection with MmBr being considerably less susceptible than the other cell lines. Further investigation demonstrated a strong activation of interferon mediated antiviral response in MmBr contributing to its resistance. The pattern recognition receptors: RIG-I and MDA5 were highly up-regulated during rabies virus infection in MmBr, suggesting their involvement in promotion of antiviral responses. The presence of CD14 and CD68 in MmBr suggested MmBr cells are microglia-like cells which play a key role in host defense against infections in the central nervous system (CNS). Thus the expression pattern of MmBr combined with the observed limitation of lyssavirus replication underpin a protective mechanism of the CNS controlling the lyssavirus infection. Overall, the established cell lines are important tools to analyze antiviral innate immunity in M. myotis against neurotropic virus infections and present a valuable tool for a broad spectrum of future investigations in cellular biology of M. myotis. url: https://www.ncbi.nlm.nih.gov/pubmed/25295526/ doi: 10.1371/journal.pone.0109795 id: cord-254492-42d77vxf author: Heaton, Steven M. title: Ubiquitin in the activation and attenuation of innate antiviral immunity date: 2016-01-11 words: 7382.0 sentences: 477.0 pages: flesch: 39.0 cache: ./cache/cord-254492-42d77vxf.txt txt: ./txt/cord-254492-42d77vxf.txt summary: Here we review how hostand virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression. Methods for this include substrate molecular mimicry, binding and blocking E3-substrate pairs, expressing virally encoded E3s/DUbs, and hijacking host E3s/DUbs. Additionally, a novel mechanism involving ubiquitin chain packaging into nascent virions for subsequent redeployment Viral infection activates danger signals that are transmitted via the retinoic acid-inducible gene 1-like receptor (RLR), nucleotide-binding oligomerization domain-like receptor (NLR), and Toll-like receptor (TLR) protein signaling cascades. Here we review how host-and virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression. RNF125 forms part of this process, ligating K48-linked polyubiquitin chains to the activated CARD of RIG-I and MDA5, leading to proteasome-mediated degradation of both receptors and diminished IFN-I signaling. MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors abstract: Viral infection activates danger signals that are transmitted via the retinoic acid–inducible gene 1–like receptor (RLR), nucleotide-binding oligomerization domain-like receptor (NLR), and Toll-like receptor (TLR) protein signaling cascades. This places host cells in an antiviral posture by up-regulating antiviral cytokines including type-I interferon (IFN-I). Ubiquitin modifications and cross-talk between proteins within these signaling cascades potentiate IFN-I expression, and inversely, a growing number of viruses are found to weaponize the ubiquitin modification system to suppress IFN-I. Here we review how host- and virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression. url: https://www.ncbi.nlm.nih.gov/pubmed/26712804/ doi: 10.1084/jem.20151531 id: cord-023439-r04y1j22 author: Hedegaard, C. J. title: The Role of Immune Complexes Consisting of Myelin Basic Protein (MBP), Anti‐MBP Antibodies and Complement in Promoting CD4(+) T‐cell Responses to MBP in Health and Multiple Sclerosis date: 2008-06-28 words: 16932.0 sentences: 871.0 pages: flesch: 46.0 cache: ./cache/cord-023439-r04y1j22.txt txt: ./txt/cord-023439-r04y1j22.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. abstract: Multiple sclerosis (MS) is an autoimmune condition characterized by degeneration of nerve fibre myelin sheets. A candidate autoantigen, myelin basic protein (MBP), has especially attracted attention. The presence of anti‐MBP antibodies is a predictor of definite MS, but their role in the pathogenesis remains obscure. T cells have long been known to play a pivotal role in the pathogenesis of MS. Recently, an important role for B cells as autoantigen‐presenting cells has been demonstrated in other autoimmune diseases, including rheumatoid arthritis and diabetes. The uptake of MBP by B cells and the presentation of MBP‐derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease‐associated anti‐MBP antibodies in MS patients, respectively. We have investigated the formation of MBP‐containing IC, the binding of MBP to B cells, the MBP‐elicited induction of Th‐cell and B‐cell proliferation and the cytokine production in peripheral blood mononuclear cells (PBMCs) from healthy donors grown in the presence of intact or C‐inactivated serum from healthy donors or patients with MS. While MBP did not induce measurable proliferation of B cells nor CD4(+) T cells, we observed the production of TNF‐α, IFN‐γ and IL‐10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. By contrast, no production of IL‐2, IL‐4 and IL‐5 was detected. We are currently investigating the capability of MS sera to promote the formation of MBP‐containing IC and thereby enhance the cytokine responses, by virtue of elevated anti‐MBP contents. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169603/ doi: 10.1111/j.0300-9475.2004.01423k.x id: cord-347298-7kqrl3rv author: Hedger, M.P. title: Immunology of the Testis and Male Reproductive Tract date: 2010-07-12 words: 21168.0 sentences: 1000.0 pages: flesch: 46.0 cache: ./cache/cord-347298-7kqrl3rv.txt txt: ./txt/cord-347298-7kqrl3rv.txt summary: Thus, it appears unlikely that a lack of APCs is a contributing factor in testicular immune privilege, although differences in the number and distribution of MHC class II-expressing cells in the interstitial tissue of different species or strains may help to explain differences in susceptibility to autoimmune orchitis (Flickinger et al. Moreover, while inhibition of Leydig cell steroidogenesis during inflammation may involve indirect effects at the level of the pituitary, or the actions of inflammatory mediators produced by the testicular macrophages and Sertoli cells, there is evidence that these cells can also respond directly to TLR ligands (Bhushan et al. Activation of p38/Jnk is implicated in the stimulation of proliferation by immature Sertoli cells and the regulation of blood-testis barrier dynamics, steroidogenesis, and multiple inflammatory responses, including the production of IL6, iNOS, monocyte chemoattractant protein 1, and leukocyte adhesion molecules, in the mature Sertoli cell (De Cesaris et al. abstract: A large body of evidence points to the existence of a close, dynamic relationship between the immune system and the male reproductive tract, which has important implications for our understanding of both systems. The testis and the male reproductive tract provide an environment that protects the otherwise highly immunogenic spermatogenic cells and sperm from immunological attack. At the same time, secretions of the testis, including androgens, influence the development and mature functions of the immune system. Activation of the immune system has negative effects on both androgen and sperm production, so that systemic or local infection and inflammation compromise male fertility. The mechanisms underlying these interactions have begun to receive the attention from reproductive biologists and immunologists that they deserve, but many crucial details remain to be uncovered. A complete picture of male reproductive tract function and its response to toxic agents is contingent upon continued exploration of these interactions and the mechanisms involved. url: https://api.elsevier.com/content/article/pii/B978008046884601112X doi: 10.1016/b978-0-08-046884-6.01112-x id: cord-000725-rafwlw0t author: Hindinger, Claudia title: IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability date: 2012-07-27 words: 5114.0 sentences: 243.0 pages: flesch: 37.0 cache: ./cache/cord-000725-rafwlw0t.txt txt: ./txt/cord-000725-rafwlw0t.txt summary: Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. GFAPcR1D and wt mice were compared at the peak of acute disease to determine if IFN-c signaling altered astrocyte activation or CNS inflammation. Despite elevated demyelination and axonal loss in the absence of IFN-c signaling to astrocytes, spinal cords showed no evidence of differential astrocyte activation by either immunohistochemistry (Fig. 4 ), or differences in GFAP mRNA expression during the peak of acute disease (Fig. 5 ). Although demyelination was increased in the CNS of GFAPcR1D mice, the extent of astrocyte activation associated with spinal cord white matter lesions was similar in both groups ( Fig. 6 ; ,60 GFAP + cells/mm 2 ). abstract: Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS). Cells resident within the central nervous system (CNS) are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood. Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination. Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. Nevertheless, increased demyelination at peak acute disease in the absence of IFN-γ signaling to astrocytes correlated with sustained clinical symptoms. Following peak disease, diminished clinical remission, increased mortality and sustained astrocyte activation within the gray matter demonstrate a critical role of IFN-γ signaling to astrocytes in neuroprotection. Diminished disease remission was associated with escalating demyelination, axonal degeneration and sustained inflammation. The CNS infiltrating leukocyte composition was not altered; however, decreased IL-10 and IL-27 correlated with sustained disease. These data indicate that astrocytes play a critical role in limiting CNS autoimmune disease dependent upon a neuroprotective signaling pathway mediated by engagement of IFN-γ receptors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407093/ doi: 10.1371/journal.pone.0042088 id: cord-023388-btbf6wkg author: Hoffmann, H. J. title: Decrease in Fine T‐cell Subset ratio MT2/MT1 During Steroid Reduction of Asthmatic Patients date: 2008-06-28 words: 16918.0 sentences: 871.0 pages: flesch: 46.0 cache: ./cache/cord-023388-btbf6wkg.txt txt: ./txt/cord-023388-btbf6wkg.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Combining inhaled long‐acting β‐2 agonist (LABA) and inhaled corticosteroid (ICS) seems to offer asthma control at a lower dose of ICS than achieved by ICS alone. Fine mapping of T‐cell surface markers by flow cytometry offers a detailed status of the individual's inflammatory response. The frequency of MT2 (CD4(+)CD45RA(–)CD62L(+)CD11adim) and MT1 (CD4(+)CD45RA(–)CD62L(–)CD11abright) cells in peripheral blood, and their ratio, has been shown to differ predictably in atopics and patients with leprosy, where MT2 correlates with a Th2 phenotype and MT1 with a Th1 phenotype. Stable asthmatics, requiring fluticasone propionate (FP) 750–1000 µg daily or equivalent, were randomized to receive, double‐blinded, either Seretide(®)[salmeterol and fluticasone propionate (SFC, n = 16)] 50 µg/500 µg bd or FP 500 µg bd (n = 17). If asthma was controlled based on lung function and symptoms at clinic visits every 6 weeks, ICS dose was tapered until asthma exacerbated or 0 µg was reached. The frequency and ratio of MT2 and MT1 T cells of the patients was monitored at 6 week intervals. As treatment tapered, the frequency of MT2 cells decreased (P = 0038 from first to final visit), whereas that of MT1 cells increased. The ratio of MT2/MT1 decreased (P = 0049 from first to final visit). In patients receiving LABA + ICS, the fall in MT2/MT1 ratio appeared to be more pronounced than in patients receiving ICS alone. Thus, the MT2 phenotype may be associated with stable asthma, whereas an imminent exacerbation may associate with an increase in the MT1 phenotype. LABA may allow for a greater effect of FP on the MT ratio. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169509/ doi: 10.1111/j.0300-9475.2004.01423ah.x id: cord-303344-4aeu9n5v author: Honke, Nadine title: Multiple functions of USP18 date: 2016-11-03 words: 5890.0 sentences: 382.0 pages: flesch: 45.0 cache: ./cache/cord-303344-4aeu9n5v.txt txt: ./txt/cord-303344-4aeu9n5v.txt summary: Lacking of USP18 leads to an increase signaling of IFN-I, IFN-III, TNF-α and high levels of conjugated ISG15 Interestingly, knockout mice generated on the FVB/N genetic background are more viable and do not exhibit the severe neurological symptoms that occur in mice generated on a C57BL/6 background, which develop brain injury because of necrosis of ependymal cells. 53 In addition to ISG15, USP18 also specifically inhibits K63-linked ubiquitination of NEMO, leading to the negative regulation of NF-κB activation induced by the TAK1-TAB complex. As expected, this upregulation inhibits IFN-I-induced genes in human microvascular endothelial cells; however, whether USP18 plays a role in controlling bacterial infection has not yet been fully clarified. Because DCs express more USP18 than do other types of cells, the lack of a response to the antiviral effect of IFN-I leads to augmented viral replication and a sufficient amount of autoantigen. abstract: Since the discovery of the ubiquitin system and the description of its important role in the degradation of proteins, many studies have shown the importance of ubiquitin-specific peptidases (USPs). One special member of this family is the USP18 protein (formerly UBP43). In the past two decades, several functions of USP18 have been discovered: this protein is not only an isopeptidase but also a potent inhibitor of interferon signaling. Therefore, USP18 functions as 'a' maestro of many biological pathways in various cell types. This review outlines multiple functions of USP18 in the regulation of various immunological processes, including pathogen control, cancer development, and autoimmune diseases. url: https://doi.org/10.1038/cddis.2016.326 doi: 10.1038/cddis.2016.326 id: cord-312438-zr9zx7pv author: Hoo, Regina title: Innate Immune Mechanisms to Protect Against Infection at the Human Decidual-Placental Interface date: 2020-09-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: During pregnancy, the placenta forms the anatomical barrier between the mother and developing fetus. Infectious agents can potentially breach the placental barrier resulting in pathogenic transmission from mother to fetus. Innate immune responses, orchestrated by maternal and fetal cells at the decidual-placental interface, are the first line of defense to avoid vertical transmission. Here, we outline the anatomy of the human placenta and uterine lining, the decidua, and discuss the potential capacity of pathogen pattern recognition and other host defense strategies present in the innate immune cells at the placental-decidual interface. We consider major congenital infections that access the placenta from hematogenous or decidual route. Finally, we highlight the challenges in studying human placental responses to pathogens and vertical transmission using current experimental models and identify gaps in knowledge that need to be addressed. We further propose novel experimental strategies to address such limitations. url: https://doi.org/10.3389/fimmu.2020.02070 doi: 10.3389/fimmu.2020.02070 id: cord-283505-ousbar6c author: Horman, William S. J. title: The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection date: 2020-09-24 words: 5896.0 sentences: 266.0 pages: flesch: 45.0 cache: ./cache/cord-283505-ousbar6c.txt txt: ./txt/cord-283505-ousbar6c.txt summary: To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. In this study, we aimed to examine the ferret immune response to H7N9 influenza virus infection by analyzing leukocyte population variation associated with disease pathogenesis. While the day 6 ferret which showed worsened disease progression did exhibit the most severe lung pathology, the lack of viral antigen in and around these lesions (Supplementary Figure 1) means they cannot conclusively be classified as being caused by the influenza infection, and thus we are hesitant to classify disease presentation in this ferret as like a high pathogenicity infection based on the histopathology findings regardless of the increase in clinical signs. Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses abstract: As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater disease severity in mammalian hosts compared to natural avian hosts, though the exact mechanisms underlying this are somewhat unclear. Knowledge of the H7N9 host-pathogen interactions have mainly been constrained to natural sporadic human infections. To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. Intriguingly, we observed variable disease outcomes when ferrets were inoculated with the A/Anhui/1/2013 (H7N9) strain. We observed relatively reduced antigen-presenting cell activation in lymphoid tissues which may be correlative with increased disease severity. Additionally, depletions in CD8(+) T cells were not apparent in sick animals. This study provides further insight into the ways that lymphocytes maturate and traffic in response to H7N9 infection in the ferret model. url: https://www.ncbi.nlm.nih.gov/pubmed/33072098/ doi: 10.3389/fimmu.2020.559113 id: cord-296033-5zyoddl7 author: Hu, Xiaoliang title: Transmissible Gastroenteritis Virus Papain-Like Protease 1 Antagonizes Production of Interferon-β through Its Deubiquitinase Activity date: 2017-10-23 words: 3357.0 sentences: 201.0 pages: flesch: 49.0 cache: ./cache/cord-296033-5zyoddl7.txt txt: ./txt/cord-296033-5zyoddl7.txt summary: Coronaviruses (CoVs), such as human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome CoV (SARS-CoV), murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), encode papain-like (PL) proteases that inhibit Sendai virus(SeV-) induced interferon (IFN-β) production. Furthermore, TGEV PL1 exerted deubiquitinase (DUB) activity which strongly inhibited the retinoic acid-induced gene I(RIG-1-) and stimulator of interferon gene(STING-) dependent IFN expression. In the present study, we found that TGEV PL1 encoded by the replicase gene could suppress the IFN-expression and inhibit the nuclear translocation of interferon regulatory factor 3 (IRF3) and exerted deubiquitinase (DUB) activity which strongly inhibited the retinoic acid-induced gene I-(RIG-1-) and stimulator of interferon gene-(STING-) dependent IFN expression. We observed the inhibition of SeV-induced IFN-promoter activation in the presence of PL1, similar to the antagonistic function of NL63 PLP2 and porcine epidemic diarrhea virus (PEDV) PLP2, clearly indicating that TGEV PL1 could act as an interferon antagonist. abstract: Coronaviruses (CoVs), such as human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome CoV (SARS-CoV), murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), encode papain-like (PL) proteases that inhibit Sendai virus- (SeV-) induced interferon (IFN-β) production. Recently, the crystal structure of transmissible gastroenteritis virus (TGEV) PL1 has been solved, which was similar to that of SARS-CoV PL2(pro), which may antagonize host innate immunity. However, very little is known about whether TGEV PL1 can antagonize host innate immune response. Here, we presented evidence that TGEV PL1 encoded by the replicase gene could suppress the IFN-β expression and inhibit the nuclear translocation of interferon regulatory factor 3 (IRF3). The ability to antagonize IFN-β production was dependent on the intact catalytic activity of PL1. Furthermore, TGEV PL1 exerted deubiquitinase (DUB) activity which strongly inhibited the retinoic acid-induced gene I- (RIG-1-) and stimulator of interferon gene- (STING-) dependent IFN expression. Our data collectively suggest that TGEV PL1 can inhibit the IFN-β expression and interfere with RIG-1- and STING-mediated signaling through a viral DUB activity. Our study has yielded strong evidence for the TGEV PL1 mechanisms that counteract the host innate immunity. url: https://doi.org/10.1155/2017/7089091 doi: 10.1155/2017/7089091 id: cord-002937-7xauocti author: Huang, Chung-Guei title: A pilot study on primary cultures of human respiratory tract epithelial cells to predict patients’ responses to H7N9 infection date: 2018-02-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Avian influenza A(H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. We aimed to investigate whether primary cultures of human respiratory tract epithelial cells are helpful to understand H7N9 virus pathogenesis and tissue tropism, and to evaluate how patient-related characteristics can affect the host's response to infection. Normal human bronchial epithelial cells (isolated from two different donors) and primary epithelial cells (harvested from 27 patients undergoing airway surgery) were experimentally infected with H7N9 and/or H1N1pdm for 72 h. After virus infection, the culture media were collected for viral RNA quantitation and cytokine detection. Both H7N9 and H1N1pdm viruses replicated and induced a cytokine response differently for each donor in the normal human bronchial epithelial model. H7N9 replicated equivalently in epithelial cells harvested from the inferior turbinate and paranasal sinus, and those from the larynx and bronchus, at 72 h post-infection. Viral RNA quantity at 72 h was significantly higher in patients aged 21–64 years than in patients aged ≥ 65 years; however, no effects of sex, medical comorbidities, and obesity were noted. H7N9-infected cultured cells released multiple cytokines within 72 h. Levels of interleukin-1β, interleukin-6, interleukin-8, interferon-γ, and tumor necrosis factor-α were associated differently with patient-related characteristics (such as age, sex, obesity, and medical comorbidities). In the era of precision medicine, these findings illustrate the potential utility of this primary culture approach to predict a host's response to H7N9 infection or to future infection by newly emerging viral infections, and to dissect viral pathogenesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865685/ doi: 10.18632/oncotarget.24537 id: cord-023407-s85g7g0x author: Huang, Y.‐M. title: Anti‐Inflammatory Liver X Receptors and Related Molecules in Multiple Sclerosis Patients from Sardinia and Sweden date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The nuclear receptor heterodimers of liver X receptors (LXRs) are recently identified as key transcriptional regulators of genes involved in lipid homeostasis and inflammation. LXRs and their ligands are negative regulators of macrophage inflammatory gene expression. Multiple sclerosis (MS), a demyelinating disease of the central nervous system of unknown cause, is characterized by recurrent inflammation involving macrophages and their inflammatory mediators. Sweden belongs to the countries with a high MS incidence. In Italy, incidence is lower, with an exception for Sardinia where the incidence is even higher than that in Sweden. Subjects from Sardinia are ethnically more homogeneous and differ from Swedes, also regarding genetic background and environment. We studied LXRs and their related molecules of blood mononuclear cells (MNCs) from female patients with untreated relapsing‐remitting MS from Sassari, Sardinia and Stockholm, Sweden. Sex‐ and age‐matched healthy controls (HCs) were from both areas. mRNA expression was evaluated by real‐time PCR. LXR‐α was lower (P < 0.05) in MS (mean ± SEM: 3.1 ± 0.2; n = 37) compared to HC (3.6 ± 0.1; n = 37). LXR‐α was lower in MS from Stockholm (2.6 ± 0.2; n = 22) compared to corresponding HC (3.4 ± 0.1; n = 22; P < 0.01) and compared to MS (3.8 ± 0.2; n = 15; P < 0.001) and HC (4 ± 0.2; n = 15; P < 0.001) from Sardinia. MS patients from Stockholm, but not from Sassari, also expressed lower (P < 0.05) LXR‐β (−4.1 ± 0.4) compared to corresponding HC (−2.9 ± 0.3). MS from Stockholm was associated with higher ABCA‐1 (6.1 ± 0.4 versus 5.0 ± 0.3; P < 0.05) and higher estrogen receptor‐β‐Cx (2.4 ± 0.4 versus 0.8 ± 0.4; P < 0.01) compared to corresponding HC. The HC from Sassari had higher androgen receptor (2.9 ± 0.2) compared to MS from Sassari (1.4 ± 0.3; P < 0.01), MS (1.3 ± 0.4; P < 0.01) and HC from Stockholm (1.2 ± 0.3; P < 0.01). MS from Sassari had lower cyclooxygenase‐1 compared to corresponding HC (5.1 ± 0.4 versus 6.6 ± 0.3; P < 0.01) and lower prostaglandin‐E (−0.03 ± 0.5) compared to the HC (1.4 ± 0.5; P < 0.05) and MS (2.7 ± 0.4; P < 0.05) and HC from Stockholm (1.9 ± 0.4, P < 0.001). Our findings identify LXRs and their related molecules as being involved in MS from Stockholm but not from Sassari, while sex hormone receptors seem to be involved in MS in Sassari. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169544/ doi: 10.1111/j.0300-9475.2004.01423d.x id: cord-351532-2yd4wg9v author: Huang, Yin-Qiu title: No Statistically Apparent Difference in Antiviral Effectiveness Observed Among Ribavirin Plus Interferon-Alpha, Lopinavir/Ritonavir Plus Interferon-Alpha, and Ribavirin Plus Lopinavir/Ritonavir Plus Interferon-Alpha in Patients With Mild to Moderate Coronavirus Disease 2019: Results of a Randomized, Open-Labeled Prospective Study date: 2020-07-14 words: 5739.0 sentences: 260.0 pages: flesch: 48.0 cache: ./cache/cord-351532-2yd4wg9v.txt txt: ./txt/cord-351532-2yd4wg9v.txt summary: title: No Statistically Apparent Difference in Antiviral Effectiveness Observed Among Ribavirin Plus Interferon-Alpha, Lopinavir/Ritonavir Plus Interferon-Alpha, and Ribavirin Plus Lopinavir/Ritonavir Plus Interferon-Alpha in Patients With Mild to Moderate Coronavirus Disease 2019: Results of a Randomized, Open-Labeled Prospective Study The proportion of patients with SARS-CoV-2 nucleic acid negativity in the LPV/r+IFN-α-treated group (61.1%) was higher than the RBV+ IFN-α-treated group (51.5%) and the RBV+LPV/r+IFN-α-treated group (46.9%) at day 14; however, the difference between these groups was calculated to be statistically insignificant. The office of National Health Commission of the People''s Republic of China, and the National Administration Bureau of Traditional Chinese Medicine have jointly issued different versions of the "Guidelines for diagnosis and treatment of novel coronavirus pneumonia", in which LPV/r, IFNa, and RBV are recommended for on-trial use in patients with COVID-19. abstract: BACKGROUND: Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, causing an unprecedented pandemic. However, there is no specific antiviral therapy for coronavirus disease 2019 (COVID-19). We conducted a clinical trial to compare the effectiveness of three antiviral treatment regimens in patients with mild to moderate COVID-19. METHODS: This was a single-center, randomized, open-labeled, prospective clinical trial. Eligible patients with mild to moderate COVID-19 were randomized into three groups: ribavirin (RBV) plus interferon-α (IFN-α), lopinavir/ritonavir (LPV/r) plus IFN-α, and RBV plus LPV/r plus IFN-α at a 1:1:1 ratio. Each patient was invited to participate in a 28-d follow-up after initiation of an antiviral regimen. The outcomes include the difference in median interval to SARS-CoV-2 nucleic acid negativity, the proportion of patients with SARS-CoV-2 nucleic acid negativity at day 14, the mortality at day 28, the proportion of patients re-classified as severe cases, and adverse events during the study period. RESULTS: In total, we enrolled 101 patients in this study. Baseline clinical and laboratory characteristics of patients were comparable among the three groups. In the analysis of intention-to-treat data, the median interval from baseline to SARS-CoV-2 nucleic acid negativity was 12 d in the LPV/r+IFN-α-treated group, as compared with 13 and 15 d in the RBV+IFN-α-treated group and in the RBV+LPV/r+ IFN-α-treated group, respectively (p=0.23). The proportion of patients with SARS-CoV-2 nucleic acid negativity in the LPV/r+IFN-α-treated group (61.1%) was higher than the RBV+ IFN-α-treated group (51.5%) and the RBV+LPV/r+IFN-α-treated group (46.9%) at day 14; however, the difference between these groups was calculated to be statistically insignificant. The RBV+LPV/r+IFN-α-treated group developed a significantly higher incidence of gastrointestinal adverse events than the LPV/r+ IFN-α-treated group and the RBV+ IFN-α-treated group. CONCLUSIONS: Our results indicate that there are no significant differences among the three regimens in terms of antiviral effectiveness in patients with mild to moderate COVID-19. Furthermore, the combination of RBV and LPV/r is associated with a significant increase in gastrointestinal adverse events, suggesting that RBV and LPV/r should not be co-administered to COVID-19 patients simultaneously. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, ID: ChiCTR2000029387. Registered on January 28, 2019. url: https://www.ncbi.nlm.nih.gov/pubmed/32765274/ doi: 10.3389/fphar.2020.01071 id: cord-048485-b8xb1f12 author: Hulst, Marcel title: Early transcriptional response in the jejunum of germ-free piglets after oral infection with virulent rotavirus date: 2008-06-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Germ-free piglets were orally infected with virulent rotavirus to collect jejunal mucosal scrapings at 12 and 18 hours post infection (two piglets per time point). IFN-gamma mRNA expression was stimulated in the mucosa of all four infected piglets, indicating that they all responded to the rotavirus infection. RNA pools prepared from two infected piglets were used to compare whole mucosal gene expression at 12 and 18 hpi to expression in uninfected germ-free piglets (n = 3) using a porcine intestinal cDNA microarray. Microarray analysis identified 13 down-regulated and 17 up-regulated genes. Northern blot analysis of a selected group of genes confirmed the data of the microarray. Genes were functionally clustered in interferon-regulated genes, proliferation/differentiation genes, apoptosis genes, cytoskeleton genes, signal transduction genes, and enterocyte digestive, absorptive, and transport genes. Down-regulation of the transport gene cluster reflected in part the loss of rotavirus-infected enterocytes from the villous tips. Data mining suggested that several genes were regulated in lower- or mid-villus immature enterocytes and goblet cells, probably to support repair of the damaged epithelial cell layer at the villous tips. Furthermore, up-regulation was observed for IFN-γ induced guanylate binding protein 2, a protein that effectively inhibited VSV and EMCV replication in vitro (Arch Virol 150:1213–1220, 2005). This protein may play a role in the small intestine’s innate defense against enteric viruses like rotavirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-008-0118-6) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441536/ doi: 10.1007/s00705-008-0118-6 id: cord-023387-tyeh14wz author: Hvas, C. L. title: Probiotic Bacteria Induce Regulatory Cytokine Production via Dendritic Cells date: 2008-06-28 words: 16893.0 sentences: 881.0 pages: flesch: 46.0 cache: ./cache/cord-023387-tyeh14wz.txt txt: ./txt/cord-023387-tyeh14wz.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Probiotic bacteria, e.g. Lactobacillus spp., may improve diseases such as chronic inflammatory bowel disease. We examined cytokine production and phenotypic change after in vitro stimulation of T cells from healthy volunteers using different probiotic strains. Methods: T cells were cultured from colonic biopsies from eight healthy volunteers (Agnholt and Kaltoft, Exp Clin Immunogenet 2001;18:213–25), and dendritic cells were matured from their peripheral blood mononuclear cells. T‐cell cultures were stimulated with autologous bacterial sonicate or strains of Lactobacillus spp., with and without the addition of dendritic cells. Cytokine levels (TNF‐α, IFN‐γ, IL‐10 and GM‐CSF) and phenotype (CD3, CD4, CD25 and CD69) were measured on day 4. Results: Lactobacillus spp. induced higher productions of TNF‐α and IL‐10 than did autologous bacteria. In presence of dendritic cells, the production of all cytokines increased. However, the increases of IFN‐γ and TNF‐α were more pronounced in wells with autologous bacteria than in wells with Lactobacillus spp. The addition of dendritic cells upregulated CD25 expression without simultaneous upregulation of CD69. The upregulation was pronounced after stimulation with Lactobacillus rhamnosus GG compared with autologous bacteria and other lactobacilli. Discussion: In presence of dendritic cells, autologous bacteria induced inflammatory cytokines, while probiotics mainly induced regulatory cytokines. Lactobacillus rhamnosus GG induced a regulatory phenotype (cd25(+)), in part mediated by dendritic cells. Future studies will address whether this shift to a CD25(+) phenotype represents a differentiation into competent regulatory T cells. In a clinical context, such cells might be used for treatment of inflammatory diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169507/ doi: 10.1111/j.0300-9475.2004.01423au.x id: cord-276587-ynionj5r author: Hwang, Mihyun title: Alpha/Beta Interferon (IFN-α/β) Signaling in Astrocytes Mediates Protection against Viral Encephalomyelitis and Regulates IFN-γ-Dependent Responses date: 2018-04-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The contribution of distinct central nervous system (CNS) resident cells to protective alpha/beta interferon (IFN-α/β) function following viral infections is poorly understood. Based on numerous immune regulatory functions of astrocytes, we evaluated the contribution of astrocyte IFN-α/β signaling toward protection against the nonlethal glia- and neuronotropic mouse hepatitis virus (MHV) strain A59. Analysis of gene expression associated with IFN-α/β function, e.g., pattern recognition receptors (PRRs) and interferon-stimulated genes (ISGs), revealed lower basal mRNA levels in brain-derived astrocytes than in microglia. Although astrocytes poorly induced Ifnβ mRNA following infection, they upregulated various mRNAs in the IFN-α/β pathway to a higher extent than microglia, supporting effective IFN-α/β responsiveness. Ablation of the IFN-α/β receptor (IFNAR) in astrocytes using mGFAPcre IFNAR(fl/fl) mice resulted in severe encephalomyelitis and mortality, coincident with uncontrolled virus replication. Further, virus spread was not restricted to astrocytes but also affected microglia and neurons, despite increased and sustained Ifnα/β and ISG mRNA levels within the CNS. IFN-γ, a crucial mediator for MHV control, was not impaired in infected mGFAPcre IFNAR(fl/fl) mice despite reduced T cell CNS infiltration. Unexpectedly however, poor induction of IFN-γ-dependent major histocompatibility complex (MHC) class II expression on microglia supported that defective IFN-γ signaling contributes to uncontrolled virus replication. A link between sustained elevated IFN-α/β and impaired responsiveness to IFN-γ supports the novel concept that temporally limited early IFN-α/β responses are critical for effective antiviral IFN-γ function. Overall, our results imply that IFN-α/β signaling in astrocytes is not only critical in limiting early CNS viral spread but also promotes protective antiviral IFN-γ function. IMPORTANCE An antiviral state established by IFN-α/β contains initial viral spread as adaptive immunity develops. While it is apparent that the CNS lacks professional IFN-α/β producers and that resident cells have distinct abilities to elicit innate IFN-α/β responses, protective interactions between inducer and responder cells require further investigation. Infection with a glia- and neuronotropic coronavirus demonstrates that astrocytes mount a delayed but more robust response to infection than microglia, despite their lower basal mRNA levels of IFN-α/β-inducing components. Lethal, uncontrolled viral dissemination following ablation of astrocyte IFN-α/β signaling revealed the importance of IFN-α/β responses in a single cell type for protection. Sustained global IFN-α/β expression associated with uncontrolled virus did not suffice to protect neurons and further impaired responsiveness to protective IFN-γ. The results support astrocytes as critical contributors to innate immunity and the concept that limited IFN-α/β responses are critical for effective subsequent antiviral IFN-γ function. url: https://doi.org/10.1128/jvi.01901-17 doi: 10.1128/jvi.01901-17 id: cord-304457-8g36h1bz author: Idelsis, E.-M. title: Effect and safety of combination of interferon alpha-2b and gamma or interferon alpha-2b for negativization of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial. date: 2020-08-01 words: 5862.0 sentences: 330.0 pages: flesch: 47.0 cache: ./cache/cord-304457-8g36h1bz.txt txt: ./txt/cord-304457-8g36h1bz.txt summary: Conclusions: In a cohort of 63 hospitalized patients between 19 to 82 years-old with positive SARS-CoV-2, HeberFERON significantly negativized the virus on day 4 of treatment when comparing with IFN-alpha2b. The RT-PCR after treatment with IFNs on day 14 for hospital discharges was negative to SARS-CoV-2 in 100% and 91% of patients of HeberFERON and control cohorts, respectively. These results confirm the validity of early intervention with the treatment of IFNs in patients with COVID-19, whereas demonstrated in the trial, the combination of type I and type II IFNs impacts strongly in the reduction of the risk for a severe disease likely through the efficient implementation of a timely controlled inflammatory antiviral response against the SARS-CoV-2 infection. Evaluation of the Effect and Safety of HeberFERON vs Heberon Alpha in Patients Infected with Corona Virus SARS-CoV-2 (Study ESPERANZA/HOPE): TRIALS abstract: Abstract Objectives: IFN-alpha2b and IFN-gamma combination has demonstrated favorable pharmacodynamics for genes underlying antiviral activity which might be involved in the defense of the organism from a SARS-CoV-2 infection. Considering this we conducted a randomized controlled clinical trial for efficacy and safety evaluation of subcutaneous IFN-alpha2b and IFN-gamma administration in patients positive to SARS-CoV-2. Methods: We enrolled 19-82 years-old inpatients at the Military Central Hospital Luis Diaz Soto, Havana, Cuba. They were hospitalized after confirmed diagnosis for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Patients were randomly assigned in a 1:1 ratio to receive either, subcutaneous treatment with a co-lyophilized combination of 3.0 MIU IFN-alpha2b and 0.5 MIU IFN-gamma (HeberFERON, CIGB, Havana, Cuba), twice a week for two weeks, or thrice a week intramuscular injection of 3.0 MIU IFN-alpha2b (Heberon Alpha R, CIGB, Havana, Cuba). Additionally, all patients received lopinavir-ritonavir 200/50 mg every 12 h and chloroquine 250 mg every 12 h (standard of care). The primary endpoints were the time to negativization of viral RNA and the time to progression to severe COVID-19, from the start of treatment. The protocol was approved by the Ethics Committee on Clinical Investigation from the Hospital and the Center for the State Control of Medicines, Equipment and Medical Devices in Cuba. Informed consent was obtained from each participant. Results: A total of 79 patients with laboratory-confirmed SARS-CoV-2 infection, including symptomatic or asymptomatic conditions, fulfilled the inclusion criteria and underwent randomization. Thirty-three subjects were assigned to the HeberFERON group, and 33 to the Heberon Alpha R group. Sixty-three patients were analyzed for viral negativization, of them 78.6% in the HeberFERON group negativized the virus after 4 days of treatment versus 40.6% of patients in the Heberon Alpha R groups (p=0.004). Time to reach the negativization of the SARS-CoV-2 measured by RT-PCR in real time was of 3.0 and 5.0 days for the HeberFERON and Heberon Alpha R groups, respectively. A significant improvement in the reduction of time for negativization was attributable to HeberFERON (p=0.0027, Log-rank test) with a Hazard Ratio of 3.2 and 95% CI of 1.529 to 6.948, as compared to Heberon Alpha R treated group. Worsening of respiratory symptoms was detected in two (6.6%) and one (3.3%) patients in HeberFERON and IFN-alpha2b groups, respectively. None of the subjects transit to severe COVID-19 during the study or the epidemiological follow-up for 21 more days. RT-PCR on day 14 after the start of the treatment was negative to SARS-CoV-2 in 100% and 91% of patients of the combination of IFNs and IFN-alpha2b, respectively. Negativization for HeberFERON treated patients was related to a significant increase in lymphocytes counts and an also significant reduction in CRP as early as 7 days after commencing the therapeutic schedule. All the patients in both cohorts recover by day 14 and were in asymptomatic condition and laboratory parameters return to normal values by day 14 after treatment initiation. Adverse events were identified in 31.5% of patients, 28.5% in the control group, and 34.4% in the HeberFERON group, and the most frequent were headaches (17.4%). Conclusions: In a cohort of 63 hospitalized patients between 19 to 82 years-old with positive SARS-CoV-2, HeberFERON significantly negativized the virus on day 4 of treatment when comparing with IFN-alpha2b. Heberon Alpha R also showed efficacy for the treatment of the viral infection. Both treatments were safe and positively impact on the resolution of the symptoms. None of the patients developed severe COVID-19. Key words: COVID-19, treatment, drug, virus negativization, antiviral, interferon combination, SARS CoV-2. url: https://doi.org/10.1101/2020.07.29.20164251 doi: 10.1101/2020.07.29.20164251 id: cord-337285-t6qr41wc author: Ikeda, Masanori title: Modulation of host metabolism as a target of new antivirals() date: 2007-10-10 words: 8180.0 sentences: 466.0 pages: flesch: 46.0 cache: ./cache/cord-337285-t6qr41wc.txt txt: ./txt/cord-337285-t6qr41wc.txt summary: Using cell culture systems, several cellular proteins have been identified as effective molecules for HCV RNA replication (Table 1) . [66] reported that lovastatin (LOV), one of the HMG-CoA reductase inhibitors, inhibited HCV RNA replication in HCV replicon-harboring cells. Depletion of the GGPP by statins may inhibit the geranylgeranylation of cellular proteins such as FBL2 and cause the anti-HCV effect in the cells. During the development of IFN therapy for patients with CH-C, the lack of a robust method of HCV RNA replication in cell culture has hampered research into the HCV life cycle and the discovery of potent new anti-HCV reagents. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells abstract: The therapy for chronic hepatitis C (CH–C) started with interferon (IFN) monotherapy in the early 1990s and this therapy was considered effective in about 10% of cases. The present standard therapy of pegylated IFN with ribavirin achieves a sustained virologic response in about 50% of patients. However, about half of the CH–C patients are still at risk of fatal liver cirrhosis and hepatocellular carcinoma. The other significant event in hepatitis C virus (HCV) research has been the development of a cell culture system. The subgenomic replicon system enables robust HCV RNA replication in hepatoma cells. And recently, the complete life cycle of HCV has been achieved using a genotype 2a strain, JFH1. These hallmarks have provided much information about the mechanisms of HCV replication, including information on the host molecules required for the replication. Anti-HCV reagents targeting HCV proteins have been developed, and some of them are now in clinical trials. However, the RNA-dependent RNA polymerase frequently causes mutations in the HCV genome, which lead to the emergence of drug-resistant HCV mutants. Some of the cellular proteins essential for HCV RNA replication have already been discovered using the HCV cell culture system. These host molecules are also candidate targets for antivirals. Here, we describe the recent progress regarding the anti-HCV reagents targeting host metabolism. url: https://www.sciencedirect.com/science/article/pii/S0169409X07001317 doi: 10.1016/j.addr.2007.03.021 id: cord-346836-6jyv0q5e author: Ikegami, Tetsuro title: The Pathogenesis of Rift Valley Fever date: 2011-05-06 words: 10419.0 sentences: 483.0 pages: flesch: 46.0 cache: ./cache/cord-346836-6jyv0q5e.txt txt: ./txt/cord-346836-6jyv0q5e.txt summary: RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis. RVFV infection in humans primarily causes a self-limiting febrile illness; however, some patients develop hemorrhagic fever, neurological disorders, or blindness after the febrile period [5, 7, 8] . Inbred rat strains mimic the disparate human response to rift valley fever virus infection Clinical, virological and serological response of the west african dwarf sheep to experimental infection with different strains of rift valley fever virus abstract: Rift Valley fever (RVF) is an emerging zoonotic disease distributed in sub-Saharan African countries and the Arabian Peninsula. The disease is caused by the Rift Valley fever virus (RVFV) of the family Bunyaviridae and the genus Phlebovirus. The virus is transmitted by mosquitoes, and virus replication in domestic ruminant results in high rates of mortality and abortion. RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/21666766/ doi: 10.3390/v3050493 id: cord-325624-6anybxnk author: Ireland, Derek D. C. title: RNase L Mediated Protection from Virus Induced Demyelination date: 2009-10-02 words: 8082.0 sentences: 397.0 pages: flesch: 43.0 cache: ./cache/cord-325624-6anybxnk.txt txt: ./txt/cord-325624-6anybxnk.txt summary: The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. RNase L specifically protected the brain stem from sustained infection and prevented spread of virus to microglia/macrophages located in spinal cord grey matter. The increased pathological changes in both brain stem and spinal cord thus correlated with the high mortality rates of RL 2/2 mice starting at day 9 p.i. The inability to directly link increased axonal damage with enhanced neuronal infection remains puzzling and supports dysregulation of oligodendrocyte function and/or neuroprotective functions of microglia as contributing factors to the severe pathological phenotype and clinical outcome. Numerous functions of RNase L, not directly associated with anti-viral activity, may contribute to the increased susceptibility of RL 2/2 mice to MHV-JHM infection. abstract: IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(−/−)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination. url: https://www.ncbi.nlm.nih.gov/pubmed/19798426/ doi: 10.1371/journal.ppat.1000602 id: cord-023394-ptfjxpo6 author: Isa, A. title: Mapping of the Ex Vivo Cellular Immune Response Against the Complete Human Parvovirus B19 Genome During Acute Infection date: 2008-06-28 words: 16904.0 sentences: 872.0 pages: flesch: 46.0 cache: ./cache/cord-023394-ptfjxpo6.txt txt: ./txt/cord-023394-ptfjxpo6.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Background: Human parvovirus B19 (B19) is a ubiquitous pathogen, normally causing a mild self‐limiting disease, but also capable of causing both significant pathology and long‐term persistence. The small size and stability of the virus makes it suitable for mapping of the full breath and the kinetics of the cellular immune responses following acute viral infection. Methods: Five patients with acute primary B19 infection were included in the study and followed consecutively for up to 200 weeks. Cellular immune responses were mapped by IFNγ enzyme‐linked immunospot to overlapping peptides spanning the whole B19 genome. Results: In all five acutely infected patients, we were able to monitor the kinetics of a strong specific cellular immune reaction. Responses peaked at levels of 850–1850 SFC/million PBMCs, roughly corresponding to 0.3–0.6% B19‐specific CD8(+) cells circulating in peripheral blood at 10–80 weeks post‐infection. The responses in individual patients were directed to three or four different peptide pools, and the specificity was confined to the same CD8 epitopes present in the pools throughout the follow‐up period. The majority of responses were directed to the virus nonstructural protein, only two patients showed any response to the capsid proteins, elicited by the same epitope in both cases. Conclusion: The cellular immune responses to acute B19 infection are surprisingly narrow in distribution and remain at high levels for up to 80 weeks post‐infection. The initial epitope specificity is maintained, and the majority of responses target the virus nonstructural protein, which is not included in vaccine preparations, evaluated against the infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169519/ doi: 10.1111/j.0300-9475.2004.01423n.x id: cord-347200-dtwhd6zy author: Ivanova, Daria title: NK Cells in Mucosal Defense against Infection date: 2014-08-14 words: 6955.0 sentences: 369.0 pages: flesch: 49.0 cache: ./cache/cord-347200-dtwhd6zy.txt txt: ./txt/cord-347200-dtwhd6zy.txt summary: Mucosal NK cells play a pivotal role in early protection through their cytolytic function and IFNγ production against bacteria, fungi, viruses, and parasitic infections. Since NK precursors and other ILC populations in secondary lymphoid tissues express varying levels of this integrin, it may be possible that an NK-DC interaction is a requirement for immature NK cells to be signaled to home to mucosal sites. During mucosal infections of humans and mice, NK cells are recruited to sites of infection and play an important role in immune defense [6, 48] . Therefore the cytokine milieu present in the different mucosal tissues in addition to activating signals stimulated that by diverse pathogens help NK cells respond to infection. NK cells in humans are also important for innate control of gut mucosal infections. During infection, resident mucosal tissue NK cells respond primarily through IFN production, which contributes directly to early control of pathogens. abstract: Conventional natural killer cells (NK cells) provide continual surveillance for cancer and rapid responses to infection. They develop in the bone marrow, emerge as either NK precursor cells, immature, or mature cells, and disperse throughout the body. In the periphery NK cells provide critical defense against pathogens and cancer and are noted to develop features of adaptive immune responses. In the tightly regulated and dynamic mucosal tissues, they set up residency via unknown mechanisms and from sources that are yet to be defined. Once resident, they appear to have the ability to functionally mature dependent on the mucosal tissue microenvironment. Mucosal NK cells play a pivotal role in early protection through their cytolytic function and IFNγ production against bacteria, fungi, viruses, and parasitic infections. This review presents what is known about NK cell development and phenotypes of mucosal tissue resident conventional NK cells. The question of how they come to reside in their tissues and published data on their function against pathogens during mucosal infection are discussed. Dissecting major questions highlighted in this review will be important to the further understanding of NK cell homing and functional diversity and improve rational design of NK cell based therapies against mucosal infection. url: https://doi.org/10.1155/2014/413982 doi: 10.1155/2014/413982 id: cord-003315-r1wkx0ml author: Jacobs, Sophie title: Species Specificity of Type III Interferon Activity and Development of a Sensitive Luciferase-Based Bioassay for Quantitation of Mouse Interferon-λ date: 2018-11-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The type III interferon (IFN-λ) family includes 4 IFN-λ subtypes in man. In the mouse, only the genes coding for IFN-λ2 and -λ3 are present. Unlike mouse and human type I IFNs (IFN-α/β), which exhibit strong species specificity, type III IFNs were reported to act in a cross-specific manner. We reexamined the cross-specificity and observed that mouse and human IFN-λ exhibit some species specificity, although much less than type I IFNs. Mouse IFN-λ3 displayed clear species specificity, being 25-fold less active in human cells than the closely related mouse IFN-λ2. This specificity likely depends on amino acids in α helices A and F that diverged from other IFN-λ sequences. Human IFN-λ4, in contrast, retained high activity in mouse cells. We next developed a firefly luciferase-based reporter cell line, named Fawa-λ-luc, to detect IFN-λ in biological fluids with high specificity and sensitivity. Fawa-λ-luc cells, derived from mouse epithelial cells that are responsive to IFN-λ, were made nonresponsive to type I IFNs by inactivation of the Ifnar2 gene and strongly responsive to IFN-λ by overexpression of the mouse IFNLR1. This bioassay was as sensitive as a commercially available enzyme-linked immunosorbent assay in detecting mouse IFN-λ in cell culture supernatant, as well as in serum and bronchoalveolar lavage samples of virus-infected mice. The assay also enabled the sensitive detection of human IFN-λ activity, including that of the divergent IFN-λ4 with a bias, however, due to variable activity of IFN-λ subtypes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249671/ doi: 10.1089/jir.2018.0066 id: cord-266679-gs1k7263 author: Jacques, Alexandre title: A synergistic interferon-γ production is induced by mouse hepatitis virus in interleukin-12 (IL-12)/IL-18-activated natural killer cells and modulated by carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1a receptor date: 2009-09-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The production of interferon-γ (IFN-γ) by infiltrating natural killer (NK) cells in liver is involved in the control of mouse hepatitis virus (MHV) infection. The objectives of this study were to identify the mechanisms used by MHV type 3 to modulate the production of IFN-γ by NK cells during the acute hepatitis in susceptible C57BL/6 mice. Ex vivo and in vitro experiments revealed that NK cells, expressing carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1a (the MHV receptor), can produce a higher level of IFN-γ in the presence of both L2-MHV3 and interleukin-12 (IL-12)/IL-18. The synergistic production of IFN-γ by NK cells depends on viral replication rather than viral fixation only, because it is inhibited or not induced in cells infected with ultraviolet-inactivated viruses and in cells from Ceacam1a(−/−) mice infected with virulent viruses. The synergistic IFN-γ production involves the p38 mitogen-activated protein kinase (MAPK) rather than the extracellular signal-regulated kinase-1/2 MAPK signalling pathway. However, the signal triggered through the engagement of CEACAM1a decreases the production of IFN-γ, when these molecules are cross-linked using specific monoclonal antibodies. These results suggest that control of acute hepatitis by IFN-γ-producing NK cells may depend on both production of IL-12 and IL-18 in the liver environment and viral infection of NK cells. url: https://doi.org/10.1111/j.1365-2567.2008.03030.x doi: 10.1111/j.1365-2567.2008.03030.x id: cord-303893-47lxq8pi author: Jalkanen, Juho title: Interferon beta-1a for COVID-19: critical importance of the administration route date: 2020-06-12 words: 1276.0 sentences: 70.0 pages: flesch: 45.0 cache: ./cache/cord-303893-47lxq8pi.txt txt: ./txt/cord-303893-47lxq8pi.txt summary: Interferon beta-1a for COVID-19: critical importance of the administration route Juho Jalkanen 1 , Maija Hollmén 2 and Sirpa Jalkanen 2* Type I interferons, especially IFN-beta, have been appointed as potential leading therapeutics to tackle severe COVID-19 and are currently being evaluated in REMAP-CAP and the WHO''s Solidarity Trial. We wish to highlight the differences of these two treatment methods and also other crucial aspects of IFN-beta treatment for COVID-19 and acute respiratory distress syndrome (ARDS). Nonetheless, the purpose of i.v. administered IFN-beta for the treatment of COVID-19 and ARDS is to maximise bioavailability of the drug at the lung vasculature, as well as other vascular beds. There are a limited number of direct studies on the timing of immunomodulatory treatments such as IFN-beta, but given our basic understanding of human biology and viral defence, we suggest that IFN-beta should be given early to COVID-19 patients. abstract: nan url: https://doi.org/10.1186/s13054-020-03048-5 doi: 10.1186/s13054-020-03048-5 id: cord-332688-xqt2aw96 author: Jalkanen, Juho title: Glucocorticoids inhibit type I IFN beta signaling and the upregulation of CD73 in human lung date: 2020-05-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32430515/ doi: 10.1007/s00134-020-06086-3 id: cord-299299-ov6bf1ff author: Janowicz, Anna title: Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8 date: 2015-03-11 words: 7538.0 sentences: 406.0 pages: flesch: 54.0 cache: ./cache/cord-299299-ov6bf1ff.txt txt: ./txt/cord-299299-ov6bf1ff.txt summary: Replication of BTV8(H) was relatively poor in interferon (IFN)-competent primary ovine endothelial cells compared to replication of BTV8(L), and this phenotype was determined by several viral genomic segments, including Seg4 and Seg9. Here, in order to determine the roles played by specific BTV genomic segments in virus adaptation to tissue culture and attenuation in vivo, we compared genetic and phenotypic differences between BTV8 NET2006 minimally passaged in tissue culture, a derivative of this strain extensively passaged in cell culture, and 34 reassortants between the two viruses. Both viruses replicated very efficiently in IFN-deficient CPT-Tert cells, but BTV8 H reached titers approximately 100-fold higher than its parental virus (Fig. 1A) . The data obtained so far indicate that BTV8 H had accumulated mutations that affected virus replication in IFN-competent cells and resulted in attenuation in vivo both in IFNAR Ϫ/Ϫ mice and in sheep. abstract: Bluetongue virus (BTV) causes bluetongue, a major hemorrhagic disease of ruminants. In order to investigate the molecular determinants of BTV virulence, we used a BTV8 strain minimally passaged in tissue culture (termed BTV8(L) in this study) and a derivative strain passaged extensively in tissue culture (BTV8(H)) in in vitro and in vivo studies. BTV8(L) was pathogenic in both IFNAR(−/−) mice and in sheep, while BTV8(H) was attenuated in both species. To identify genetic changes which led to BTV8(H) attenuation, we generated 34 reassortants between BTV8(L) and BTV8(H). We found that partial attenuation of BTV8(L) in IFNAR(−/−) mice was achieved by simply replacing genomic segment 2 (Seg2, encoding VP2) or Seg10 (encoding NS3) with the BTV8(H) homologous segments. Fully attenuated viruses required at least two genome segments from BTV8(H), including Seg2 with either Seg1 (encoding VP1), Seg6 (encoding VP6 and NS4), or Seg10 (encoding NS3). Conversely, full reversion of virulence of BTV8(H) required at least five genomic segments of BTV8(L). We also demonstrated that BTV8(H) acquired an increased affinity for glycosaminoglycan receptors during passaging in cell culture due to mutations in its VP2 protein. Replication of BTV8(H) was relatively poor in interferon (IFN)-competent primary ovine endothelial cells compared to replication of BTV8(L), and this phenotype was determined by several viral genomic segments, including Seg4 and Seg9. This study demonstrated that multiple viral proteins contribute to BTV8 virulence. VP2 and NS3 are primary determinants of BTV pathogenesis, but VP1, VP5, VP4, VP6, and VP7 also contribute to virulence. IMPORTANCE Bluetongue is one of the major infectious diseases of ruminants, and it is listed as a notifiable disease by the World Organization for Animal Health (OIE). The clinical outcome of BTV infection varies considerably and depends on environmental and host- and virus-specific factors. Over the years, BTV serotypes/strains with various degrees of virulence (including nonpathogenic strains) have been described in different geographical locations. However, no data are available to correlate the BTV genotype to virulence. This study shows that BTV virulence is determined by different viral genomic segments. The data obtained will help to characterize thoroughly the pathogenesis of bluetongue. The possibility to determine the pathogenicity of virus isolates on the basis of their genome sequences will help in the design of control strategies that fit the risk posed by new emerging BTV strains. url: https://doi.org/10.1128/jvi.00395-15 doi: 10.1128/jvi.00395-15 id: cord-273122-w9hemznv author: Jans, Jop title: Actin- and clathrin-dependent mechanisms regulate interferon gamma release after stimulation of human immune cells with respiratory syncytial virus date: 2016-03-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Respiratory syncytial virus (RSV) can cause recurrent and severe respiratory tract infections. Cytoskeletal proteins are often involved during viral infections, either for cell entry or the initiation of the immune response. The importance of actin and clathrin dynamics for cell entry and the initiation of the cellular immune response against RSV in human immune cells is not known yet. The aim of this study was to investigate the role of actin and clathrin on cell entry of RSV and the subsequent effect on T cell activation and interferon gamma release in human immune cells. METHODS: Peripheral blood mononuclear cells and purified monocytes were isolated from healthy adults and stimulated in vitro with RSV. Actin and clathrin dynamics were inhibited with respectively cytochalasin D and chlorpromazine. T cell receptor signaling was inhibited with cyclosporin A. Flow cytometry was used to determine the role of actin and clathrin on cell entry and T cell activation by RSV. Enzyme-linked immunosorbent assays were used to investigate the contribution of actin and clathrin on the release of interferon gamma. RESULTS: Cell entry, virus gene transcription and interferon gamma release are actin-dependent. Post-endocytic processes like the increased expression of major histocompatibility complex II on monocytes , T cell activation and the release of interferon gamma are clathrin-dependent. Finally, T cell receptor signaling affects T cell activation, whereas soluble interleukin 18 is dispensable. CONCLUSION: Analysis of cell entry and interferon gamma release after infection with RSV reveals the importance of actin- and clathrin-dependent signaling in human immune cells. Insights into the cellular biology of the human immune response against respiratory syncytial virus will provide a better understanding of disease pathogenesis and may prove useful in the development of preventive strategies. url: https://www.ncbi.nlm.nih.gov/pubmed/27004689/ doi: 10.1186/s12985-016-0506-6 id: cord-334510-37g8zxne author: Jartti, T. title: Distinct regulation of tonsillar immune response in virus infection date: 2014-03-29 words: 4177.0 sentences: 251.0 pages: flesch: 42.0 cache: ./cache/cord-334510-37g8zxne.txt txt: ./txt/cord-334510-37g8zxne.txt summary: OBJECTIVE: To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T‐cell‐ and innate immune response‐specific cytokines, transcription factors, and type I/II/III interferons in human tonsils. Conclusions: Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes. Conclusions: Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes. Studies in adults have shown an association between persistent/latent Abbreviations AdV, adenovirus; BoV, bocavirus-1; CT, cycle threshold; CV, coronavirus; EF1-a, elongation factor-1a; EV, enteroviruses; FOXP3, forkhead box protein 3; Flu, influenza A or B virus; IFN, interferon; IL, interleukin; MPV, metapneumovirus; PBMC, peripheral blood mononuclear cells; PCR, polymerase chain reaction; PIV, parainfluenza virus types 1-4; RORC2, retinoic acid receptor-related orphan receptor C2; RSV, respiratory syncytial virus; RV, rhinovirus; suppl., supplementary; Th, T helper cell; TGF-b, transforming growth factor-b. abstract: BACKGROUND: The relationships between tonsillar immune responses, and viral infection and allergy are incompletely known. OBJECTIVE: To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T‐cell‐ and innate immune response‐specific cytokines, transcription factors, and type I/II/III interferons in human tonsils. METHODS: Palatine tonsil samples were obtained from 143 elective tonsillectomy patients. Adenovirus, bocavirus‐1, coronavirus, enteroviruses, influenza virus, metapneumovirus, parainfluenza virus, rhinovirus, and respiratory syncytial virus were detected using PCR. The mRNA expression levels of IFN‐α, IFN‐β, IFN‐γ, IL‐10, IL‐13, IL‐17, IL‐28, IL‐29, IL‐37, TGF‐β, FOXP3, GATA3, RORC2, and Tbet were directly analyzed by quantitative RT‐PCR. RESULTS: Fifty percentage of subjects reported allergy, 59% had ≥1 nasopharyngeal viruses, and 24% had ≥1 intratonsillar viruses. Tonsillar virus detection showed a strong negative association with age; especially rhinovirus or parainfluenza virus detection showed positive association with IFN‐γ and Tbet expressions. IL‐37 expression was positively associated with atopic dermatitis, whereas IFN‐α, IL‐13, IL‐28, and Tbet expressions were negatively associated with allergic diseases. Network analyses demonstrated strongly polarized clusters of immune regulatory (IL‐10, IL‐17, TGF‐β, FOXP3, GATA3, RORC2, Tbet) and antiviral (IFN‐α, IFN‐β, IL‐28, IL‐29) genes. These two clusters became more distinctive in the presence of viral infection or allergy. A negative correlation between antiviral cytokines and IL‐10, IL‐17, IL‐37, FOXP3, and RORC2 was observed only in the presence of viruses, and interestingly, IL‐13 strongly correlated with antiviral cytokines. CONCLUSIONS: Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes. url: https://www.ncbi.nlm.nih.gov/pubmed/24684577/ doi: 10.1111/all.12396 id: cord-283096-qm7h4qui author: Jeon, Young Joo title: ISG15 and immune diseases date: 2010-02-12 words: 11144.0 sentences: 606.0 pages: flesch: 44.0 cache: ./cache/cord-283096-qm7h4qui.txt txt: ./txt/cord-283096-qm7h4qui.txt summary: Some of them are type I IFN-induced proteins, such as PKR and RIG-I, and some are the key regulators that are involved in IFN signaling, such as JAK1 and STAT1, implicating the role of ISG15 and its conjugates in type I IFN-mediated innate immune responses. Viral infection also strongly induces ISG15 [18, 19] because one of its major host responses is the production of type I IFNs. A number of proteins that are involved in antiviral signaling pathways, including RIG-I, MDA-5, Mx1, PKR, STAT1, and JAK1, have been identified as target proteins for ISGylation. Swiss 3T3 cells expressing constitutively active MKK7-JNK1β fusion protein show increased resistance to apoptosis induced by vesicular stomatitis virus (VSV) infection, suggesting the involvement of JNK signaling pathway in antiviral response. acid seems to elevate the levels of ISG15 and its conjugates by stimulating cells to secrete IFNs. UBE1L is a 112-kDa protein that shows a 45% identity in amino acid sequence to the human ubiquitin-activating E1 enzyme (UBE1) [73] . abstract: ISG15, the product of interferon (IFN)-stimulated gene 15, is the first identified ubiquitin-like protein, consisting of two ubiquitin-like domains. ISG15 is synthesized as a precursor in certain mammals and, therefore, needs to be processed to expose the C-terminal glycine residue before conjugation to target proteins. A set of three-step cascade enzymes, an E1 enzyme (UBE1L), an E2 enzyme (UbcH8), and one of several E3 ligases (e.g., EFP and HERC5), catalyzes ISG15 conjugation (ISGylation) of a specific protein. These enzymes are unique among the cascade enzymes for ubiquitin and other ubiquitin-like proteins in that all of them are induced by type I IFNs or other stimuli, such as exposure to viruses and lipopolysaccharide. Mass spectrometric analysis has led to the identification of several hundreds of candidate proteins that can be conjugated by ISG15. Some of them are type I IFN-induced proteins, such as PKR and RIG-I, and some are the key regulators that are involved in IFN signaling, such as JAK1 and STAT1, implicating the role of ISG15 and its conjugates in type I IFN-mediated innate immune responses. However, relatively little is known about the functional significance of ISG15 induction due to the lack of information on the consequences of its conjugation to target proteins. Here, we describe the recent progress made in exploring the biological function of ISG15 and its reversible modification of target proteins and thus in their implication in immune diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/20153823/ doi: 10.1016/j.bbadis.2010.02.006 id: cord-268438-bjs5oliw author: Jin, Yilin title: Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination date: 2019-12-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: RIG-I-like receptors (RLRs) play important roles in response to virus infection by regulating host innate immune signaling pathways. Meanwhile, the RLR signaling pathway is also tightly regulated by host and virus to achieve the immune homeostasis between antiviral responses and virus survival. Here, we found that zebrafish TRIM25 (zbTRIM25) functioned as a positive regulator of RLR signaling pathway during red spotted grouper nervous necrosis virus (RGNNV) infection. Post-RGNNV infection, zbTRIM25 expression was obviously inhibited and ectopic expression of zbTRIM25 led to enhanced expression of RLR signaling pathway-related genes. Overexpression and knockdown analysis revealed that zbTRIM25 promoted zebrafish RIG-I (zbRIG-I)-mediated IFN signaling and inhibited RGNNV replication. Mechanistically, zbTRIM25 bound to zbRIG-I; in particular, the SPRY domain of zbTRIM25 interacted with the tandem caspase activation and recruitment domains (2CARD) and repressor domain (RD) regions of zbRIG-I. zbTRIM25 promoted the K63 polyubiquitination of 2CARD and RD regions of zbRIG-I. Furthermore, zbTRIM25-mediated zbRIG-I activation of IFN production was enhanced by K63-linked ubiquitin, indicating that zbTRIM25-mediated zbRIG-I polyubiquitination was essential for RIG-I-triggered IFN induction. In conclusion, these findings reveal a novel mechanism that zbTRIM25 positively regulates the innate immune response by targeting and promoting the K63-linked polyubiquitination of zbRIG-I. url: https://www.ncbi.nlm.nih.gov/pubmed/31849979/ doi: 10.3389/fimmu.2019.02805 id: cord-022631-s4n24xij author: Jonsson, M. V. title: Germinal Centres in Primary Sjögren''s Syndrome Indicate a Certain Clinical Immunological Phenotype date: 2008-06-28 words: 16905.0 sentences: 873.0 pages: flesch: 46.0 cache: ./cache/cord-022631-s4n24xij.txt txt: ./txt/cord-022631-s4n24xij.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Ectopic germinal centers (GCs) can be detected in the salivary glands of approximately 1/5 of patients with Sjögren's syndrome (SS) and appear in both primary and secondary SS. Previously, ectopic GC have been associated with increased local autoantibody production. The aim of this study was to determine whether GC in primary Sjögren's syndrome (pSS) defines a distinct seroimmunological phenotype. Retrospectively, a material of 130 haematoxylin and eosin‐stained paraffin‐embedded tissue sections of minor salivary gland tissue from patients with pSS was morphologically screened for the presence of ectopic GC. GC‐like lesions were detected in 33/130 (25%) of the pSS patients. Seventy‐two pSS patients lacking these structures (GC‐) were randomly selected for comparison. Focus score was significantly increased in the GC(+) patients compared to the GC(–) patients (P = 0.035). In the GC(+) group, 54.5% of the patients presented with anti‐Ro/SSA compared to 43.7% in the GC(–) group. Anti‐La/SSB was detected in 31.3% of the GC(+) patients compared to 25.7% of the GC(–) patients. Sixty‐one percentage of GC(+) patients presented with increased levels of IgG, a nonsignificant difference when compared to 39.4% in the GC(–) patients (P = 0.089). Levels of RF, ANA, ENA, IgM and IgA were similar in both patient groups, as were ESR and CRP. In conclusion, patients with ectopic GC have a higher focus score and more often present with autoantibodies and increased levels of IgG compared to pSS patients with regular focal infiltration (GC(–)). Our findings may indicate a certain seroimmunological phenotype and warrant for further prospective studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159356/ doi: 10.1111/j.0300-9475.2004.01423h.x id: cord-304993-t4rua95e author: Jung, Kwonil title: The Effects of Simvastatin or Interferon-α on Infectivity of Human Norovirus Using a Gnotobiotic Pig Model for the Study of Antivirals date: 2012-07-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The lack of an animal model for human norovirus (HuNoV) has hindered the development of therapeutic strategies. This study demonstrated that a commonly used cholesterol-lowering statin medication, simvastatin, which increases HuNoV replication in an in vitro replicon system, also enhances HuNoV infectivity in the gnotobiotic (Gn) pig model. In contrast, oral treatment with interferon (IFN)-α reduces HuNoV infectivity. Young piglets, all with A or H1 histo-blood group antigens on enterocytes, were treated orally with 8 mg/kg/day of simvastatin; 5 days later, the pigs were inoculated orally with a GII.4 HuNoV (HS194/2009/US strain) and then treated with simvastatin for 5 more days. Simvastatin induced significantly earlier onset and longer duration of HuNoV fecal shedding in treated pigs, frequently with higher fecal viral titers. Simvastatin impaired poly (I:C)-induced IFN-α expression in macrophages or dendritic cells, possibly due to lowered toll-like receptor (TLR) 3 expression; however, the mechanisms were not related to interferon regulatory factor 3 or nuclear factor kappa B signaling pathway. Thus, the enhanced, earlier infectivity of HuNoV in simvastatin-treated pigs coincided with the inhibitory effect of simvastatin on innate immunity. In contrast to the increased HuNoV shedding that simvastatin induced, viral shedding during the treatment period was reduced or curtailed in the HuNoV-inoculated pigs pre-treated/treated with human IFN-α. Our findings are the first to indicate that IFN-α has potential as antiviral therapy against HuNoV. Based on these intriguing and novel findings using the Gn pig model, we confirmed that HuNoV infectivity is altered by treatment with simvastatin or IFN-α. Collectively, these findings indicate that Gn pigs are a useful model to test immunomodulators or efficacy of antivirals against HuNoV. url: https://www.ncbi.nlm.nih.gov/pubmed/22911825/ doi: 10.1371/journal.pone.0041619 id: cord-288017-f9b3t0ts author: Kabeerdoss, Jayakanthan title: Understanding immunopathological fallout of human coronavirus infections including COVID‐19: Will they cross the path of rheumatologists? date: 2020-08-10 words: 4281.0 sentences: 280.0 pages: flesch: 46.0 cache: ./cache/cord-288017-f9b3t0ts.txt txt: ./txt/cord-288017-f9b3t0ts.txt summary: High risks for fatal disease in COVID‐19 include older age, metabolic syndrome, male gender, and individuals who develop delayed type I IFN response. 54 In a macaque model of SARS-CoV infection too, aged macaques had more severe lung pathology, lower expression of type I IFN and higher expression of pro-inflammatory cytokines as compared to younger macaques. 80 to patients with COVID-19 that it is a mild immunomodulatory F I G U R E 2 Hydroxychloroquine (HCQ) inhibits SARS-CoV-2 entry and inhibits virus-induced type I interferon (IFN) signaling and proinflammatory cytokines production. While male gender, older age and people with metabolic syndrome seem to be at a higher risk of contracting more severe SARS-CoV-2 infection, younger females of African and Asian ancestry have higher risk for developing SLE; male gender among lupus patients, however, is an independent risk factor for severe disease. Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice abstract: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causing coronavirus disease 2019 (COVID‐19) is the biggest pandemic of our lifetime to date. No effective treatment is yet in sight for this catastrophic illness. Several antiviral agents and vaccines are in clinical trials, and drug repurposings as immediate and alternative choices are also under consideration. Immunomodulatory agents like hydroxychloroquine (HCQ) as well as biological disease‐modifying anti‐rheumatic drugs (bDMARDs) such as tocilizumab and anakinra received worldwide attention for treatment of critical patients with COVID‐19. This is of interest to rheumatologists, who are well versed with rational use of these agents. This brief review addresses the understandings of some of the common immunopathogenetic mechanisms in the context of autoimmune rheumatic diseases like systemic lupus erythematosus (SLE) and COVID‐19. Apart from demographic comparisons, the role of type I interferons (IFN), presence of antiphospholipid antibodies and finally mechanism of action of HCQ in both the scenarios are discussed here. High risks for fatal disease in COVID‐19 include older age, metabolic syndrome, male gender, and individuals who develop delayed type I IFN response. HCQ acts by different mechanisms including prevention of cellular entry of SARS‐CoV‐2 and inhibition of type I IFN signaling. Recent controversies regarding efficacy of HCQ in management of COVID‐19 warrant more studies in that direction. Autoantibodies were also reported in severe acute respiratory syndrome (SARS) as well as in COVID‐19. Rheumatologists need to wait and see whether SARS‐CoV‐2 infection triggers development of autoimmunity in patients with COVID‐19 infection in the long run. url: https://doi.org/10.1111/1756-185x.13909 doi: 10.1111/1756-185x.13909 id: cord-256293-5lpe8hg2 author: Kageyama, Y. title: Jinhua Qinggan granule, a Chinese herbal medicine against COVID-19, induces rapid changes in the plasma levels of IL-6 and IFN-γ date: 2020-06-12 words: 1815.0 sentences: 137.0 pages: flesch: 54.0 cache: ./cache/cord-256293-5lpe8hg2.txt txt: ./txt/cord-256293-5lpe8hg2.txt summary: title: Jinhua Qinggan granule, a Chinese herbal medicine against COVID-19, induces rapid changes in the plasma levels of IL-6 and IFN-γ However, in China, traditional Chinese herbal medicines have provided therapeutic benefit to patients with COVID-19. Jinhua Qinggan granule (JHQGG) is a Chinese multi-herbal formula previously developed for the treatment of H1N1 influenza and has been encouraged for patients clinically suspected of COVID-19 during medical observation. On the basis of its therapeutic efficacy for influenza, JHQGG has been recommended for patients clinically suspected of COVID-19 during medical observation. Notably, in blood cytokine analysis, the plasma levels of IL-6 and IFN-γ were significantly decreased and increased, respectively, compared with those in pre-administration (IL-6, 2.75 vs. The rapid immunomodulatory effects of JHQGG may be able to remedy the immune dysregulation observed in COVID-19 patients All rights reserved. Herbal medicine for the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of randomized controlled trials abstract: Background: Currently, effective vaccines or specific therapeutic agents against COVID-19 are not available. However, in China, traditional Chinese herbal medicines have provided therapeutic benefit to patients with COVID-19. Jinhua Qinggan granule (JHQGG) is a Chinese multi-herbal formula previously developed for the treatment of H1N1 influenza and has been encouraged for patients clinically suspected of COVID-19 during medical observation. However, the immunological mechanism for the efficacy of JHQGG has not been confirmed. Objectives: We thus examined whether the administration of JHQGG affects hematological and immunological measures in healthy individuals. Method: We enrolled 18 healthy volunteers, all of whom tested negative for antibodies to SARS-CoV-2. Peripheral blood samples were collected 1 h after oral administration of JHQGG and subjected to hematological, biochemical, and cytokine tests. Results: JHQGG rapidly induced a significant decrease in the plasma level of IL-6 and an increase in the plasma level of IFN-{gamma}. Conclusions: Our finding suggests that the therapeutic efficacy of JHQGG against COVID-19 is, in part, associated with its rapid immunomodulatory activity. url: http://medrxiv.org/cgi/content/short/2020.06.08.20124453v1?rss=1 doi: 10.1101/2020.06.08.20124453 id: cord-004334-y1fcw1dj author: Kalodimou, Georgia title: A Soluble Version of Nipah Virus Glycoprotein G Delivered by Vaccinia Virus MVA Activates Specific CD8 and CD4 T Cells in Mice date: 2019-12-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Nipah virus (NiV) is an emerging zoonotic virus that is transmitted by bats to humans and to pigs, causing severe respiratory disease and often fatal encephalitis. Antibodies directed against the NiV-glycoprotein (G) protein are known to play a major role in clearing NiV infection and in providing vaccine-induced protective immunity. More recently, T cells have been also shown to be involved in recovery from NiV infection. So far, relatively little is known about the role of T cell responses and the antigenic targets of NiV-G that are recognized by CD8 T cells. In this study, NiV-G protein served as the target immunogen to activate NiV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for the generation of MVA–NiV-G candidate vaccines expressing different versions of recombinant NiV-G. Overlapping peptides covering the entire NiV-G protein were used to identify major histocompatibility complex class I/II-restricted T cell responses in type I interferon receptor-deficient (IFNAR−/−) mice after vaccination with the MVA–NiV-G candidate vaccines. We have identified an H2-b-restricted nonamer peptide epitope with CD8 T cell antigenicity and a H2-b 15mer with CD4 T cell antigenicity in the NiV-G protein. The identification of this epitope and the availability of the MVA–NiV-G candidate vaccines will help to evaluate NiV-G-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of NiV-G infection. Of note, a soluble version of NiV-G was advantageous in activating NiV-G-specific cellular immune responses using these peptides. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019319/ doi: 10.3390/v12010026 id: cord-023415-hhvmsn5b author: Karlsson, H. title: Pattern of Cytokine Responses to Gram‐Positive and Gram‐Negative Commensal Bacteria is Profoundly Changed when Monocytes Differentiate into Dendritic Cells date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The normal gastrointestinal flora is crucial for the maturation of the acquired immunity via effects on antigen‐presenting cells (APCs). Here, we have investigated how two types of APCs, monocytes and dendritic cells (DCs), react to different bacterial strains typical of the commensal intestinal flora. Purified monocytes and monocyte‐derived DCs were stimulated with UV‐inactivated gram‐positive (Lactobacillus plantarum and Bifidobacterium adolescentis) and gram‐negative (Escherichia coli and Veillonella parvula) bacterial strains. Monocytes produced higher levels of IL‐12p70 and TNF, as detected by ELISA, in response to L. plantarum than to E. coli and V. parvula. In contrast, DCs secreted high amounts of IL‐12p70, TNF, IL‐6 and IL‐10 in response to E. coli and V. parvula but were practically unresponsive to L. plantarum and B. adolescentis. The lack of response to the gram‐positive strains correlated with a lower surface expression of Toll‐like reseptor 2 (TLR2) on DCs compared to monocytes. The surface expression of TLR4 on DCs was undetectable when analysed by flow cytometry, but blocking this receptor decreased the TNF production in response to V. parvula, indicating that low TLR4 expression on DCs is sufficient to mount an inflammatory response to gram‐negative bacteria. IFN‐γ increased the expression of TLR4 on DCs and also potentiated the cytokine response to gram‐negative bacteria. Our results indicate that, when monocytes differentiate into DCs, their ability to respond to different commensal bacteria dramatically changes, thereby becoming unresponsive to probiotic gram‐positive bacteria. These results may have important implications for the capacity of different groups of commensal bacteria to regulate mucosal and systemic immunity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169557/ doi: 10.1111/j.0300-9475.2004.01423at.x id: cord-278569-yr06jwm1 author: Karnam, Guruswamy title: CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection date: 2012-05-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200(−/−) mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R. url: https://doi.org/10.1371/journal.ppat.1002710 doi: 10.1371/journal.ppat.1002710 id: cord-311823-85wj08gr author: Katze, Michael G. title: Innate immune modulation by RNA viruses: emerging insights from functional genomics date: 2008 words: 9154.0 sentences: 392.0 pages: flesch: 36.0 cache: ./cache/cord-311823-85wj08gr.txt txt: ./txt/cord-311823-85wj08gr.txt summary: In this section, we review recent studies in which genomic approaches have been used to provide new information on how viruses trigger and regulate innate immune pathways, and to evaluate the use of type I IFN-based therapy as a means to enhance the innate immune response to HCV. In RIg-I-deficient cells, influenza virus fails to elicit the expression of IFNβ and of many ISgs, including key antiviral mediators such as IRF3, STAT1 (signal transducer and activator of transcription 1), IFIT1 (IFN-induced protein with tetratricopeptide repeats 1; also known as ISg56) and ISg54 (also known as IFIT2). Although these studies have provided considerable information regarding the genes activated downstream of TlR activation, it will be advantageous to extend genomic analyses in the context of viral infection using cells lacking the expression of specific TlRs. The ability of a virus to establish an infection depends, at least to some extent, on its ability to block the host innate immune response or to modulate the activity of antiviral effector proteins. abstract: Although often encoding fewer than a dozen genes, RNA viruses can overcome host antiviral responses and wreak havoc on the cells they infect. Some manage to evade host antiviral defences, whereas others elicit an aberrant or disproportional immune response. Both scenarios can result in the disruption of intracellular signalling pathways and significant pathology in the host. Systems-biology approaches are increasingly being used to study the processes of viral triggering and regulation of host immune responses. By providing a global and integrated view of cellular events, these approaches are beginning to unravel some of the complexities of virus–host interactions and provide new insights into how RNA viruses cause disease. url: https://doi.org/10.1038/nri2377 doi: 10.1038/nri2377 id: cord-000125-uvf5qzfd author: Kenworthy, Rachael title: Short-hairpin RNAs delivered by lentiviral vector transduction trigger RIG-I-mediated IFN activation date: 2009-09-03 words: 6633.0 sentences: 336.0 pages: flesch: 54.0 cache: ./cache/cord-000125-uvf5qzfd.txt txt: ./txt/cord-000125-uvf5qzfd.txt summary: The interaction between a PAMP and a PRR triggers activation of the interferon (IFN) pathway in mammalian cells, which significantly changes the gene-expression profile in the cells and contributes to the well-documented off-target effect of RNAi. IFN induction is especially problematic in antiviral studies employing RNAi, where the antiviral effect of IFN must be distinguished from that of RNAi. Typical IFN-inducing structure patterns include dsRNA of certain length, single-stranded RNA (ssRNA) containing 5 0 -triphosphates (5 0 -ppp), the dsRNA analogue polyinosinic-polycytidylic acid (poly I:C), and certain dsDNA molecules. Mammalian expression plasmids encoding each of these proteins, as well as the dominant negative (DN) mutants of RIG-I and MDA5, were transfected into 293FT cells with shRNAs and an IFN-b promoter reporter construct. abstract: Activation of the type I interferon (IFN) pathway by small interfering RNA (siRNA) is a major contributor to the off-target effects of RNA interference in mammalian cells. While IFN induction complicates gene function studies, immunostimulation by siRNAs may be beneficial in certain therapeutic settings. Various forms of siRNA, meeting different compositional and structural requirements, have been reported to trigger IFN activation. The consensus is that intracellularly expressed short-hairpin RNAs (shRNAs) are less prone to IFN activation because they are not detected by the cell-surface receptors. In particular, lentiviral vector-mediated transduction of shRNAs has been reported to avoid IFN response. Here we identify a shRNA that potently activates the IFN pathway in human cells in a sequence- and 5′-triphosphate-dependent manner. In addition to suppressing its intended mRNA target, expression of the shRNA results in dimerization of interferon regulatory factor-3, activation of IFN promoters and secretion of biologically active IFNs into the extracellular medium. Delivery by lentiviral vector transduction did not avoid IFN activation by this and another, unrelated shRNA. We also demonstrated that retinoic-acid-inducible gene I, and not melanoma differentiation associated gene 5 or toll-like receptor 3, is the cytoplasmic sensor for intracellularly expressed shRNAs that trigger IFN activation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770676/ doi: 10.1093/nar/gkp714 id: cord-288238-36hiiw91 author: Keshavarz, Mohsen title: Metabolic host response and therapeutic approaches to influenza infection date: 2020-03-05 words: 8134.0 sentences: 425.0 pages: flesch: 32.0 cache: ./cache/cord-288238-36hiiw91.txt txt: ./txt/cord-288238-36hiiw91.txt summary: It is also reported that influenza infection significantly increases ROS production by inducing Nox4, and the proliferation of this virus in lung epithelial cells is dependent on redox-sensitive pathways activated by Nox4-derived ROS [16] . IFN can also exert its function on metabolic changes by producing several mediators including indoleamine-2,3-dioxygenase (IDO) and nitric oxide (NO), both of which appear to have either an inducible or an inhibitory role in viral replication [33] . In addition, increased temperature of cells during infection (which could be the result of virus replication and fever) causes heat stress which in turn can considerably downregulate carnitine palmitoyltransferase II (CPT II) activity and reduce the β-oxidation and ATP levels in fibroblasts of influenza-associated encephalopathy patients and healthy volunteers [110] . Through enhancing the activity of the mTORC1 complex, the influenza virus strengthens several metabolic pathways, including glycolysis, glutaminolysis, pentose phosphate, and fatty acid synthesis, to provide more ATP and structural materials for viral replication. abstract: Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid β-oxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways. url: https://www.ncbi.nlm.nih.gov/pubmed/32161622/ doi: 10.1186/s11658-020-00211-2 id: cord-253862-jl1zhg13 author: Khalaf, Khalil title: SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date: 2020-10-06 words: 14595.0 sentences: 760.0 pages: flesch: 45.0 cache: ./cache/cord-253862-jl1zhg13.txt txt: ./txt/cord-253862-jl1zhg13.txt summary: Although this novel virus is less severe than the first SARS-CoV outbreak, human-to-human transmission remains very high and the number of cases continues to rise exponentially in major urban areas, highlighting the urgent need to develop new containment, diagnostic, and treatment protocols. In the case of SARS-CoV-2, viral evasion of the innate immune system leads to an increase in cytokine production and late CD4+/CD8+ response, which then leads to pathogenic inflammation in patients with high viral loads. (ChiCTR2000029308), involving severe SARS-CoV-2 cases, compared lopinavir/ritonavir treatment with standard care alone, and they showed that the antivirals yielded no clinical benefits. In an open-label control study conducted by Cai et al., the antiviral activity of favipiravir + IFN-α was compared to that of lopinavir/ritonavir + IFN-α in patients with confirmed SARS-CoV-2 infection. abstract: The emergence and rapid spread of SARS-CoV-2 in December 2019 has brought the world to a standstill. While less pathogenic than the 2002–2003 SARS-CoV, this novel betacoronavirus presents a global threat due to its high transmission rate, ability to invade multiple tissues, and ability to trigger immunological hyperactivation. The identification of the animal reservoir and intermediate host were important steps toward slowing the spread of disease, and its genetic similarity to SARS-CoV has helped to determine pathogenesis and direct treatment strategies. The exponential increase in cases has necessitated fast and reliable testing procedures. Although RT-PCR remains the gold standard, it is a time-consuming procedure, paving the way for newer techniques such as serologic tests and enzyme immunoassays. Various clinical trials using broad antiviral agents in addition to novel medications have produced controversial results; however, the advancement of immunotherapy, particularly monoclonal antibodies and immune modulators is showing great promise in clinical trials. Non-orthodox medications such as anti-malarials have been tested in multiple institutions but definitive conclusions are yet to be made. Adjuvant therapies have also proven to be effective in decreasing mortality in the disease course. While no formal guidelines have been established, the multitude of ongoing clinical trials as a result of unprecedented access to research data brings us closer to halting the SARS-CoV-2 pandemic. url: https://doi.org/10.3389/fimmu.2020.570927 doi: 10.3389/fimmu.2020.570927 id: cord-328252-dk54w8z9 author: Kikkert, Marjolein title: Innate Immune Evasion by Human Respiratory RNA Viruses date: 2019-10-14 words: 11552.0 sentences: 550.0 pages: flesch: 43.0 cache: ./cache/cord-328252-dk54w8z9.txt txt: ./txt/cord-328252-dk54w8z9.txt summary: Whether PA-X also degrades viral dsRNA species to prevent recognition by cytosolic RNA sensors is not entirely clear, but mutant viruses in which this PA-X protein was expressed in significantly lower amounts elicited higher levels of innate immune response; for example, IFN-beta production was much higher in these infections [71] . This indeed suggests that PA-X, besides having a role in the degradation of cellular mRNAs, may also degrade viral RNA to prevent recognition by innate immune sensors and activation of innate immune responses, similar to what was shown for the CoVs. To my knowledge, an endoribonuclease has not been identified in the RSV genome, so this virus may use alternative innate immune evasion strategies, as discussed elsewhere in this review. [91] suggested that RSV specifically targets mRNA encoding surfactant protein A, an innate immune factor with an important role in the epithelial tissue of the lung, which directly binds to virus particles to cause their destruction by host defense mechanisms. abstract: The impact of respiratory virus infections on the health of children and adults can be very significant. Yet, in contrast to most other childhood infections as well as other viral and bacterial diseases, prophylactic vaccines or effective antiviral treatments against viral respiratory infections are either still not available, or provide only limited protection. Given the widespread prevalence, a general lack of natural sterilizing immunity, and/or high morbidity and lethality rates of diseases caused by influenza, respiratory syncytial virus, coronaviruses, and rhinoviruses, this difficult situation is a genuine societal challenge. A thorough understanding of the virus-host interactions during these respiratory infections will most probably be pivotal to ultimately meet these challenges. This review attempts to provide a comparative overview of the knowledge about an important part of the interaction between respiratory viruses and their host: the arms race between host innate immunity and viral innate immune evasion. Many, if not all, viruses, including the respiratory viruses listed above, suppress innate immune responses to gain a window of opportunity for efficient virus replication and setting-up of the infection. The consequences for the host's immune response are that it is often incomplete, delayed or diminished, or displays overly strong induction (after the delay) that may cause tissue damage. The affected innate immune response also impacts subsequent adaptive responses, and therefore viral innate immune evasion often undermines fully protective immunity. In this review, innate immune responses relevant for respiratory viruses with an RNA genome will briefly be summarized, and viral innate immune evasion based on shielding viral RNA species away from cellular innate immune sensors will be discussed from different angles. Subsequently, viral enzymatic activities that suppress innate immune responses will be discussed, including activities causing host shut-off and manipulation of stress granule formation. Furthermore, viral protease-mediated immune evasion and viral manipulation of the ubiquitin system will be addressed. Finally, perspectives for use of the reviewed knowledge for the development of novel antiviral strategies will be sketched. url: https://doi.org/10.1159/000503030 doi: 10.1159/000503030 id: cord-002021-67ao8chx author: Kim, Seong Bum title: Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses date: 2016-04-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Japanese encephalitis (JE), a leading cause of viral encephalitis, is characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV). Indoleamine 2,3-dioxygenase (IDO) has been identified as an enzyme associated with immunoregulatory function. Although the regulatory role of IDO in viral replication has been postulated, the in vivo role of IDO activity has not been fully addressed in neurotropic virus-caused encephalitis. METHODS: Mice in which IDO activity was inhibited by genetic ablation or using a specific inhibitor were examined for mortality and clinical signs after infection. Neuroinflammation was evaluated by central nervous system (CNS) infiltration of leukocytes and cytokine expression. IDO expression, viral burden, JEV-specific T-cell, and type I/II interferon (IFN-I/II) innate responses were also analyzed. RESULTS: Elevated expression of IDO activity in myeloid and neuron cells of the lymphoid and CNS tissues was closely associated with clinical signs of JE. Furthermore, inhibition of IDO activity enhanced resistance to JE, reduced the viral burden in lymphoid and CNS tissues, and resulted in early and increased CNS infiltration by Ly-6C(hi) monocytes, NK, CD4(+), and CD8(+) T-cells. JE amelioration in IDO-ablated mice was also associated with enhanced NK and JEV-specific T-cell responses. More interestingly, IDO ablation induced rapid enhancement of type I IFN (IFN-I) innate responses in CD11c(+) dendritic cells (DCs), including conventional and plasmacytoid DCs, following JEV infection. This enhanced IFN-I innate response in IDO-ablated CD11c(+) DCs was coupled with strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7, STAT1), and antiviral ISG genes (Mx1, Mx2, ISG49, ISG54, ISG56). IDO ablation also enhanced the IFN-I innate response in neuron cells, which may delay the spread of virus in the CNS. Finally, we identified that IDO ablation in myeloid cells derived from hematopoietic stem cells (HSCs) dominantly contributed to JE amelioration and that HSC-derived leukocytes played a key role in the enhanced IFN-I innate responses in the IDO-ablated environment. CONCLUSIONS: Inhibition of IDO activity ameliorated JE via enhancement of antiviral IFN-I/II innate and adaptive T-cell responses and increased CNS infiltration of peripheral leukocytes. Therefore, our data provide valuable insight into the use of IDO inhibition by specific inhibitors as a promising tool for therapeutic and prophylactic strategies against viral encephalitis caused by neurotropic viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835894/ doi: 10.1186/s12974-016-0551-5 id: cord-290744-m0vpizuh author: Kindler, E. title: Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response date: 2016-09-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are the most severe coronavirus (CoV)-associated diseases in humans. The causative agents, SARS-CoV and MERS-CoV, are of zoonotic origin but may be transmitted to humans, causing severe and often fatal respiratory disease in their new host. The two coronaviruses are thought to encode an unusually large number of factors that allow them to thrive and replicate in the presence of efficient host defense mechanisms, especially the antiviral interferon system. Here, we review the recent progress in our understanding of the strategies that highly pathogenic coronaviruses employ to escape, dampen, or block the antiviral interferon response in human cells. url: https://api.elsevier.com/content/article/pii/S0065352716300458 doi: 10.1016/bs.aivir.2016.08.006 id: cord-343221-e29of29o author: Kindler, Eveline title: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication date: 2017-02-03 words: 7896.0 sentences: 423.0 pages: flesch: 51.0 cache: ./cache/cord-343221-e29of29o.txt txt: ./txt/cord-343221-e29of29o.txt summary: Specifically, we show that genetically engineered mutants of mouse hepatitis virus (MHV) and human coronavirus 229E (HCoV-229E), respectively, that encode an EndoU active-site substitution known to abolish nucleolytic activity, were severely attenuated and elicited an immediate and simultaneous activation of host cell dsRNA sensors. The severe attenuation of MHV H277A and HCoV-229E H250A replication in wild-type murine and human macrophages, respectively, precluded the use of primary macrophages to assess the sensitivity of EndoU-deficient coronaviruses to IFN-I pre-treatment. Our data suggest that direct restriction of replication of EndoU-deficient coronaviruses is mediated by RNase L-mediated RNA degradation and inhibition of host cell translation through activation of PKR. Notably, also in this case Xrn1 is required to further process the de-capped mRNAs. Our data show that early during coronavirus infection the EndoU activity conceptually fulfils the same task, namely the removal of dsRNA that would otherwise trigger host cell dsRNA responses, such as IFN-β expression and activation of PKR and OAS/RNase L. abstract: Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. In macrophages we found immediate induction of IFN-I expression and RNase L-mediated breakdown of ribosomal RNA. Accordingly, EndoU-deficient viruses can retain replication only in cells that are deficient in IFN-I expression or sensing, and in cells lacking both RNase L and PKR. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. The localization of the EndoU activity at the site of viral RNA synthesis–within the replicase complex—suggests that coronaviruses have evolved a viral RNA decay pathway to evade early innate and intrinsic antiviral host cell responses. url: https://www.ncbi.nlm.nih.gov/pubmed/28158275/ doi: 10.1371/journal.ppat.1006195 id: cord-003614-63rzzos3 author: Klotz, Daniela title: Interferon-Stimulated Genes—Mediators of the Innate Immune Response during Canine Distemper Virus Infection date: 2019-04-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The demyelinating canine distemper virus (CDV)-leukoencephalitis represents a translational animal model for multiple sclerosis. The present study investigated the expression of type I interferon (IFN-I) pathway members in CDV-induced cerebellar lesions to gain an insight into their role in lesion development. Gene expression of 110 manually selected genes in acute, subacute and chronic lesions was analyzed using pre-existing microarray data. Interferon regulatory factor (IRF) 3, IRF7, signal transducer and activator of transcription (STAT) 1, STAT2, MX protein, protein kinase R (PKR), 2′-5′-oligoadenylate synthetase (OAS) 1 and interferon-stimulated gene (ISG) 15 expression were also evaluated using immunohistochemistry. Cellular origin of STAT1, STAT2, MX and PKR were determined using immunofluorescence. CDV infection caused an increased expression of the antiviral effector proteins MX, PKR, OAS1 and ISG15, which probably contributed to a restricted viral replication, particularly in neurons and oligodendrocytes. This increase might be partly mediated by IRF-dependent pathways due to the lack of changes in IFN-I levels and absence of STAT2 in astrocytes. Nevertheless, activated microglia/macrophages showed a strong expression of STAT1, STAT2 and MX proteins in later stages of the disease, indicating a strong activation of the IFN-I signaling cascade, which might be involved in the aggravation of bystander demyelination. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480560/ doi: 10.3390/ijms20071620 id: cord-023410-eblcf902 author: Kollgaard, T. M. title: Clonally Expanded CD8(+) T cells in Allogeneic Bone Marrow Transplantation date: 2008-06-28 words: 16915.0 sentences: 872.0 pages: flesch: 46.0 cache: ./cache/cord-023410-eblcf902.txt txt: ./txt/cord-023410-eblcf902.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Allogeneic bone marrow transplantation (BMT) is a potentially curative therapy for patients with haematologic malignancies. Several lines of evidence demonstrate that donor T cells are involved in the antitumour effects observed after BMT. Thus, patients receiving T‐cell‐depleted BMT have a higher risk of leukaemia relapse compared to patients receiving nonmanipulated BMT, and patients experiencing graft‐versus‐host disease (GVHD) have a lower risk of disease relapse than patients who do not experience GVHD. Although the importance of donor T cells for the curative action of BMT has been established, the exact mechanisms and molecules involved in this graft‐versus‐tumour effect remain largely unknown. In a recently initiated project, we have conducted a longitudinal study of T‐cell clonotypes in patients who received peripheral blood stem cell grafts after nonmyeloablative conditioning. Peripheral blood samples were obtained sequentially after transplant, and the mononuclear cells (MNCs) were isolated and cryopreserved. CD8(+) T cells were isolated from the MNCs by use of immunomagnetic beads or FACS and analysed for the presence of clonally expanded cells by T‐cell receptor clonotype mapping based on RT‐PCR and denaturing gradient gel electrophoresis (DGGE). Using this gel‐based methodology, clonally expanded T cells were monitored after transplant and compared to the clinical data of the patients. The preliminary results demonstrates the presence of clonally expanded CD8(+) T cells at all time points analysed. Furthermore, a number of clonotypes persisted for more than 6 months, and other clonotypes emerged during this period. The appearance of newly emerged clonotypes which coincided with clinical GVHD could indicate a role for these T cells in the pathogenesis of GVHD. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169548/ doi: 10.1111/j.0300-9475.2004.01423bm.x id: cord-305093-og4k3fc7 author: Konno, Yoriyuki title: SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is increased by a naturally occurring elongation variant date: 2020-09-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays reveal that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of approximately 17,000 SARS-CoV-2 sequences identify a natural variant, in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients, but also describe the emergence of natural SARS-CoV-2 quasispecies with an extended ORF3b gene that may potentially affect COVID-19 pathogenesis. url: https://api.elsevier.com/content/article/pii/S2211124720311748 doi: 10.1016/j.celrep.2020.108185 id: cord-287018-g4y5kjju author: Konstantinova, P title: Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA date: 2006-05-18 words: 7164.0 sentences: 454.0 pages: flesch: 56.0 cache: ./cache/cord-287018-g4y5kjju.txt txt: ./txt/cord-287018-g4y5kjju.txt summary: In order to solve this durability problem, we tested DNA constructs encoding virus-specific long-hairpin RNAs (lhRNAs) for their ability to inhibit HIV-1 production. The lhRNA constructs were compared with in vitro diced double-stranded RNA and a DNA construct encoding an effective nef-specific shRNA for their ability to inhibit HIV-1 production in cells. For this reason, the DNA constructs encoding lhRNAs (a single-hairpin molecule) and long dsRNAs (two complementary molecules that form a duplex) were designed to target tat, rev and nef sequences as indicated in Figure 1 . 21 nef2 dsRNA induced a decrease in luciferase expression, but an even more pronounced level of inhibition was Figure 1 Scheme of the human immunodeficiency virus type 1 (HIV-1) pLAI proviral genome and target sequences used for the design of long-hairpin RNAs (lhRNAs). abstract: Inhibition of virus replication by means of RNA interference has been reported for several important human pathogens, including human immunodeficiency virus type 1 (HIV-1). RNA interference against these pathogens has been accomplished by introduction of virus-specific synthetic small interfering RNAs (siRNAs) or DNA constructs encoding short-hairpin RNAs (shRNAs). Their use as therapeutic antiviral against HIV-1 is limited, because of the emergence of viral escape mutants. In order to solve this durability problem, we tested DNA constructs encoding virus-specific long-hairpin RNAs (lhRNAs) for their ability to inhibit HIV-1 production. Expression of lhRNAs in mammalian cells may result in the synthesis of many siRNAs targeting different viral sequences, thus providing more potent inhibition and reducing the chance of viral escape. The lhRNA constructs were compared with in vitro diced double-stranded RNA and a DNA construct encoding an effective nef-specific shRNA for their ability to inhibit HIV-1 production in cells. Our results show that DNA constructs encoding virus-specific lhRNAs are capable of inhibiting HIV-1 production in a sequence-specific manner, without inducing the class I interferon genes. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/sj.gt.3302786) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/16708080/ doi: 10.1038/sj.gt.3302786 id: cord-310861-9kb0b6rq author: Koo, Bonhan title: An isothermal, label-free, and rapid one-step RNA amplification/detection assay for diagnosis of respiratory viral infections date: 2017-04-15 words: 5584.0 sentences: 295.0 pages: flesch: 58.0 cache: ./cache/cord-310861-9kb0b6rq.txt txt: ./txt/cord-310861-9kb0b6rq.txt summary: In this study, we report an isothermal and rapid one-step RNA amplification/detection (iROAD) assay to simultaneously amplify and detect the viral RNA in a label-free and real-time manner. Furthermore, we demonstrated the clinical utility of the iROAD assay by detecting respiratory viral RNAs extracted from the 63 nasopharyngeal samples with either IFN-A/B or HCoV-OC43/229E or RSV-A/B. Subsequently, the iROAD assay detected the respiratory viral targets from the clinical sample by measuring the resonance wavelength shift within 15-20 min (Fig. 1) . In case of the iROAD assay with label-free and real-time capabilities, the wavelength shift was sequentially increased based on the concentrations (2.5×10 1 to 10 5 copies/reaction) of IFN-B within 20 min, as compared to the negative control. In the case of the real-time RT-PCR assay, the fluorescent SYBR Green signal was observed in RNA samples diluted up to 2.5×10 2 copies/reaction and showed good linearity (R 2 =0.9795) for different concentrations of the target (Fig. 3C ). abstract: Recently, RNA viral infections caused by respiratory viruses, such as influenza, parainfluenza, respiratory syncytial virus, coronavirus, and Middle East respiratory syndrome-coronavirus (MERS-CoV), and Zika virus, are a major public health threats in the world. Although myriads of diagnostic methods based on RNA amplification have been developed in the last decades, they continue to lack speed, sensitivity, and specificity for clinical use. A rapid and accurate diagnostic method is needed for appropriate control, including isolation and treatment of the patients. Here, we report an isothermal, label-free, one-step RNA amplification and detection system, termed as iROAD, for the diagnosis of respiratory diseases. It couples a one-step isothermal RNA amplification method and a bio-optical sensor for simultaneous viral RNA amplification/detection in a label-free and real-time manner. The iROAD assay offers a one-step viral RNA amplification/detection example to rapid analysis (<20 min). The detection limit of iROAD assay was found to be 10-times more sensitive than that of real-time reverse transcription-PCR method. We confirmed the clinical utility of the iROAD assay by detecting viral RNAs obtained from 63 human respiratory samples. We envision that the iROAD assay will be useful and potentially adaptable for better diagnosis of emerging infectious diseases including respiratory diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/27894035/ doi: 10.1016/j.bios.2016.11.051 id: cord-001515-x11t9pbv author: Kosinska, Anna D. title: Therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis B: preclinical studies in the woodchuck date: 2014-12-23 words: 6390.0 sentences: 312.0 pages: flesch: 37.0 cache: ./cache/cord-001515-x11t9pbv.txt txt: ./txt/cord-001515-x11t9pbv.txt summary: Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. The results of these studies clearly showed that combination of antiviral treatment and vaccination is more effective in inducing virus-specific T cell responses than therapeutic vaccination alone. The DNA prime-AdV boost immunization strategy was further used as a therapeutic vaccine against chronic WHV infection in combination with antiviral treatment with ETV. T-helper cell response to woodchuck hepatitis virus antigens after therapeutic vaccination of chronically-infected animals treated with lamivudine abstract: Infection with hepatitis B virus (HBV) may lead to subclinical, acute or chronic hepatitis. In the prevaccination era, HBV infections were endemic due to frequent mother to child transmission in large regions of the world. However, there are still estimated 240 million chronic HBV carriers today and ca. 620,000 patients die per year due to HBV-related liver diseases. Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory results. Induction of HBV-specific T cells by therapeutic vaccination or immunomodulation may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients with or without therapeutic reduction of viral load did not result in effective immune control of HBV infection, suggesting that combination of antiviral treatment with new formulations of therapeutic vaccines is needed. The woodchuck (Marmota monax) and its HBV-like woodchuck hepatitis virus are a useful preclinical animal model for developing new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments using nucleos(t)ide analogues, with prime-boost vaccination using DNA vaccines, new hepadnaviral antigens or recombinant adenoviral vectors were tested in the woodchuck model. In this review, we summarize these encouraging results obtained with these therapeutic vaccines. In addition, we present potential innovations in immunostimulatory strategies by blocking the interaction of the inhibitory programmed death receptor 1 with its ligand in this animal model. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305085/ doi: 10.1007/s00430-014-0379-5 id: cord-023393-8nye3nc8 author: Krarup, A. title: Mannan‐Binding Lectin, L‐Ficolin and H‐Ficolin Selectively Binds to Different Bacteria date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Mannan‐binding lectin (MBL), L‐ficolin and H‐ficolin are pattern recognition molecules of the innate immune system. We investigated the ability of these molecules to bind to different serotypes and noncapsulated variants of Streptococcus pneumonia and Staphylococcus aureus. We found that MBL binds to noncapsulated S. aureus strain (Wood) but not any of the examined S. pneumoniae serotypes. L‐ficolin binds to some capsulated S. pneumoniae serotypes (11A, 11D and 11F) as well as some capsulated S. aureus serotypes (Type‐1, ‐8, ‐9, ‐11 and ‐12). H‐ficolin does not bind to any of the examined S. pneumoniae and S. aureus serotypes included in this study but did bind to a strain of Aerococcus viridans. When bound to bacteria, MBL and H‐ficolin initiated activation of complement factor C4, whereas L‐ficolin did not. During this study, quantitative assays for the three proteins were developed and the concentration in 97 plasma samples were determined and the median values were estimated at 0.8 μg of MBL/ml, 3.3 μg of L‐ficolin/ml and 18.4 μg of H‐ficolin/ml, respectively. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169518/ doi: 10.1111/j.0300-9475.2004.01423al.x id: cord-020717-niiib47f author: Kristensson, Krister title: Neuronal targeting and functional effects of infectious agents transmitted from animals to man date: 2003 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The nervous system is an «immune-privileged» site and can provide a reservoir to harbor as persistent or latent infections certain microbes that find their way to the brain. From an evolutionary standpoint, such infections are characterized at most times by low levels of the infectious agent in the systemic domain, except when multiplication has just taken place. Hence the ability for transmission of the pathogens from animals to Man will be determined by the availability of microbes to be transferred by a vector (e.g. in trypanosomiasis), or the amount of infective forms of the microbes shed into an environment (e.g. in toxoplasmosis). Using African trypanosomes, toxoplasma,Listeria and influenza A virus as examples, mechanisms by which microbes can spread and be targeted to and within the brain to cause various types of nervous system dysfunctions is reviewed. Newly revealed potentials of certain cytokines to stimulate neurons to control the growth, and even kill, microbes in their cell bodies is also described. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146993/ doi: 10.1007/bf02904487 id: cord-023438-g0k0vvdc author: Krog, J. title: The Effects of Hyperbaric Exposure on Human Peripheral Blood Mononuclear Cells, with Special Emphasis on Natural Killer Cell Cytotoxicity and Subsets date: 2008-06-28 words: 16880.0 sentences: 871.0 pages: flesch: 46.0 cache: ./cache/cord-023438-g0k0vvdc.txt txt: ./txt/cord-023438-g0k0vvdc.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Materials and methods: As an experimental physiological stress model, we examined the effects of hyperbaric exposure on peripheral blood mononuclear cells (PBMCs) obtained from venous blood drawn from eight divers during a simulated heliox saturation dive. Eight persons working in normobar atmosphere outside the pressurized chamber served as control donors. The spontaneous cytotoxicity of the PBMCs was estimated in a 4 h 51Cr‐release assay using k562 as NK‐sensitive target cells. The PBMCs were characterized, using 4‐colour flow cytometry, with special emphasis on the NK‐cell subsets. The data were statistically analysed using a multivariate regression model (Stata 8.2). P values <0.05 was considered statistically significant. Results: The estimated cytotoxicity increased significantly in both the group of divers and control donors during the dive (pdivers < 0.01 and pcontrols < 0.01). Although the cytotoxicity increased relatively more (P < 0.01) in the group of divers compared to the group of control donors between day 1 and 2. Discussion: The increased cytotoxicity of PBMC estimated in the group of divers indicate that parts of the cellular immune system are affected during the extreme physiological conditions induced during the initial phase of the presented experimental hyperbaric setup. The increase in cytotoxicity observed in the group of control donors could hypothetically reflect the stress level in persons working outside the pressurized chamber during the dive. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169595/ doi: 10.1111/j.0300-9475.2004.01423aa.x id: cord-341822-uk6kvxyd author: Kucherenko, A. M. title: IFNL4 polymorphism as a predictor of chronic hepatitis C treatment efficiency in Ukrainian patients date: 2016-10-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The aim of this study was to examine association between IFNL4 gene ss469415590 and treatment efficiency in group of Ukrainian PEG-interferon/ribavirin-treated chronic hepatitis C patients. Study group consisted of 92 unrelated hepatitis C virus genotype 1 mono-infected patients: case group–29 patients with late or absent virological response; control group–63 patients with sustained virological response. Study material was genomic DNA. Genotyping was performed using amplification-refractory mutation system PCR. Statistical analysis was performed using GenePop and OpenEpi statistical packages. Obtained results show that ss469415590 ΔG/ΔG genotype is associated with poor virological response (OR = 3.62; CI 95%: 1.12–11.67) in PEG-interferon/ribavirin-treated chronic hepatitis C patients from Ukraine. url: https://doi.org/10.3103/s0095452716050066 doi: 10.3103/s0095452716050066 id: cord-312386-88uwlmjx author: Kuchipudi, Suresh V. title: The Complex Role of STAT3 in Viral Infections date: 2015-06-25 words: 4633.0 sentences: 261.0 pages: flesch: 39.0 cache: ./cache/cord-312386-88uwlmjx.txt txt: ./txt/cord-312386-88uwlmjx.txt summary: Signal transducer and activators of transcription-3 (STAT3) regulates diverse biological functions including cell growth, differentiation, and apoptosis. Signal transducers and activators of transcription (STATs) are a family of transcription factors that play crucial roles in regulating a number of diverse biological functions including cell proliferation, differentiation, apoptosis, inflammatory response, immunity, and angiogenesis [1] . The seemingly contradictory roles of STAT3 in viral infections raise a number of interesting questions: "what factors determine the switch between pro-and anti-inflammatory functions of STAT3?," "how are viruses able to exploit STAT3 signalling for their gene replication?," and "does STAT3 either negatively or positively regulate type 1 IFN response depending on the virus type involved?" Further in depth studies to dissect the role of STAT3 in viral infections could provide valuable insights into viral pathogenesis and development of novel antiviral therapies. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins abstract: Signal transducer and activators of transcription-3 (STAT3) regulates diverse biological functions including cell growth, differentiation, and apoptosis. In addition, STAT3 plays a key role in regulating host immune and inflammatory responses and in the pathogenesis of many cancers. Several studies reported differential regulation of STAT3 in a range of viral infections. Interestingly, STAT3 appears to direct seemingly contradictory responses and both pro- and antiviral roles of STAT3 have been described. This review summarized the currently known functions of STAT3 in the regulation of viral replication and pathogenesis of viral infections. Some of the key unanswered questions and the gap in our current understanding of the role of STAT3 in viral pathogenesis are discussed. url: https://doi.org/10.1155/2015/272359 doi: 10.1155/2015/272359 id: cord-327855-txryqil7 author: Kulka, M. title: The cytopathic 18f strain of Hepatitis A virus induces RNA degradation in FrhK4 cells date: 2003 words: 8706.0 sentences: 394.0 pages: flesch: 50.0 cache: ./cache/cord-327855-txryqil7.txt txt: ./txt/cord-327855-txryqil7.txt summary: Analysis of total cellular RNA from HM175/18f infected FrhK4 cells by denaturing agarose gel electrophoresis and Northern blot hybridization revealed extensive degradation of both the 28S and 18S ribosomal RNA (rRNA) molecules. In this study, we report that infection of FrhK4 cells with the HAV cp strain HM175/18f results in the degradation of ribosomal RNA (rRNA) and the reduction of several cellular mRNAs including β-actin and GAPDH. Degradation of rRNA is a feature of virus infection in interferon (IFN) treated cells and is believed to be due to the availability of double stranded RNA (dsRNA) during replication or transcription of the viral genome, resulting in the activation of the RNase L pathway [58, 59] . While the role of a viral protein in the activation of 2-5A/RNase L pathway in 18f or CBV1 infected FrhK4 cells cannot be ruled out, previous reports with EMC virus and the studies involving dsRNA clearly suggests a similar mechanism of rRNA degradation reported here. abstract: The mechanism responsible for the induction of apoptosis by the rapidly replicating HM175/18f strain of Hepatitis A virus (HAV) was investigated. Full length HAV RNA and viral capsid protein VP1 were detected in 18f infected cells at earlier times post-infection than in HM175/clone 1 infected cells. Analysis of total cellular RNA from HM175/18f infected FrhK4 cells by denaturing agarose gel electrophoresis and Northern blot hybridization revealed extensive degradation of both the 28S and 18S ribosomal RNA (rRNA) molecules. Similar degradation was observed when these cells were infected with Human coxsackievirus B1, a fast replicating enterovirus. In contrast, the parental strain of 18f, HM175/clone 1 did not induce RNA degradation. Inhibition of RNA degradation correlated with inhibition of virus replication. The pattern of rRNA degradation resembled degradation of rRNAs by RNase L, an enzyme activated in interferon-treated cells following infection with certain viruses. Ribosomal RNA degradation was accompanied by the reduction in the levels of several cellular RNAs including those for β-actin and glyceraldehyde-3-phosphate dehydrogenase, while the levels of c-myc and c-jun were higher. Interferon mRNAs could not be detected in either infected or mock-infected control cells, and STAT1, a key regulator of interferon action was not phosphorylated following virus infection. These results reveal a heretofore-undescribed pathway that involves the regulation of RNA degradation and apoptosis following HAV/18f replication in FrhK4 cells. url: https://www.ncbi.nlm.nih.gov/pubmed/12827461/ doi: 10.1007/s00705-003-0110-0 id: cord-290396-cy4y8vnt author: Kumar, Matam Vijay title: Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells date: 2004-07-01 words: 5490.0 sentences: 363.0 pages: flesch: 61.0 cache: ./cache/cord-290396-cy4y8vnt.txt txt: ./txt/cord-290396-cy4y8vnt.txt summary: title: Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells We evaluated the expression and function of TLRs in human retinal pigment epithelial (RPE) cells. The presence of TLRs on RPE cells and the resultant TLR signaling in RPE cells suggest that these molecules may play an important role in innate and adaptive immune responses within the retina. Our data suggest that the binding of poly I:C, an analog of dsRNA, to TLR 3 on human RPE cells resulted in the production of IFN-h and other cytokines, chemokines, and adhesion molecules. Total RNA prepared from confluent monolayers of human RPE cells and from suspension cultures of U937 was used to evaluate the constitutive expression of TLR mRNA. To study the effects of TLR activators, human RPE cells were washed with serum-free media (SFM) and incubated in SFM for 12 h in the presence of poly I:C (100 Ag/ml ), LPS (5 Ag/ml), or IFN-g (100 U/ml). abstract: Toll-like receptors (TLRs) are crucial components of innate immunity that participate in host defense against microbial pathogens. We evaluated the expression and function of TLRs in human retinal pigment epithelial (RPE) cells. Real time PCR analysis revealed gene expression for TLRs 1–7, 9, and 10 in RPE cells. TLRs 1 and 3 were the most highly expressed TLRs. Protein expression for TLRs 2, 3, and 4 was observed on RPE cells and this expression was augmented by treatment with poly I:C or interferon-γ (IFN-γ). TLR 3 is the receptor for dsRNA, an intermediate of virus replication. Because RPE cells express TLR 3 and are frequently the site of virus replication within the retina, we evaluated TLR 3 signaling. RPE cells treated with poly I:C produced IFN-β but not IFN-α, and this was inhibited by the treatment of RPE cells with anti-TLR 3 antibody. Human recombinant IFN-β was shown to be biologically active on RPE cells by inhibiting viral replication. Poly I:C treatment of RPE resulted in an increase in the production of IL-6, IL-8, MCP-1, and sICAM-1. The presence of TLRs on RPE cells and the resultant TLR signaling in RPE cells suggest that these molecules may play an important role in innate and adaptive immune responses within the retina. url: https://api.elsevier.com/content/article/pii/S0165572804001444 doi: 10.1016/j.jneuroim.2004.04.018 id: cord-001901-2s6hpakk author: Kwok, Hoi-Hin title: Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells date: 2016-01-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza A virus (IAV) poses global threats to human health. Acute respiratory distress syndrome and multi-organ dysfunction are major complications in patients with severe influenza infection. This may be explained by the recent studies which highlighted the role of the pulmonary endothelium as the center of innate immune cells recruitment and excessive pro-inflammatory cytokines production. In this report, we examined the potential immunomodulatory effects of two indirubin derivatives, indirubin-3′-(2,3-dihydroxypropyl)-oximether (E804) and indirubin-3′-oxime (E231), on IAV (H9N2) infected-human pulmonary microvascular endothelial cells (HPMECs). Infection of H9N2 on HPMECs induced a high level of chemokines and cytokines production including IP-10, RANTES, IL-6, IFN-β and IFN-γ1. Post-treatment of E804 or E231 could significantly suppress the production of these cytokines. H9N2 infection rapidly triggered the activation of innate immunity through phosphorylation of signaling molecules including mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription (STAT) proteins. Using specific inhibitors or small-interfering RNA, we confirmed that indirubin derivatives can suppress H9N2-induced cytokines production through MAPKs and STAT3 signaling pathways. These results underscore the immunomodulatory effects of indirubin derivatives on pulmonary endothelium and its therapeutic potential on IAV-infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702174/ doi: 10.1038/srep18941 id: cord-256187-ofp7tupv author: Kühl, A. title: How Ebola Virus Counters the Interferon System date: 2012-09-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Zoonotic transmission of Ebola virus (EBOV) to humans causes a severe haemorrhagic fever in afflicted individuals with high case‐fatality rates. Neither vaccines nor therapeutics are at present available to combat EBOV infection, making the virus a potential threat to public health. To devise antiviral strategies, it is important to understand which components of the immune system could be effective against EBOV infection. The interferon (IFN) system constitutes a key innate defence against viral infections and prevents development of lethal disease in mice infected with EBOV strains not adapted to this host. Recent research revealed that expression of the host cell IFN‐inducible transmembrane proteins 1–3 (IFITM1–3) and tetherin is induced by IFN and restricts EBOV infection, at least in cell culture model systems. IFITMs, tetherin and other effector molecules of the IFN system could thus pose a potent barrier against EBOV spread in humans. However, EBOV interferes with signalling events required for human cells to express these proteins. Here, we will review the strategies employed by EBOV to fight the IFN system, and we will discuss how IFITM proteins and tetherin inhibit EBOV infection. url: https://doi.org/10.1111/j.1863-2378.2012.01454.x doi: 10.1111/j.1863-2378.2012.01454.x id: cord-001542-f089bs8r author: Lai, Kang Yiu title: Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus date: 2014-11-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-43) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334593/ doi: 10.1186/2049-9957-3-43 id: cord-290593-vhmi2559 author: Lannes, Nils title: Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses date: 2012-08-30 words: 4412.0 sentences: 250.0 pages: flesch: 49.0 cache: ./cache/cord-290593-vhmi2559.txt txt: ./txt/cord-290593-vhmi2559.txt summary: title: Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. Considering the possible importance of opsonising antibodies and pDC in the protection against FMDV, the main aim of this study was to characterize the relationship between neutralizing and opsonising activities of polyclonal sera from immunized pigs. Plasmacytoid dendritic cell activation by foot-and-mouth disease virus requires immune complexes abstract: Foot-and-mouth disease virus (FMDV) is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses. url: https://doi.org/10.1186/1297-9716-43-64 doi: 10.1186/1297-9716-43-64 id: cord-295684-d3p9nbgq author: Lasfar, Ahmed title: Interferon Lambda: A New Sword in Cancer Immunotherapy date: 2011-12-06 words: 7850.0 sentences: 390.0 pages: flesch: 49.0 cache: ./cache/cord-295684-d3p9nbgq.txt txt: ./txt/cord-295684-d3p9nbgq.txt summary: Experiments showed that similar to their human counterparts, mIFN-λ2 and mIFN-λ3 signal through the IFN-λ receptor complex, activate ISGF3, and are capable of inducing antiviral protection and MHC class I antigen expression in several cell types. IFN-α immunoregulatory functions include major histocompatibility complex (MHC) class I expression in normal and tumor cells, activation of NK cells, dendritic cells (DCs), and macrophages, resulting in the promotion of adaptive immune responses against tumors and virally infected cells [19, 20] . The secretion of constant amounts of various cytokines by transduced tumor cells at the site of tumor growth could elicit more To investigate the potential antitumoral role of IFNλ, we first evaluated the response of B16 melanoma cells to IFN-λ, by analyzing STAT1 activation and MHC class I antigen expression. abstract: The discovery of the interferon-lambda (IFN-λ) family has considerably contributed to our understanding of the role of interferon not only in viral infections but also in cancer. IFN-λ proteins belong to the new type III IFN group. Type III IFN is structurally similar to type II IFN (IFN-γ) but functionally identical to type I IFN (IFN-α/β). However, in contrast to type I or type II IFNs, the response to type III IFN is highly cell-type specific. Only epithelial-like cells and to a lesser extent some immune cells respond to IFN-λ. This particular pattern of response is controlled by the differential expression of the IFN-λ receptor, which, in contrast to IFN-α, should result in limited side effects in patients. Recently, we and other groups have shown in several animal models a potent antitumor role of IFN-λ that will open a new challenging era for the current IFN therapy. url: https://www.ncbi.nlm.nih.gov/pubmed/22190970/ doi: 10.1155/2011/349575 id: cord-353062-c6luoo3m author: Lauber, C title: Transcriptome analysis reveals a classical interferon signature induced by IFNλ4 in human primary cells date: 2015-09-01 words: 5449.0 sentences: 311.0 pages: flesch: 55.0 cache: ./cache/cord-353062-c6luoo3m.txt txt: ./txt/cord-353062-c6luoo3m.txt summary: To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. 23 In order to determine whether IFNλ4 can induce an alternative set of genes, that are not induced in the classical IFN response, we have compared the transcriptional response after IFNα, IFNλ3 and IFNλ4 stimulation in both primary human hepatocytes (PHH) and primary human airway epithelial (HAE) cells using transcriptome sequencing (RNA-seq). Compared with a recently published microarray analysis of type I and type III IFN responses in PHH, which used similar statistical thresholds but substantially higher IFNλ concentrations than our study (1000 ng ml − 1 ), 11 our RNA-seq data provide a more complete estimate of the IFN response (87 versus 50 genes significantly regulated by IFNλ3). abstract: The IFNL4 gene is negatively associated with spontaneous and treatment-induced clearance of hepatitis C virus infection. The activity of IFNλ4 has an important causal role in the pathogenesis, but the molecular details are not fully understood. One possible reason for the detrimental effect of IFNλ4 could be a tissue-specific regulation of an unknown subset of genes. To address both tissue and subtype specificity in the interferon response, we treated primary human hepatocytes and airway epithelial cells with IFNα, IFNλ3 or IFNλ4 and assessed interferon mediated gene regulation using transcriptome sequencing. Our data show a surprisingly similar response to all three subtypes of interferon. We also addressed the tissue specificity of the response, and identified a subset of tissue-specific genes. However, the interferon response is robust in both tissues with the majority of the identified genes being regulated in hepatocytes as well as airway epithelial cells. Thus we provide an in-depth analysis of the liver interferon response seen over an array of interferon subtypes and compare it to the response in the lung epithelium. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/gene.2015.23) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/26066369/ doi: 10.1038/gene.2015.23 id: cord-023445-c4tqioz1 author: Lauridsen, C. title: Supplementation of Vitamin C to Weaner Diets Increases IgM Concentration and Improves the Biological Activity of Vitamin E in Alveolar Macrophages date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Vitamins E and C have been found to increase the cellular and humeral immunity of pigs. Vitamin E deficiency has also been found to predispose pigs to different diseases, E. coli infection is one among them. After weaning, the vitamin E status of pigs often decreases to a critical low level. In this experiment, we studied whether vitamin C supplementation would be a possible feeding strategy to optimize the immune status of weaners. The interaction between vitamin E and C is interesting due to the reported sparing action on vitamin E or synergism between these to vitamins. Piglets were weaned at day 28 of age from sows fed increasing dietary vitamin E during lactation, and piglets were during the following 3 weeks fed either a control diet or this diet supplemented with 500 mg STAY‐C per kg. Blood sampling was obtained weekly from day 28 and until day 49 of age. On the same days, one piglet per dietary treatment was killed and alveolar macrophages (AM) were harvested. Vitamin C supplementation increased the concentration of IgM in serum of piglets throughout the weaning period. Although the vitamin E concentration in AM decreased with increasing age of the piglets, the concentration was numerically higher in piglets of sows fed the high dietary level of vitamin E. However, vitamin C supplementation tended to increase the total AM concentration of vitamin E after weaning and increased the proportion of the biologically most active isomer of vitamin E [RRR‐(α‐tocopherol)] in the AM. The eicosanoid synthesis by AM was not influenced by the vitamin C supplementation, but the synthesis of leukotriene B4 was decreased 2 weeks after weaning compared to other days of AM harvesting. In conclusion, dietary vitamin C supplementation improved the immune responses of piglets after weaning. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169619/ doi: 10.1111/j.0300-9475.2004.01423u.x id: cord-332071-bqvn3ceq author: Lee, Jeong Seok title: Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19 date: 2020-07-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1β-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19. url: https://doi.org/10.1126/sciimmunol.abd1554 doi: 10.1126/sciimmunol.abd1554 id: cord-320338-jv76j6wx author: Lee, Kyungjin title: Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion date: 2017-12-15 words: 5009.0 sentences: 263.0 pages: flesch: 41.0 cache: ./cache/cord-320338-jv76j6wx.txt txt: ./txt/cord-320338-jv76j6wx.txt summary: In this study, we found that the addition of exogenous cytidine, uridine and uridine mono-phosphate (UMP) effectively reversed the antiviral activity of gemcitabine in enterovirus-infected as well as enteroviral replicon-harboring cells, demonstrating gemcitabine''s targeting of the salvage pathway. At first, in order to test if the anti-enteroviral activity of gemcitabine is related with the inhibition of pyrimidine biosynthesis, HeLa cells were infected with CVB3 and simultaneously treated with excessive 4 nucleosides (adenosine, guanosine, uridine and cytidine) in the presence of various doses of gemcitabine for 8 hours. HeLa cells were treated with increasing doses of gemcitabine or IFN-α for 24 hours and then total RNAs were prepared for quantitative real-time PCRs. As a result, gemcitabine strongly induced two genes (IFIT1 and DDX58) up to and UMP) (100 μM) of pyrimidine biosynthetic pathway were treated as described in Figure 1A (A) and in Figure 1B (B) . abstract: Gemcitabine, an anti-cancer chemotherapy drug, has additionally shown the antiviral activity against a broad range of viruses and we also have previously reported its synergistic antiviral activity with ribavirin against enteroviruses. As a cytidine analog, gemcitabine has been reported to have an inhibitory activity on the pyrimidine biosynthesis. In addition, a few inhibitors of the pyrimidine biosynthesis have shown to induce the innate immunity in a yet-to-be-determined manner and inhibit the virus infection. Thus, we also investigated whether the anti-enteroviral activity of gemcitabine is mediated by innate immunity, induction of which is related with the inhibition of the pyrimidine synthesis. In this study, we found that the addition of exogenous cytidine, uridine and uridine mono-phosphate (UMP) effectively reversed the antiviral activity of gemcitabine in enterovirus-infected as well as enteroviral replicon-harboring cells, demonstrating gemcitabine’s targeting of the salvage pathway. Moreover, the expression of several interferon (IFN)-stimulated genes (ISGs) was significantly induced by the treatment of gemcitabine, which was also suppressed by the co-treatment with cytidine. These results suggest that the antiviral activity of gemcitabine involves ISGs induced by the inhibition of the pyrimidine biosynthesis. url: https://doi.org/10.18632/oncotarget.23258 doi: 10.18632/oncotarget.23258 id: cord-308142-3x3n6cpt author: Lee, Nelson title: Chikungunya Fever, Hong Kong date: 2006-11-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/17283640/ doi: 10.3201/eid1211.060574 id: cord-319779-n5w1f0rr author: Lee, Sang-Myeong title: Porcine reproductive and respiratory syndrome virus field isolates differ in in vitro interferon phenotypes date: 2004-12-08 words: 8214.0 sentences: 447.0 pages: flesch: 51.0 cache: ./cache/cord-319779-n5w1f0rr.txt txt: ./txt/cord-319779-n5w1f0rr.txt summary: North American porcine reproductive and respiratory syndrome virus (PRRSV) field isolates were studied with regard to IFN-α sensitivity and induction in order to understand the role of type I IFN in PRRSV pathogenesis. PRRSV isolates were differentially sensitive to porcine recombinant IFN-α (rIFN-α) and varied in their ability to induce IFN-α in porcine alveolar macrophages (PAM) cultures as measured by a porcine IFN-α specific ELISA on cell culture supernatants. In this study, North American field isolates of PRRSV were evaluated with respect to induction, sensitivity and suppression of an in vitro type I IFN response. UV-inactivated PRRSV stocks were tested to determine whether virus binding to the cells is responsible for enhanced IFN-a production by polyI:C in cells infected with isolate 3 (Fig. 6) . In this study, North American PRRSV field isolates were evaluated with respect to induction, sensitivity and suppression of an in vitro IFN response in PAM cultures. Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) abstract: Type I interferons (IFN-α and -β) play an important role in the innate host defense against viral infection by inducing antiviral responses. In addition to direct antiviral activities, type I IFN serves as an important link between the innate and adaptive immune response through multiple mechanisms. Therefore, the outcome of a viral infection can be affected by IFN induction and the IFN sensitivity of a virus. North American porcine reproductive and respiratory syndrome virus (PRRSV) field isolates were studied with regard to IFN-α sensitivity and induction in order to understand the role of type I IFN in PRRSV pathogenesis. PRRSV isolates were differentially sensitive to porcine recombinant IFN-α (rIFN-α) and varied in their ability to induce IFN-α in porcine alveolar macrophages (PAM) cultures as measured by a porcine IFN-α specific ELISA on cell culture supernatants. Fifty-two plaques were purified from three PRRSV isolates (numbers 3, 7, and 12) and tested for IFN sensitivity and IFN induction. Plaque-derived populations were composed of heterogeneous populations in terms of IFN-inducing capacity and sensitivity to rIFN-α. When macrophages infected with isolates 3, 7, or 12 were treated with polycytidylic acid (polyI:C), IFN-α production was enhanced. Cells infected with isolate 3 and treated with polyI:C showed the most consistent and strongest enhancement of IFN-α production. It was demonstrated that the relatively low concentrations of IFN-α produced by isolate 3 contributed to the enhanced IFN-α synthesis in response to polyI:C. Isolates 7 and 12 significantly suppressed the enhanced IFN-α production by isolate 3 in polyI:C treated cells. To determine if suppression was at the level of IFN-α transcription, quantitative RT-PCR was performed for IFN-α mRNA and compared to GAPDH and cyclophilin mRNA quantification. However, the relative number of IFN-α transcript copies did not correlate with IFN-α protein levels, suggesting a post-transcriptional mechanism of suppression. In summary, these results demonstrate that PRRSV field isolates differ both in IFN-α sensitivity and induction. Furthermore, a PRRSV field isolate strongly enhance polyI:C-induced IFN-α production in PAM cultures and this priming effect was suppressed by other PRRSV isolates. url: https://api.elsevier.com/content/article/pii/S0165242704002557 doi: 10.1016/j.vetimm.2004.09.009 id: cord-321947-qek9jy2c author: Lee, Su Jeen title: Evaluation of glycoprotein E subunit and live attenuated varicella‐zoster virus vaccines formulated with a single‐strand RNA‐based adjuvant date: 2020-03-13 words: 5482.0 sentences: 334.0 pages: flesch: 57.0 cache: ./cache/cord-321947-qek9jy2c.txt txt: ./txt/cord-321947-qek9jy2c.txt summary: In VZV-primed mice, we assessed whether this ssRNA adjuvant induces humoral-and cell-mediated immunity in the VZV gE subunit vaccine. However, we used guinea pigs to evaluate the ability of the ssRNA adjuvant to enhance neutralizing antibody production and cell-mediated immune response in VZV LAV. Based on all results, we showed the potential of ssRNA adjuvants to compensate for the limitations of protein-based vaccines with respect to low T-cell activity and short-term responses, as well as to increase the neutralizing antibody in LAV for preventing VZV-induced disease. 41 Here, the ssRNA adjuvant-induced humoral and balanced Th1/Th2 immune responses even though its antibody and cytokine induction levels in the VZV gE protein subunit vaccine were lower than those for AddaVax. Nevertheless, the mode of action of AddaVax has not yet been elucidated. Moreover, the ssRNA derived from CrPV IGR IRES encoding the gE gene, which could express gE in transfected cells, can effectively function as a vaccine adjuvant in a protein-based subunit vaccine by activating humoral and cell-mediated immune responses. abstract: INTRODUCTION: Varicella‐zoster virus (VZV), a human alphaherpesvirus 3, elicits both chickenpox and shingles and/or postherpetic neuralgia. A live attenuated vaccine (LAV) and glycoprotein E (gE) subunit vaccine were developed to prevent VZV‐induced diseases. We recently reported that single‐strand RNA (ssRNA) based on the intergenic region of the internal ribosome entry site of cricket paralysis virus (CrPV) is an effective adjuvant for protein‐based and virus‐like particle‐based vaccines. Here, Chinese hamster ovary expression system and an LAV from Oka/SK strains. METHODS: We appraised the adjuvant effect of the same CrPV ssRNA encoding the gE gene formulated in the two vaccines using VZV‐primed C57BL/6 mice and guinea pigs. Humoral immunity and cell‐mediated immunity were assessed by enzyme‐linked immunosorbent assay (ELISA) and ELISPOT in gE subunit vaccine and by ELISA and fluorescent antibody to membrane antigen in LAV. RESULTS: The gE subunit vaccine‐induced gE‐specific antibodies and CD4(+) T‐cell responses (indicated by interferon‐γ [IFN‐γ] and interleukin‐2 secretion) in the ssRNA‐based adjuvant containing the VZV gE gene. Therefore, an ssRNA adjuvant combined with gE antigen can trigger the innate immune response and induce an adaptive immune response to ultimately activate humoral and cell‐mediated responses. VZV LAV could also induce VZV‐specific antibodies and IFN‐γ stimulated by LAV, whereas the effect of ssRNA as a vaccine adjuvant could not be confirmed. However, the ssRNA adjuvant increased VZV‐specific neutralizing antibody response. CONCLUSIONS: Taken together, these results highlight that the gE subunit vaccine and LAV developed in this study can be functional VZV vaccines, and ssRNAs appear to function better as adjuvants in a subunit vaccine than in an LAV. url: https://doi.org/10.1002/iid3.297 doi: 10.1002/iid3.297 id: cord-333286-lr32e0w4 author: Lehtoranta, Liisa title: Role of Probiotics in Stimulating the Immune System in Viral Respiratory Tract Infections: A Narrative Review date: 2020-10-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viral respiratory tract infection (RTI) is the most frequent cause of infectious illnesses including the common cold. Pharmacological solutions for treating or preventing viral RTIs are so far limited and thus several self-care products are available in the market. Some dietary supplements such as probiotics have been shown to modulate immune system function and their role in reducing the risk and the course of RTIs has been investigated extensively within the past decade. However, the mechanism of action and the efficacy of probiotics against viral RTIs remains unclear. We searched PubMed, Google Scholar, and Web of Knowledge for pre-clinical and clinical studies investigating the effect of probiotics on respiratory virus infections, immune response, and the course of upper and lower respiratory tract illness. The literature summarized in this narrative review points out that specific probiotic strains seem effective in pre-clinical models, through stimulating the immune system and inhibiting viral replication. Clinical studies indicate variable efficacy on upper respiratory illnesses and lack proof of diagnosed viral infections. However, meta-analyses of clinical studies indicate that probiotics could be beneficial in upper respiratory illnesses without specific etiology. Further studies aiming at discovering the mechanisms of action of probiotics and clinical efficacy are warranted. url: https://doi.org/10.3390/nu12103163 doi: 10.3390/nu12103163 id: cord-310396-jitao9k0 author: Lei, Yu title: MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins date: 2009-03-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Host responses to viral infection include both immune activation and programmed cell death. The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated. PRINCIPAL FINDINGS: We show that MAVS causes apoptosis independent of its function in initiating IFN-I production. MAVS-induced cell death requires mitochondrial localization, is caspase dependent, and displays hallmarks of apoptosis. Furthermore, MAVS(−/−) fibroblasts are resistant to Sendai virus-induced apoptosis. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion. SIGNIFICANCE: This study describes a novel role for MAVS in controlling viral infections through the induction of apoptosis, and identifies viral proteins which inhibit this host response. url: https://doi.org/10.1371/journal.pone.0005466 doi: 10.1371/journal.pone.0005466 id: cord-286328-ap0wfjhq author: Lewis, Toby C. title: Nasal cytokine responses to natural colds in asthmatic children date: 2012-11-26 words: 4776.0 sentences: 260.0 pages: flesch: 46.0 cache: ./cache/cord-286328-ap0wfjhq.txt txt: ./txt/cord-286328-ap0wfjhq.txt summary: CONCLUSIONS & CLINICAL RELEVANCE: We conclude that, in children with asthma, naturally-occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs and IFN-responsive genes. To further examine the innate immune response to viral infection in children with asthma, we measured nasal aspirate cytokine levels in 16 asthmatic children before and after upper respiratory tract infections. We also examined the effects of upper respiratory tract infection on mRNA levels of selected markers of viral infection, including IFNs. Finally, we evaluated a new method of virus detection using a single polymerase chain reaction-ligation detection reaction (PCR-LDR) multiplex assay. We performed home measurements of respiratory symptoms and collected nasal secretions (for detection of viral RNA by PCR and host biomarkers by PCR and ELISA) on 3 days during a week when children were healthy (not reporting upper respiratory tract infection or asthma symptoms), and again during a week when they experienced cold or flu-like symptoms. abstract: BACKGROUND: The mechanisms by which viruses induce asthma exacerbations are not well-understood. OBJECTIVE: We characterized fluctuations in nasal aspirate cytokines during naturally-occurring respiratory viral infections in children with asthma. METHODS: Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured by multiplex immune assay. mRNA expression for selected markers of viral infection was measured by RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score. RESULTS: The 16 patients completed a total of 37 weeks of assessment (15 “well” weeks; 22 self-assessed “sick” weeks). Viral infections were detected in three of the “well” weeks and 17 of the “sick” weeks (10 rhinovirus, 3 coronavirus, 2 influenza A, 2 influenza B, 2 respiratory syncytial virus, 1 parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1β, CCL7/MCP-3 and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5 and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I and IRF7 mRNA. CONCLUSIONS & CLINICAL RELEVANCE: We conclude that, in children with asthma, naturally-occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs and IFN-responsive genes. url: https://deepblue.lib.umich.edu/bitstream/2027.42/94448/1/cea12005.pdf doi: 10.1111/cea.12005 id: cord-302401-oyhzn2kc author: Li, Chenxi title: Duck karyopherin α4 (duKPNA4) is involved in type I interferon expression and the antiviral response against Japanese encephalitis virus date: 2019-11-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Karyopherin α4 (KPNA4) is an adaptor molecule that mediates type I interferon (IFN) production by facilitating the nuclear translocation of IFN transcription factors. Here, we cloned the duck KPNA4 (duKPNA4) gene and analyzed its involvement in type I IFN expression as well as antiviral response against Japanese encephalitis virus (JEV). The full-length duKPNA4 gene encoded a 520-amino acid protein that shared 97.3–98.7% sequence similarity with its orthologues in chickens, humans and mice. The duKPNA4 was extensively expressed in various duck tissues at the mRNA level. Analysis of the subcellular localization of duKPNA4 by immunofluorescence assays indicated that the duKPNA4 was primarily distributed in both the cytoplasm and nucleus in primary duck embryonic fibroblasts (DEFs). However, it translocated from the cytoplasm to the nucleus in response to poly(I:C) stimulation or JEV infection. The duKPNA4 interacted with duck IFN regulatory factor 7 and facilitated its nuclear translocation, thereby up-regulating the expression of IFN-α and IFN-β in DEFs in the presence of poly(I:C) stimulation. Exogenous expression of duKPNA4 significantly elevated the expression of IFN-α and IFN-β induced by JEV infection and inhibited JEV replication in DEFs. These data demonstrate the importance of duKPNA4 in type I IFN signaling as well as the antiviral response against JEV replication. url: https://doi.org/10.1016/j.dci.2019.103535 doi: 10.1016/j.dci.2019.103535 id: cord-278018-3qemb0x3 author: Li, Li title: Identification of M.tuberculosis-Specific Th1 Cells Expressing CD69 Generated in vivo in Pleural Fluid Cells from Patients with Tuberculous Pleurisy date: 2011-08-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Th1 cell-mediated immune responses at the site of active infection are important to restrict the growth of M.tuberculosis (MTB) and for the spontaneous resolution of patients with tuberculous pleurisy (TBP). In the present study, we found that without any stimulation, CD4(+) T cells in pleural fluid cells (PFCs) from patients with TBP expressed significantly higher levels of CD69 than PBMCs from patients with tuberculosis (TB) or healthy donors. CD4(+)CD69(+) T cells expressed T-bet and IL-12Rβ2. After stimulation with MTB-specific antigens, CD4(+)CD69(+) T cells expressed significantly higher levels of IFN-γ, IL-2 and TNF-α than CD4(+)CD69(−) T cells, demonstrating that CD4(+)CD69(+) T cells were MTB-specific Th1 cells. In addition, CD4(+)CD69(+) T cells were mostly polyfunctional Th1 cells that simultaneously produced IFN-γ, IL-2, TNF-α and displayed an effector or effector memory phenotype (CD45RA(−)CCR7(−)CD62L(−)CD27(−)). Moreover, the percentages of CD4(+)CD69(+) T cells were significantly and positively correlated with polyfunctional T cells. Interestingly, sorted CD4(+)CD69(+) but not CD4(+)CD69(−) fractions by flow cytometry produced IFN-γ, IL-2 and TNF-α that were significantly regulated by CD4(+)CD25(+) Treg cells. Taken together, based on the expression of CD69, we found a direct quantitative and qualitative method to detect and evaluate the in vivo generated MTB-specific polyfunctional CD4(+) T cells in PFCs from patients with TBP. This method can be used for the potential diagnosis and enrichment or isolation of MTB-specific Th1 cells in the investigations. url: https://doi.org/10.1371/journal.pone.0023700 doi: 10.1371/journal.pone.0023700 id: cord-254192-86ksgl5t author: Li, Liang title: IFN-Lambda 3 Mediates Antiviral Protection Against Porcine Epidemic Diarrhea Virus by Inducing a Distinct Antiviral Transcript Profile in Porcine Intestinal Epithelia date: 2019-10-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Type III interferon-lambda (IFN-λ) plays a critical role against infection, particularly in mucosal infection in the respiratory and gastrointestinal tract. Our study and other previous studies have shown that porcine IFN-λ more efficiently curtails the infection of porcine epidemic diarrhea virus (PEDV) in the intestine epithelia than type I IFN, whereas IFN-λ3 exerts a more potent effect than IFN-λ1. However, the underlying mechanism remains elusive, and in particular, the transcriptional profile induced by IFN-λ3 has not been reported. Here, to resolve the mechanism responsible for the disparity between IFN-λ3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-λ3 resulted in the differential expression of 983 genes. In contrast, IFN-α only modified the expression of 134 genes, and 110 of these genes were also observed in the response to IFN-λ3. A transcriptional enrichment analysis indicated that IFN-λ3 or IFN-α regulates multiple cellular processes and that IFN-λ3 activates more robust signaling pathways, particularly the antiviral Jak-STAT signaling pathway, than IFN-α. Furthermore, we verified the RNA-Seq results through an RT-qPCR analysis of IPEC-J2 cells and porcine enteroids. Moreover, transient expression of the porcine rsad2 and mx2 genes among the top 10 genes induced by IFN-λ3 significantly inhibited PEDV infection. Collectively, the data showed that IFN-λ3 induces a unique transcriptional profile that does not completely overlap with that induced by IFN-α and strongly elicits a set of genes responsible for the antiviral activity of IFN-λ3. These findings provide important knowledge regarding the elicited ISGs of type I and III IFNs in restricting porcine intestinal viral infection. url: https://doi.org/10.3389/fimmu.2019.02394 doi: 10.3389/fimmu.2019.02394 id: cord-309428-qkjjxr6p author: Li, Liwei title: Host miR-26a suppresses replication of porcine reproductive and respiratory syndrome virus by upregulating type I interferons date: 2015-01-02 words: 5084.0 sentences: 324.0 pages: flesch: 53.0 cache: ./cache/cord-309428-qkjjxr6p.txt txt: ./txt/cord-309428-qkjjxr6p.txt summary: MicroRNAs (miRNAs) play important roles in viral infections, especially by modulating the expression of cellular factors essential to viral replication or the host innate immune response to infection. To identify host miRNAs important to controlling porcine reproductive and respiratory syndrome virus (PRRSV) infection, we screened 15 miRNAs that were previously implicated in innate immunity or antiviral functions. Luciferase reporters showed that miR-26a does not target the PRRSV genome directly but instead affects the expression of type I interferon and the IFN-stimulated genes MX1 and ISG15 during PRRSV infection. We found that miR-26a does not target the PRRSV genome directly, but rather affects the expression of type I interferon and the IFN-stimulated genes MX1 and ISG15 during PRRSV infection. Indirect immunofluorescence assays (IFA) were performed as described previously (Tian et al., 2011) for the detection of nucleocapsid (N) protein in PRRSV vJX143 infected MARC-145 cells or PAMs pre-transfected with miR-26 family or mutant mimics. abstract: MicroRNAs (miRNAs) play important roles in viral infections, especially by modulating the expression of cellular factors essential to viral replication or the host innate immune response to infection. To identify host miRNAs important to controlling porcine reproductive and respiratory syndrome virus (PRRSV) infection, we screened 15 miRNAs that were previously implicated in innate immunity or antiviral functions. Over-expression of the miR-26 family strongly inhibited PRRSV replication in vitro, as shown by virus titer assays, Western blotting, and qRT-PCR assays. MiR-26a inhibited the replication of both type 1 and type 2 PRRSV strains. Mutating the seed region of miR-26 restored viral titers. Luciferase reporters showed that miR-26a does not target the PRRSV genome directly but instead affects the expression of type I interferon and the IFN-stimulated genes MX1 and ISG15 during PRRSV infection. These results demonstrate the important role of miR-26a in modulating PRRSV infection and also support the possibility of using host miR-26a to achieve RNAi-mediated antiviral therapeutic strategies. url: https://www.sciencedirect.com/science/article/pii/S0168170214003402 doi: 10.1016/j.virusres.2014.08.012 id: cord-327000-oyg3oyx1 author: Li, Shasha title: Porcine Epidemic Diarrhea Virus and the Host Innate Immune Response date: 2020-05-11 words: 11098.0 sentences: 688.0 pages: flesch: 48.0 cache: ./cache/cord-327000-oyg3oyx1.txt txt: ./txt/cord-327000-oyg3oyx1.txt summary: This review highlights the immune evasion mechanisms employed by PEDV, which provides insights for the better understanding of PEDV-host interactions and developing effective vaccines and antivirals against CoVs. Porcine epidemic diarrhea virus (PEDV) is the etiological agent of porcine epidemic diarrhea (PED) that causes an acute and highly contagious enteric disease of swine characterized by vomiting, diarrhea, dehydration, and anorexia in pigs of all ages, especially resulting in severe diarrhea and high mortality rate in piglets. Nsp3 is the largest nsp protein, containing two papain-like protease (PLP1 and PLP2) domains, of which PEDV PLP2 acts as a viral deubiquitinase (DUB), to negatively regulate type I IFN signaling [80] . The evasive strategies utilized by PEDV are classified into four major types: (1) inhibition of RLRs-mediated IFN production pathways, (2) inhibition of the activation of transcription factors responsible for IFN induction, (3) disruption of the signal cascades induced by IFN, and (4) hiding its viral RNA to avoid the exposure of viral RNA to immune sensors. abstract: Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus (CoV), is the causative agent of porcine epidemic diarrhea (PED). PED causes lethal watery diarrhea in piglets, which has led to substantial economic losses in many countries and is a great threat to the global swine industry. Interferons (IFNs) are major cytokines involved in host innate immune defense, which induce the expression of a broad range of antiviral effectors that help host to control and antagonize viral infections. PEDV infection does not elicit a robust IFN response, and some of the mechanisms used by the virus to counteract the host innate immune response have been unraveled. PEDV evades the host innate immune response by two main strategies including: 1) encoding IFN antagonists to disrupt innate immune pathway, and 2) hiding its viral RNA to avoid the exposure of viral RNA to immune sensors. This review highlights the immune evasion mechanisms employed by PEDV, which provides insights for the better understanding of PEDV-host interactions and developing effective vaccines and antivirals against CoVs. url: https://doi.org/10.3390/pathogens9050367 doi: 10.3390/pathogens9050367 id: cord-276166-b1e0bbrp author: Li, Shi-fang title: Interferon-omega: Current status in clinical applications date: 2017-10-12 words: 7734.0 sentences: 365.0 pages: flesch: 45.0 cache: ./cache/cord-276166-b1e0bbrp.txt txt: ./txt/cord-276166-b1e0bbrp.txt summary: Previous studies showed that glycosylated IFN-ω + ribavirin (RBV) had a synergistic effect in terms of its antiviral activity in hepatitis C virus (HCV)-infected patients [43] . [49] showed that interleukin (IL)-6 production was affected considerably in feline immunodeficiency virus (FIV)-infected cats treated with recombinant feline IFN-ω (rFeIFN-ω) by subcutaneous or oral protocols. Because of its antiviral, immunomodulatory, anti-proliferation, and antitumor activities, IFN-ω has been explored as a treatment option for some diseases and viral infections in humans and other animals. Evaluation of viremia, proviral load and cytokine profile in naturally feline immunodeficiency virus infected cats treated with two different protocols of recombinant feline interferon omega Limited efficacy of topical recombinant feline interferon-omega for treatment of cats with acute upper respiratory viral disease Oral recombinant feline interferon-omega as an alternative immune modulation therapy in FIV positive cats: clinical and laboratory evaluation abstract: Since 1985, interferon (IFN)-ω, a type I IFN, has been identified in many animals, but not canines and mice. It has been demonstrated to have antiviral, anti-proliferation, and antitumor activities that are similar to those of IFN-α. To date, IFN-ω has been explored as a treatment option for some diseases or viral infections in humans and other animals. Studies have revealed that human IFN-ω displays antitumor activities in some models of human cancer cells and that it can be used to diagnose some diseases. While recombinant feline IFN-ω has been licensed in several countries for treating canine parvovirus, feline leukemia virus, and feline immunodeficiency virus infections, it also exhibits a certain efficacy when used to treat other viral infections or diseases. This review examines the known biological activity of IFN-ω and its clinical applications. We expect that the information provided in this review will stimulate further studies of IFN-ω as a therapeutic agent. url: https://www.sciencedirect.com/science/article/pii/S1567576917303351 doi: 10.1016/j.intimp.2017.08.028 id: cord-288960-v6l6o5va author: Li, Yang title: Regulating STING in health and disease date: 2017-06-07 words: 12297.0 sentences: 689.0 pages: flesch: 41.0 cache: ./cache/cord-288960-v6l6o5va.txt txt: ./txt/cord-288960-v6l6o5va.txt summary: Possibly via RIG-I -dependent RNA detection which may in turn induce STING [6] Vesicular stomatitis virus Negative strand ssRNA virus Unknown [6] Human immunodeficiency virus Negative strand ssRNA virus dsDNA reverse transcribed from viral RNA induces cGAS-STING pathway [28] Influenza A virus Negative strand ssRNA virus Possibly via membrane fusion or unknown mechanism independent of DNA recognition [29] Mycobacteria tuberculosis Bacteria producing c-di-GMP c-di-GMP [30, 31] Streptococcus pneumoniae Bacteria dsDNA Bacterial dsDNA [32] Streptococcus pyrogenes Bacteria dsDNA Bacterial dsDNA [33] Staphylococcus aureus Bacteria producing c-di-AMP c-di-AMP [34] Listeria monocytogenes Bacteria producing c-di-AMP c-di-AMP [35] Vibrio cholera Bacteria producing 3′-3′ cGAMP 3′-3′ cGAMP [36, 37] Abbreviations: dsDNA double-stranded DNA, ssRNA single-stranded RNA The type I interferon signal adaptor protein STING is responsible for mediating double-stranded DNA sensing responses and the detection of bacterial cyclic dinucleotides c-di-AMP, c-di-GMP, and 3′-3′ cGAMP. abstract: The presence of cytosolic double-stranded DNA molecules can trigger multiple innate immune signalling pathways which converge on the activation of an ER-resident innate immune adaptor named “STimulator of INterferon Genes (STING)”. STING has been found to mediate type I interferon response downstream of cyclic dinucleotides and a number of DNA and RNA inducing signalling pathway. In addition to its physiological function, a rapidly increasing body of literature highlights the role for STING in human disease where variants of the STING proteins, as well as dysregulated STING signalling, have been implicated in a number of inflammatory diseases. This review will summarise the recent structural and functional findings of STING, and discuss how STING research has promoted the development of novel therapeutic approaches and experimental tools to improve treatment of tumour and autoimmune diseases. url: https://doi.org/10.1186/s12950-017-0159-2 doi: 10.1186/s12950-017-0159-2 id: cord-011436-ud35mf5l author: Li, Yingying title: Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation date: 2020-04-06 words: 7446.0 sentences: 451.0 pages: flesch: 56.0 cache: ./cache/cord-011436-ud35mf5l.txt txt: ./txt/cord-011436-ud35mf5l.txt summary: It was also found that rRABVs expressing IFN-λ could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. To further characterize the role of IFN-λ in RABV infection in the mouse model, recombinant RABVs (rRABVs) expressing murine IFN-λ2 or IFN-λ3, designated as rB2c-IFNλ2 and rB2c-IFNλ3 respectively, were constructed as shown in Figure 2A , and rescued as described previously [27] . To further investigate whether IFN-λ restricts RABV infection in vivo, groups of five-week-old female BALB/c mice were mock-infected with DMEM or inoculated with B2c, rB2c-IFNλ2, or rB2c-IFNλ3 by different routes. Expression of neuronal CXCL10 induced by rabies virus infection initiates infiltration of inflammatory cells, production of chemokines and cytokines, and enhancement of blood-brain barrier permeability abstract: Rabies, caused by rabies virus (RABV), is a fatal neurological disease that still causes more than 59,000 human deaths each year. Type III interferon IFN-λs are cytokines with type I IFN-like antiviral activities. Although IFN-λ can restrict the infection for some viruses, especially intestinal viruses, the inhibitory effect against RABV infection remains undefined. In this study, the function of type III IFN against RABV infection was investigated. Initially, we found that IFN-λ2 and IFN-λ3 could inhibit RABV replication in cells. To characterize the role of IFN-λ in RABV infection in a mouse model, recombinant RABVs expressing murine IFN-λ2 or IFN-λ3, termed as rB2c-IFNλ2 or rB2c-IFNλ3, respectively, were constructed and rescued. It was found that expression of IFN-λ could reduce the pathogenicity of RABV and limit viral spread in the brains by different infection routes. Furthermore, expression of IFN-λ could induce the activation of the JAK-STAT pathway, resulting in the production of interferon-stimulated genes (ISGs). It was also found that rRABVs expressing IFN-λ could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. Consistently, IFN-λ was found to maintain the integrity of tight junction (TJ) protein ZO-1 of BBB to alleviate neuroinflammation in a transwell model. Our study underscores the role of IFN-λ in inhibiting RABV infection, which potentiates IFN-λ as a possible therapeutic agent for the treatment of RABV infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232327/ doi: 10.3390/v12040405 id: cord-007796-zggk0x2q author: Lindemans, Caroline A. title: The Immune Response to Viral Lower Respiratory Tract Infection date: 2005 words: 9767.0 sentences: 518.0 pages: flesch: 38.0 cache: ./cache/cord-007796-zggk0x2q.txt txt: ./txt/cord-007796-zggk0x2q.txt summary: In respect to the role of viruses in the pathogenesis of acute and chronic airway disease in children, it is of utmost importance that we gain a proper understanding of the underlying mechanisms involved in order to design effective therapeutic and preventive strategies. Epithelial cells are key regulators of the innate immune response against viral infections (Garofalo and Haeberle, 2000) , producing a number of inflammatory mediators in response to RSV infection. In summary, in RSV lower respiratory tract infections, cytotoxic CD8ϩ T-cells are involved in viral clearance while the humoral response is required for the protection against reinfection. The innate immune defense to viral respiratory tract infections consists of the mucosal layer, type 1 interferons, activated phagocytes, and NK-cells. A key question is whether the association with the development of asthma is merely an expression of increased susceptibility to both asthma and RSV-induced lower respiratory tract infections or whether true causality is involved. abstract: Viruses are responsible for the majority of respiratory infections in childhood,causing considerable morbidity and mortality. It is estimated that in the United States approximately $ 652 million per year is spent on medical costs for respiratory syncytial virus (RSV) related disease alone (Paramore et al., 2004). Viruses cause a variety of respiratory diseases in children from the common cold to life-threatening pneumonia and bronchiolitis. The host reacts to a viral infection with a combination of innate and adaptive immune mechanisms, usually resulting in the clearance of the virus and clinical recovery. However, there is an accumulating evidence for a number of viral infections that the host immune response actually enhances disease in the course of clearing virus from the infected organs. Interestingly, the effectiveness of the immune response seems to be dependent on the age and probably genetic background of the child. This has important implications for treatment as well as vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123507/ doi: 10.1007/0-387-25342-4_4 id: cord-003130-p2h8p5bm author: Lindqvist, Richard title: Tick-Borne Flaviviruses and the Type I Interferon Response date: 2018-06-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Flaviviruses are globally distributed pathogens causing millions of human infections every year. Flaviviruses are arthropod-borne viruses and are mainly transmitted by either ticks or mosquitoes. Mosquito-borne flaviviruses and their interactions with the innate immune response have been well-studied and reviewed extensively, thus this review will discuss tick-borne flaviviruses and their interactions with the host innate immune response. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071234/ doi: 10.3390/v10070340 id: cord-348684-xbxwpmxq author: Liu, Bao-qin title: Ubiquitination modification: critical regulation of IRF family stability and activity date: 2020-10-30 words: 5231.0 sentences: 258.0 pages: flesch: 32.0 cache: ./cache/cord-348684-xbxwpmxq.txt txt: ./txt/cord-348684-xbxwpmxq.txt summary: Interferon regulatory factors (IRFs) play pivotal and critical roles in innate and adaptive immune responses; thus, precise and stringent regulation of the stability and activation of IRFs in physiological processes is necessary. Knowledge of how these proteins function and interact with IRFs may provide a better understanding of the regulation of IRFs in immune responses or other biological processes and exciting targets for the development of drugs aimed at regulating the functions of specific E3 ligases or DUBs. Ubiquitination is a type of reversible cellular protein PTM. Furthermore, K63-linked polyubiquitination and monoubiquitination, the second most common type of ubiquitin linkage, mediate proteasome-independent effects, which play an important role in activating many components of different signaling pathways and participate in many biological processes (Ning et al., 2011) . c-Cbl, a member of the Cbl (Casitas B-lineage lymphoma) family, negatively regulates IRF3 protein stability by interacting with the C-terminal domain of IRF3 via its TKB (tyrosine kinase binding) domain and promotes K48-linked polyubiquitination-dependent proteasomal degradation of IRF3 (Zhao et al., 2016) . abstract: Interferon regulatory factors (IRFs) play pivotal and critical roles in innate and adaptive immune responses; thus, precise and stringent regulation of the stability and activation of IRFs in physiological processes is necessary. The stability and activities of IRFs are directly or indirectly targeted by endogenous and exogenous proteins in an ubiquitin-dependent manner. However, few reviews have summarized how host E3 ligases/DUBs or viral proteins regulate IRF stability and activity. Additionally, with recent technological developments, details about the ubiquitination of IRFs have been continuously revealed. As knowledge of how these proteins function and interact with IRFs may facilitate a better understanding of the regulation of IRFs in immune responses or other biological processes, we summarized current studies on the direct ubiquitination of IRFs, with an emphasis on how these proteins interact with IRFs and affect their activities, which may provide exciting targets for drug development by regulating the functions of specific E3 ligases. url: https://www.ncbi.nlm.nih.gov/pubmed/33141302/ doi: 10.1007/s11427-020-1796-0 id: cord-007654-lchdm4xr author: Liu, Yang title: Flavivirus infection up-regulates the expression of class I and class II major histocompatibility antigens on and enhances T cell recognition of astrocytes in vitro date: 2002-12-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: West Nile virus (WNV) infection of astrocytes can up-regulate their expression of both class I and class II major histocompatibility complex (MHC) antigens as determined by flow cytometry with monoclonal antibodies specific for class I and class II MHC antigens. The up-regulation of class I MHC antigen expression could be partly caused by interferon secreted after WNV infection because the synthetic interferon inducer polyinosinic-polycytidylic acid (poly I : C) has similar effects. In contrast the up-regulation of class II MHC antigen expression was not induced by poly I : C. The increased MHC antigen expression by WNV infection had significant effects on T cell recognition. Thus, WNV and influenza virus A/WSN double-infected astrocytes but not astrocytes infected by A/WSN alone were lysed by influenza virus-immune cytotoxic T cells. Similarly, WNV-infected astrocytes were better stimulators than normal astrocytes for a class II MHC-reactive T cell line, both in terms of T cell proliferation and interleukin release. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119853/ doi: 10.1016/0165-5728(89)90171-9 id: cord-310469-v4p01rze author: Livonesi, Márcia Cristina title: In vitro and in vivo studies of the Interferon-alpha action on distinct Orthobunyavirus date: 2007-02-28 words: 4271.0 sentences: 244.0 pages: flesch: 60.0 cache: ./cache/cord-310469-v4p01rze.txt txt: ./txt/cord-310469-v4p01rze.txt summary: Thus, in an effort to characterize antiviral agents that could attenuate infections caused by OROV, CARV, GMAV, GROV and TCMV, we tested the in vitro and in vivo actions of IFN-␣ on these viruses. However, treatment of CARV-, GMAV-or TCMV-infected mice with IFN-␣A did not result in an increase in survival or prolongation of the mean time to death and did not prevent virus replication in the brain of animals (Table 2 and Fig. 3, respectively) . Treatment with IFN-␣A initiated 24 h after mice infection by GROV was unable to inhibit either the death of animals or the viral replication in the brain (Table 3 and Fig. 5 , respectively). In vitro and in vivo results showed that IFN-␣ was able to prevent viral replication in a limited manner, exerting antiviral effect only when administrated early and in high doses, suggesting that OROV, CARV, GMAV, GROV and TCMV present some escape mechanism from antiviral actions of the IFN-␣. abstract: Oropouche, Caraparu, Guama, Guaroa and Tacaiuma viruses (Orthobunyavirus genus) cause human febrile illnesses and/or encephalitis. To achieve a therapeutical agent to prevent and/or treat these diseases we evaluated the antiviral action of Interferon-alpha (IFN-α) on these orthobunyaviruses. In vitro results showed that all the studied orthobunyaviruses are susceptible to antiviral action of IFN-α, but this susceptibility is limited and dependent on both concentration of drug and treatment period. In vivo results demonstrated that IFN-α present antiviral action on Oropouche and Guaroa viruses when used as a prophylactic treatment. Moreover, a treatment initiated 3 h after infection prevented the death of Guaroa virus infected-mice. Additionally, mortality of mice was related to the migration and replication of viruses in their brains. Our results suggest that IFN-α could be potentially useful in the prevention of diseases caused by Oropouche virus and in the prevention and/or treatment of diseases caused by Guaroa virus. url: https://www.ncbi.nlm.nih.gov/pubmed/17368573/ doi: 10.1016/j.antiviral.2007.01.158 id: cord-335384-co2fgz26 author: Lobo‐Silva, Diogo title: Interferon‐β regulates the production of IL‐10 by toll‐like receptor‐activated microglia date: 2017-06-15 words: 7144.0 sentences: 385.0 pages: flesch: 50.0 cache: ./cache/cord-335384-co2fgz26.txt txt: ./txt/cord-335384-co2fgz26.txt summary: These differential responses were not dependent on the dose of agonist used to stimulate microglia, as increasing the doses of TLR ligands did not result in enhanced secretion of IL-10, nor of TNF (Supporting Information, Figure 1 ). Considering the cytokine landscape obtained upon TLR3 triggering of microglia (Figure 1 ), if such mechanism was operating, the best candidate molecule would be IFN-b, as it is strongly induced by TLR3 ( Figure 1g ) and it has been described to potentiate IL-10 in studies performed with bone marrow-derived macrophages and dendritic cells (Iyer, Ghaffari, & Cheng, 2010; F. Co-stimulation of microglia with TLR3 enhanced IL-10 production via IFN-b, thus opening a novel mechanism underlying its beneficial role in MS and being a possible tool to locally regulate inflammatory responses. abstract: Pattern recognition receptors, such as toll‐like receptors (TLRs), perceive tissue alterations and initiate local innate immune responses. Microglia, the resident macrophages of the brain, encode TLRs which primary role is to protect the tissue integrity. However, deregulated activation of TLRs in microglia may lead to chronic neurodegeneration. This double role of microglial responses is often reported in immune‐driven neurologic diseases, as in multiple sclerosis (MS). Consequently, strategies to manipulate microglia inflammatory responses may help to ameliorate disease progression. In this context, the anti‐inflammatory cytokine interleukin (IL)‐10 appears as an attractive target. In this study, we investigated how activation of microglia by TLRs with distinct roles in MS impacts on IL‐10 production. We found that activation of TLR2, TLR4, and TLR9 induced the production of IL‐10 to a greater extent than activation of TLR3. This was surprising as both TLR3 and IL‐10 play protective roles in animal models of MS. Interestingly, combination of TLR3 triggering with the other TLRs, enhanced IL‐10 through the modulation of its transcription, via interferon (IFN)‐β, but independently of IL‐27. Thus, in addition to the modulation of inflammatory responses of the periphery described for the axis TLR3/IFN‐β, we now report a direct modulation of microglial responses. We further show that the presence of IFN‐γ in the microenvironment abrogated the modulation of IL‐10 by TLR3, whereas that of IL‐17 had no effect. Considering the therapeutic application of IFN‐β in MS, our study bears important implications for the understanding of the cytokine network regulating microglia responses in this setting. url: https://www.ncbi.nlm.nih.gov/pubmed/28617991/ doi: 10.1002/glia.23172 id: cord-279733-c0w9bw5u author: Lui, Pak-Yin title: Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 date: 2016-04-20 words: 5238.0 sentences: 281.0 pages: flesch: 48.0 cache: ./cache/cord-279733-c0w9bw5u.txt txt: ./txt/cord-279733-c0w9bw5u.txt summary: title: Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response. In non-specialized epithelial cells as well as a subset of specialized immune cells that are susceptible to MERS-CoV infection, 16, 18, 27 type I IFN production is an important part of the host innate immune response and is initiated by ubiquitously expressed cytoplasmic viral sensors in the retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) family in response to the detection of viral pathogen-associated molecular patterns such as double-stranded RNA (dsRNA). Middle east respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in the innate antiviral response abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-encoded proteins were identified to have interferon (IFN)-antagonizing properties, which correlates well with the reduced IFN levels observed in infected patients and ex vivo models. In this study, we fully characterized the IFN-antagonizing property of the MERS-CoV M protein. Expression of MERS-CoV M protein suppressed type I IFN expression in response to Sendai virus infection or poly(I:C) induction. This suppressive effect was found to be specific for the activation of IFN regulatory factor 3 (IRF3) but not nuclear factor-κB. MERS-CoV M protein interacted with TRAF3 and disrupted TRAF3–TBK1 association leading to reduced IRF3 activation. M proteins from MERS-CoV and SARS-CoV have three highly similar conserved N-terminal transmembrane domains and a C-terminal region. Using chimeric and truncation mutants, the N-terminal transmembrane domains of the MERS-CoV M protein were found to be sufficient for its inhibitory effect on IFN expression, whereas the C-terminal domain was unable to induce this suppression. Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response. url: https://www.ncbi.nlm.nih.gov/pubmed/27094905/ doi: 10.1038/emi.2016.33 id: cord-332632-u2ud0vmq author: Lussi, Carmela title: What can pestiviral endonucleases teach us about innate immunotolerance? date: 2016-03-17 words: 8703.0 sentences: 394.0 pages: flesch: 44.0 cache: ./cache/cord-332632-u2ud0vmq.txt txt: ./txt/cord-332632-u2ud0vmq.txt summary: In particular, the unique extension of ''self'' to include the viral genome by degrading immunostimulatory viral RNA by E(rns) is reminiscent of various host nucleases that are important to prevent inappropriate IFN activation by the host''s own nucleic acids in autoimmune diseases such as Aicardi-Goutières syndrome or systemic lupus erythematosus. Thus, the survival strategy of BVDV consists of being non-cytopathogenic and producing less dsRNA than its cp counterpart, and expressing the IFN antagonists N pro as the first protein in order to reduce or even avoid IFN production in infected cells and E rns to degrade immunostimulatory viral RNA before they might activate the host''s PRRs. Notably, both pestiviral IFN antagonists are not only required to constantly maintain innate immunotolerance during persistent infections, but they also play an important role in acute infections [25] . abstract: Pestiviruses including bovine viral diarrhea virus (BVDV), border disease virus (BDV) and classical swine fever virus (CSFV), occur worldwide and are important pathogens of livestock. A large part of their success can be attributed to the induction of central immunotolerance including B- and T-cells upon fetal infection leading to the generation of persistently infected (PI) animals. In the past few years, it became evident that evasion of innate immunity is a central element to induce and maintain persistent infection. Hence, the viral non-structural protease N(pro) heads the transcription factor IRF-3 for proteasomal degradation, whereas an extracellularly secreted, soluble form of the envelope glycoprotein E(rns) degrades immunostimulatory viral single- and double-stranded RNA, which makes this RNase unique among viral endoribonucleases. We propose that these pestiviral interferon (IFN) antagonists maintain a state of innate immunotolerance mainly pertaining its viral nucleic acids, in contrast to the well-established immunotolerance of the adaptive immune system, which is mainly targeted at proteins. In particular, the unique extension of ‘self’ to include the viral genome by degrading immunostimulatory viral RNA by E(rns) is reminiscent of various host nucleases that are important to prevent inappropriate IFN activation by the host’s own nucleic acids in autoimmune diseases such as Aicardi-Goutières syndrome or systemic lupus erythematosus. This mechanism of “innate tolerance” might thus provide a new facet to the role of extracellular RNases in the sustained prevention of the body’s own immunostimulatory RNA to act as a danger-associated molecular pattern that is relevant across various species. url: https://www.ncbi.nlm.nih.gov/pubmed/27021825/ doi: 10.1016/j.cytogfr.2016.03.003 id: cord-004400-li1sc47z author: Ma, Jingjiao title: Acetylation at K108 of the NS1 protein is important for the replication and virulence of influenza virus date: 2020-02-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Non-structural protein 1 (NS1) of influenza virus is a multifunctional protein that plays an important role in virus replication and virulence. In this study, an acetylation modification was identified at the K108 residue of the NS1 protein of H1N1 influenza virus. To further explore the function of the K108 acetylation modification of the NS1 protein, a deacetylation-mimic mutation (K108R) and a constant acetylation-mimic mutation (K108Q) were introduced into the NS1 protein in the background of A/WSN/1933 H1N1 (WSN), resulting in two mutant viruses (WSN-NS1-108R and WSN-NS1-108Q). In vitro and mouse studies showed that the deacetylation-mimic mutation K108R in the NS1 protein attenuated the replication and virulence of WSN-NS1-108R, while the constant acetylation-mimic mutant virus WSN-NS1-108Q showed similar replication and pathogenicity as the wild-type WSN virus (WSN-wt). The results indicated that acetylation at K108 of the NS1 protein has an important role in the replication and virulence of influenza virus. To further explore the potential mechanism, the type I interferon (IFN-I) antagonistic activity of the three NS1 proteins (NS1-108Q, NS1-108R, and NS1-wt) was compared in cells, which showed that the K108R mutation significantly attenuated the IFN-β antagonistic activity of the NS1 protein compared with NS1-wt and NS1-108Q. Both NS1-wt and NS1-108Q inhibited the IFN-β response activated by RIG-I CARD domain, MAVS, TBK1, and IRF3 more efficiently than the NS1-108R protein in cells. Taken together, the results indicated that acetylation at NS1 K108 is important for the IFN antagonistic activity of the NS1 protein and virulence of the influenza virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038556/ doi: 10.1186/s13567-020-00747-3 id: cord-002079-jne14jqf author: MacParland, Sonya A. title: Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date: 2016-05-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Inflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread. Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV). Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. Liver inflammation was induced in vivo using a murine model of hepatic ischemia/reperfusion injury. Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication. These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states. IMPORTANCE Inflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread. Blunted immunity as a result of inappropriate innate inflammatory responses is a common characteristic of chronic viral infections. Previous studies have shown that expression of certain interferon-stimulated genes is upregulated in chronic HCV infection, leading to impaired hepatocyte responses. In this study, we show that multiple inflammatory stimuli can modulate interferon stimulated gene expression and thus inhibit hepatocyte interferon signaling via USP18 induction. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with the induction of USP18 representing a potential target for intervention in various inflammatory states. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886784/ doi: 10.1128/jvi.02557-15 id: cord-016499-5iqpl23p author: Mackay, Ian M. title: Rhinoviruses date: 2014-02-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Picornaviruses, which include the human rhinoviruses (HRVs) and enteroviruses (EVs), are the most frequent cause of acute human illness worldwide. HRVs are the most prevalent cause of acute respiratory tract illnesses (ARIs) which usually commence in the upper respiratory tract (URT). ARIs are the leading cause of morbidity in children under 5 years and occur in all seasons. ARIs linked to HRV infections are associated with excessive and perhaps inappropriate antibiotic prescribing and with significant direct and indirect healthcare expenditure. ARI incidence is highest in the first 2 years of life, with up to thirteen episodes per year including up to six positive for an HRV, and it is not uncommon to average one infection per child-month. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120790/ doi: 10.1007/978-1-4899-7448-8_29 id: cord-310444-02dsqbeg author: Mahlakoiv, T. title: P136 Combined action of type I and type III IFN restricts initial replication of SARS-coronavirus in the lung but fails to inhibit systemic virus spread date: 2012-09-30 words: 2273.0 sentences: 127.0 pages: flesch: 47.0 cache: ./cache/cord-310444-02dsqbeg.txt txt: ./txt/cord-310444-02dsqbeg.txt summary: Conclusion Our data suggest that the failure of STAT1-deficient mice to efficiently control initial SARS-CoV replication in the lung is due to impaired type I and type III IFN signaling, whereas the failure to control subsequent systemic viral spread is due to unrelated defects in STAT1-deficient mice. The type III interferons are especially important in pulmonary infection, produced in response to viral infection and bacterial PAMPs. IFN-k is activated by and induces NF-jB signaling and promotes expression of Th1 cytokines. Consistent with the expected participation of IFN-k in NF-jB signaling, we measured decreased expression of KC, TNF and GM-CSF and increased IL-10 in the IL-28RÀ/ -BAL (P < 0.05), although there were no significant differences in the populations of immune cells (neutrophils, DC, macrophages) recruited to the airways of the wild type or IL-28RÀ/À mice. Ligation of immunoreceptor tyrosine-based activation motif (ITAM)associated receptors in macrophages can initiate potent induction of negative regulators, including anti-inflammatory cytokine IL-10, signaling inhibitors SOCS3, ABIN3, A20 and transcriptional repressor Hes1 [1] . abstract: Introduction STAT1-deficient mice are more susceptible to infection with SARS-Coronavirus (SARS-CoV) than type I IFN receptor-deficient mice. The increased susceptibility of STAT1-deficient mice is potentially due to the lack of functional type III IFN (IFN-λ) signalling. Methods We used mice lacking functional receptors for both type I and type III IFN (dKO) to evaluate the possibility that type III IFN plays a decisive role in SARS-CoV protection. Results We found that viral peak titres in lungs of dKO and STAT1-deficient mice were similar, although significantly higher than in wild-type mice. The kinetics of viral clearance from the lung was also comparable in dKO and STAT1-deficient mice. Surprisingly, however, infected dKO mice remained healthy, whereas infected STAT1-deficient mice developed liver pathology and eventually succumbed to neurological disease. Conclusion Our data suggest that the failure of STAT1-deficient mice to efficiently control initial SARS-CoV replication in the lung is due to impaired type I and type III IFN signaling, whereas the failure to control subsequent systemic viral spread is due to unrelated defects in STAT1-deficient mice. url: https://www.sciencedirect.com/science/article/pii/S1043466612004735 doi: 10.1016/j.cyto.2012.06.228 id: cord-308298-5ntdb8yf author: Mair, Kerstin H title: Porcine CD8α(dim/-)NKp46(high) NK cells are in a highly activated state date: 2013-03-01 words: 7630.0 sentences: 429.0 pages: flesch: 56.0 cache: ./cache/cord-308298-5ntdb8yf.txt txt: ./txt/cord-308298-5ntdb8yf.txt summary: Functional analyses revealed that splenic NKp46(high) NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Splenic NKp46 high NK cells showed a significantly reduced level of CD8α expression compared to the other splenic NK-cell subsets in all animals analysed Sequences of primers (5''-3'') for target genes as well as primer positions on (+) strand, length of specific product in base pairs (bp) and product melting temperature in°C are indicated. Splenic NKp46 high NK cells showed an overall higher expression of this receptor compared to NKp46and NKp46 + NK-cell subsets from both spleen and blood. Splenic NKp46 high NK cells showed highly elevated expression of this activating receptor compared to the other two NKp46-defined subsets in spleen as well as in blood in all animals analysed, which could be demonstrated on protein as well as on mRNA level. abstract: Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46(-) and NKp46(+) cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46(high) phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α(+)NKp46(-) and NKp46(+) NK-cell subsets in spleen and blood. Additionally NKp46(high) NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46(high) NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46(high) NK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46(high) NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ. url: https://www.ncbi.nlm.nih.gov/pubmed/23452562/ doi: 10.1186/1297-9716-44-13 id: cord-312001-8p7scli8 author: Majzoub, Karim title: The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans date: 2019-08-16 words: 10056.0 sentences: 548.0 pages: flesch: 46.0 cache: ./cache/cord-312001-8p7scli8.txt txt: ./txt/cord-312001-8p7scli8.txt summary: Consequently, animal cells have evolved devoted pathways which (1) sense and recognize pathogen-associated molecular patterns (PAMPs) and, more particularly, virus-associated molecular signatures; (2) initiate signaling cascades stemming from the site of detection, translocating the information to the nucleus; and (3) induce a transcriptional program that confers an antiviral state to the host ( Figure 1 ). While the cytosolic recognition of viral RNA is almost exclusively mediated by RLRs, several proteins have been proposed to play a role in DNA sensing and triggering innate immune responses, such as the DNA-dependent activator of IFN-regulatory factors (DAI), DDX41, RNA polymerase III, IFI16 and DNA-PK [62] [63] [64] [65] [66] [67] . Although the pathway leading to the transcriptional activation of Vago is still poorly understood in insects, these studies established that DExD/H-box helicase containing proteins, like Dicer and RLRs, may represent an evolutionarily conserved set of viral nucleic acid sensors that direct antiviral responses in animals [159] . abstract: Animal cells have evolved dedicated molecular systems for sensing and delivering a coordinated response to viral threats. Our understanding of these pathways is almost entirely defined by studies in humans or model organisms like mice, fruit flies and worms. However, new genomic and functional data from organisms such as sponges, anemones and mollusks are helping redefine our understanding of these immune systems and their evolution. In this review, we will discuss our current knowledge of the innate immune pathways involved in sensing, signaling and inducing genes to counter viral infections in vertebrate animals. We will then focus on some central conserved players of this response including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and cGAS-STING, attempting to put their evolution into perspective. To conclude, we will reflect on the arms race that exists between viruses and their animal hosts, illustrated by the dynamic evolution and diversification of innate immune pathways. These concepts are not only important to understand virus-host interactions in general but may also be relevant for the development of novel curative approaches against human disease. url: https://doi.org/10.3390/v11080758 doi: 10.3390/v11080758 id: cord-333650-4towah1t author: Malmo, Jostein title: Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis date: 2016-05-12 words: 4659.0 sentences: 250.0 pages: flesch: 50.0 cache: ./cache/cord-333650-4towah1t.txt txt: ./txt/cord-333650-4towah1t.txt summary: Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. To determine the presence of antiviral cytokines in children infected with hMPV and controls, we initially investigated the expression of type I, II and III IFNs. Fig 1A shows that only A2 infected children had slightly elevated mRNA levels of the type I IFN-β compared to the controls. Fig 2 shows the mRNA expression of A) IκBα, a repressor gene induced by NF-κB activation [19] , B) IL-1β, C) IL-18 and D) NLRP3 in hMPV infected children and controls. A previous study comparing the expression of several inflammatory cytokines in hMPV, RSV and influenza virus, detected elevated levels of TNF-α, IL-6 and IL-1β protein in nasal washes from infants with RTI [9] . abstract: Human metapneumovirus (hMPV) causes severe airway infection in children that may be caused by an unfavorable immune response. The nature of the innate immune response to hMPV in naturally occurring infections in children is largely undescribed, and it is unknown if inflammasome activation is implicated in disease pathogenesis. We examined nasopharynx aspirates and blood samples from hMPV-infected children without detectable co-infections. The expression of inflammatory and antiviral genes were measured in nasal airway secretions by relative mRNA quantification while blood plasma proteins were determined by a multiplex immunoassay. Several genes were significantly up-regulated at mRNA and protein level in the hMPV infected children. Most apparent was the expression of the chemokine IP-10, the pro-inflammatory cytokine IL-18 in addition to the interferon inducible gene ISG54. Interestingly, children experiencing more severe disease, as indicated by a severity index, had significantly more often up-regulation of the inflammasome-associated genes IL-1β and NLRP3. Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. Our study is the first to demonstrate that inflammasome components are associated with increased illness severity in hMPV-infected children. url: https://doi.org/10.1371/journal.pone.0155484 doi: 10.1371/journal.pone.0155484 id: cord-297790-tpjxt0w5 author: Mandl, Judith N. title: Going to Bat(s) for Studies of Disease Tolerance date: 2018-09-20 words: 9486.0 sentences: 393.0 pages: flesch: 40.0 cache: ./cache/cord-297790-tpjxt0w5.txt txt: ./txt/cord-297790-tpjxt0w5.txt summary: Among them are filoviruses (e.g., Marburg, Ebola), coronaviruses (e.g., SARS, MERS), henipaviruses (e.g., Hendra, Nipah) which share the common features that they are all RNA viruses, and that a dysregulated immune response is an important contributor to the tissue damage and hence pathogenicity that results from infection in humans. It is likely that differences in evolutionary history of pathogen exposure between bats and humans have led to distinct adaptations in anti-viral immune responses and the ability to tolerate certain infections without disease while being susceptible to others. We summarize this work below, but comparisons of observations made across species suggest that although a number of species appear to be capable of avoiding the pathological effects of RNA virus infection, each bat species may have achieved this through distinct pathways, possibly involving changes to both increase pathogen replication control and to mitigate any immunopathology through decreased inflammatory responses and hence increased disease tolerance. abstract: A majority of viruses that have caused recent epidemics with high lethality rates in people, are zoonoses originating from wildlife. Among them are filoviruses (e.g., Marburg, Ebola), coronaviruses (e.g., SARS, MERS), henipaviruses (e.g., Hendra, Nipah) which share the common features that they are all RNA viruses, and that a dysregulated immune response is an important contributor to the tissue damage and hence pathogenicity that results from infection in humans. Intriguingly, these viruses also all originate from bat reservoirs. Bats have been shown to have a greater mean viral richness than predicted by their phylogenetic distance from humans, their geographic range, or their presence in urban areas, suggesting other traits must explain why bats harbor a greater number of zoonotic viruses than other mammals. Bats are highly unusual among mammals in other ways as well. Not only are they the only mammals capable of powered flight, they have extraordinarily long life spans, with little detectable increases in mortality or senescence until high ages. Their physiology likely impacted their history of pathogen exposure and necessitated adaptations that may have also affected immune signaling pathways. Do our life history traits make us susceptible to generating damaging immune responses to RNA viruses or does the physiology of bats make them particularly tolerant or resistant? Understanding what immune mechanisms enable bats to coexist with RNA viruses may provide critical fundamental insights into how to achieve greater resilience in humans. url: https://doi.org/10.3389/fimmu.2018.02112 doi: 10.3389/fimmu.2018.02112 id: cord-263200-ntq1f4ix author: Mao, He-Ting title: HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex date: 2016-05-21 words: 4451.0 sentences: 320.0 pages: flesch: 54.0 cache: ./cache/cord-263200-ntq1f4ix.txt txt: ./txt/cord-263200-ntq1f4ix.txt summary: To initiate an effective antiviral response, RNA viruses are recognized by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs), and then trigger multiple signaling pathways to promote the production of proinflammatory cytokines, including type I IFNs [1] [2] [3] [4] . In this study, we demonstrate for the first time that HACE1 contributes to negative regulation of the virus-induced type I IFN signaling via disrupting the MAVS-TRAF3 complex. HACE1 suppressed virus-induced type I IFN signaling independently of its ubiquitin E3 ligase activity. By a small-scale screening of unknown ubiquitin E3 ligases in the regulation of virus-induced type I IFN signaling by the dual-luciferase reporter, we identified HACE1 as a potential negative regulator in this pathway. By a small-scale screening of unknown ubiquitin E3 ligases in the regulation of virus-induced type I IFN signaling by the dual-luciferase reporter, we identified HACE1 as a potential negative regulator in this pathway. abstract: During virus infection, the cascade signaling pathway that leads to the production of proinflammatory cytokines is controlled at multiple levels to avoid detrimental overreaction. HACE1 has been characterized as an important tumor suppressor. Here, we identified HACE1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of HACE1 inhibited Sendai virus- or poly (I:C)-induced signaling and resulted in reduced IFNB1 production and enhanced virus replication. Knockdown of HACE1 expression exhibited the opposite effects. Ubiquitin E3 ligase activity of the dead mutant HACE1/C876A had a comparable inhibitory function as WT HACE1, suggesting that the suppressive function of HACE1 on virus-induced signaling is independent of its E3 ligase activity. Further study indicated that HACE1 acted downstream of MAVS and upstream of TBK1. Mechanistic studies showed that HACE1 exerts its inhibitory role on virus-induced signaling by disrupting the MAVS-TRAF3 complex. Therefore, we uncovered a novel function of HACE1 in innate immunity regulation. url: https://www.ncbi.nlm.nih.gov/pubmed/27213432/ doi: 10.3390/v8050146 id: cord-002844-jv42o789 author: Marcos-Villar, Laura title: Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response date: 2018-01-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications. Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection. DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection. A particular increase in H3K79 methylation was observed and the use of an inhibitor of the specific H3K79 methylase, Dot1L enzyme, or its silencing, increased influenza virus replication. The antiviral response was reduced in conditions of Dot1L downregulation, since decreased nuclear translocation of NF-kB complex, and IFN-β, Mx1 and ISG56 expression was detected. The data suggested a control of antiviral signaling by methylation of H3K79 and consequently, influenza virus replication was unaffected in IFN pathway-compromised, Dot1L-inhibited cells. H3K79 methylation also controlled replication of another potent interferon-inducing virus such as vesicular stomatitis virus, but did not modify amplification of respiratory syncytial virus that poorly induces interferon signaling. Epigenetic methylation of H3K79 might have an important role in controlling interferon-induced signaling against viral pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775356/ doi: 10.1038/s41598-018-19370-6 id: cord-320663-xypg6evo author: Market, Marisa title: Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies date: 2020-06-23 words: 14038.0 sentences: 659.0 pages: flesch: 42.0 cache: ./cache/cord-320663-xypg6evo.txt txt: ./txt/cord-320663-xypg6evo.txt summary: A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. Natural Killer (NK) cells are a key component of the innate immune system and are critical in the response to many viral infections in humans and animal models (1) (2) (3) . Altogether these studies show that during acute CoV infection, inflammatory monocyte-macrophages and neutrophils accumulate in the lungs and produce cytokines and chemokines that induce the activation and migration of lymphocytes, including NK cells, to the lungs, where they could be one of the main producers of IFN-γ (148). Studies have reported that patients infected with SARS-CoV-2 have lower levels of circulating NK cells and these express a greater level of inhibitory receptors (e.g., NKG2A) while producing less IFN-γ (127, 129, 130) . abstract: Natural Killer (NK) cells are innate immune responders critical for viral clearance and immunomodulation. Despite their vital role in viral infection, the contribution of NK cells in fighting SARS-CoV-2 has not yet been directly investigated. Insights into pathophysiology and therapeutic opportunities can therefore be inferred from studies assessing NK cell phenotype and function during SARS, MERS, and COVID-19. These studies suggest a reduction in circulating NK cell numbers and/or an exhausted phenotype following infection and hint toward the dampening of NK cell responses by coronaviruses. Reduced circulating NK cell levels and exhaustion may be directly responsible for the progression and severity of COVID-19. Conversely, in light of data linking inflammation with coronavirus disease severity, it is necessary to examine NK cell potential in mediating immunopathology. A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. In this review, we summarize the current understanding of how NK cells respond in both early and late coronavirus infections, and the implication for ongoing COVID-19 clinical trials. Using this immunological lens, we outline recommendations for therapeutic strategies against COVID-19 in clearing the virus while preventing the harm of immunopathological responses. url: https://doi.org/10.3389/fimmu.2020.01512 doi: 10.3389/fimmu.2020.01512 id: cord-337458-dc90ecfe author: Markwalter, Christine F. title: Inorganic Complexes and Metal-Based Nanomaterials for Infectious Disease Diagnostics date: 2018-12-04 words: 40568.0 sentences: 2391.0 pages: flesch: 40.0 cache: ./cache/cord-337458-dc90ecfe.txt txt: ./txt/cord-337458-dc90ecfe.txt summary: In this review, we define the components of a diagnostic to include: (1) the target biomarker, an endogenous indicator of a disease state, which is most often a pathogen or host protein, carbohydrate, or nucleic acid sequence, (2) sample preparation, which allows for biomarker isolation, purification, and/or concentration from complex biological matrices, (3) molecular recognition elements, which specifically capture and detect the target biomarker, (4) signal generation and amplification, and (5) instrumentation for signal read-out. 113, 114 In subsequent studies, the group developed and optimized a hand-held, easy-to-use device 85, 115 (Figure 8A ) in which HRP2-bound, IMAC-functionalized magnetic beads were directly transferred to the sample pad of commercial malaria lateral flow assays. If combined with one of the sample preparation strategies discussed previously (section 3) or integrated with paper or another field-ready substrate, this Ir(III)-based detection strategy could produce a robust and sensitive assay that is applicable in low-resource diagnostic settings. abstract: [Image: see text] Infectious diseases claim millions of lives each year. Robust and accurate diagnostics are essential tools for identifying those who are at risk and in need of treatment in low-resource settings. Inorganic complexes and metal-based nanomaterials continue to drive the development of diagnostic platforms and strategies that enable infectious disease detection in low-resource settings. In this review, we highlight works from the past 20 years in which inorganic chemistry and nanotechnology were implemented in each of the core components that make up a diagnostic test. First, we present how inorganic biomarkers and their properties are leveraged for infectious disease detection. In the following section, we detail metal-based technologies that have been employed for sample preparation and biomarker isolation from sample matrices. We then describe how inorganic- and nanomaterial-based probes have been utilized in point-of-care diagnostics for signal generation. The following section discusses instrumentation for signal readout in resource-limited settings. Next, we highlight the detection of nucleic acids at the point of care as an emerging application of inorganic chemistry. Lastly, we consider the challenges that remain for translation of the aforementioned diagnostic platforms to low-resource settings. url: https://doi.org/10.1021/acs.chemrev.8b00136 doi: 10.1021/acs.chemrev.8b00136 id: cord-252568-b8sbvy0g author: Marques Neto, Lázaro Moreira title: Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development date: 2017-03-08 words: 5317.0 sentences: 260.0 pages: flesch: 39.0 cache: ./cache/cord-252568-b8sbvy0g.txt txt: ./txt/cord-252568-b8sbvy0g.txt summary: There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. However, many NPs have been shown to stimulate immune responses, including cell recruitment, activation of antigen (Ag)-presenting cells (APCs), and induction of cytokine and chemokine release. Among the vaccines targeting extracellular bacteria and toxin, two were formulated with lipopolysaccharide (LPS) in glycopeptide Ag. The use of glycoantigen and LPS can trigger an intense response through TLR4 and B cell receptor activation; the presence of gold NPs (AuNPs) may have minimal influence on this response. To understand the possible uses of MeNPs as platforms for vaccines against infectious diseases, analysis is needed of the impact of different physicochemical characteristics of NPs on the innate immune response (Figure 1) . abstract: Subunit vaccines are safer but less immunogenic than live-attenuated vaccines or whole cell inactivated vaccines. Adjuvants are used to enhance and modulate antigen (Ag) immunogenicity, aiming to induce a protective and long-lasting immune response. Several molecules and formulations have been studied for their adjuvanticity, but only seven have been approved to formulate human vaccines. Metallic nanoparticles (MeNPs), particularly those containing gold and iron oxides, are widely used in medicine for diagnosis and therapy and have been used as carriers for drugs and vaccines. However, little is known about the immune response elicited by MeNPs or about their importance in the development of new vaccines. There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. This review focuses on the characteristics of MeNPs that could facilitate the induction of a cellular immune response, particularly T-helper 1 and T-helper 17, and their potential functions as adjuvants for subunit vaccines. url: https://www.ncbi.nlm.nih.gov/pubmed/28337198/ doi: 10.3389/fimmu.2017.00239 id: cord-005595-vzkcin1l author: Massa, P. T. title: Viral particles induce Ia antigen expression on astrocytes date: 1986 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094962/ doi: 10.1038/320543a0 id: cord-313957-hviv5zar author: Masucci, Maria Grazia title: Viral Ubiquitin and Ubiquitin-Like Deconjugases—Swiss Army Knives for Infection date: 2020-08-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Posttranslational modifications of cellular proteins by covalent conjugation of ubiquitin and ubiquitin-like polypeptides regulate numerous cellular processes that are captured by viruses to promote infection, replication, and spreading. The importance of these protein modifications for the viral life cycle is underscored by the discovery that many viruses encode deconjugases that reverse their functions. The structural and functional characterization of these viral enzymes and the identification of their viral and cellular substrates is providing valuable insights into the biology of viral infections and the host’s antiviral defense. Given the growing body of evidence demonstrating their key contribution to pathogenesis, the viral deconjugases are now recognized as attractive targets for the design of novel antiviral therapeutics. url: https://doi.org/10.3390/biom10081137 doi: 10.3390/biom10081137 id: cord-319248-ynoxec7k author: Matsuyama, Toshifumi title: An aberrant STAT pathway is central to COVID-19 date: 2020-10-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: COVID-19 is caused by SARS-CoV-2 infection and characterized by diverse clinical symptoms. Type I interferon (IFN-I) production is impaired and severe cases lead to ARDS and widespread coagulopathy. We propose that COVID-19 pathophysiology is initiated by SARS-CoV-2 gene products, the NSP1 and ORF6 proteins, leading to a catastrophic cascade of failures. These viral components induce signal transducer and activator of transcription 1 (STAT1) dysfunction and compensatory hyperactivation of STAT3. In SARS-CoV-2-infected cells, a positive feedback loop established between STAT3 and plasminogen activator inhibitor-1 (PAI-1) may lead to an escalating cycle of activation in common with the interdependent signaling networks affected in COVID-19. Specifically, PAI-1 upregulation leads to coagulopathy characterized by intravascular thrombi. Overproduced PAI-1 binds to TLR4 on macrophages, inducing the secretion of proinflammatory cytokines and chemokines. The recruitment and subsequent activation of innate immune cells within an infected lung drives the destruction of lung architecture, which leads to the infection of regional endothelial cells and produces a hypoxic environment that further stimulates PAI-1 production. Acute lung injury also activates EGFR and leads to the phosphorylation of STAT3. COVID-19 patients’ autopsies frequently exhibit diffuse alveolar damage (DAD) and increased hyaluronan (HA) production which also leads to higher levels of PAI-1. COVID-19 risk factors are consistent with this scenario, as PAI-1 levels are increased in hypertension, obesity, diabetes, cardiovascular diseases, and old age. We discuss the possibility of using various approved drugs, or drugs currently in clinical development, to treat COVID-19. This perspective suggests to enhance STAT1 activity and/or inhibit STAT3 functions for COVID-19 treatment. This might derail the escalating STAT3/PAI-1 cycle central to COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/33037393/ doi: 10.1038/s41418-020-00633-7 id: cord-253743-hj9mq6lq author: Matthew, J. title: Seasonal Distribution Of Respiratory Viruses In Pediatric Asthma In Trinidad West Indies date: 2007-01-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0091674906029514 doi: 10.1016/j.jaci.2006.11.509 id: cord-007664-c5snhymz author: Mauerhoff, Thekla title: Differential expression and regulation of major histocompatibility complex (MHC) products in neural and glial cells of the human fetal brain date: 2002-11-13 words: 4673.0 sentences: 212.0 pages: flesch: 51.0 cache: ./cache/cord-007664-c5snhymz.txt txt: ./txt/cord-007664-c5snhymz.txt summary: To gain an insight into the regulation of HLA in the different cell types in the CNS and to compare it to that observed in the endocrine organs, we have studied the effect of the lympho/monokines interferon (IFN)-α and -γ, tumour necrosis factor (TNF)-α, and interleukin (IL)-2 and other agents on this aspect of the biology of human fetal brain cells in culture. It has previously been reported that primary cultures of human fetal brain tissue can be a useful substrate for studying the expression of cell type-specific antigens, e.g. gangliosides, tetanus toxin receptors (Dickson et al., 1982 (Dickson et al., , 1985 , and the present data confirm that they can also be successfully employed to investigate the expression and modulation of HLA molecules. abstract: The cells of the central nervous system (CNS) have the peculiarity of physiologically expressing very low levels of HLA molecules. In multiple sclerosis (MS), however, as in endocrine autoimmune diseases, there is a marked increase of HLA expression in the tissue (i.e. the plaques) and this is attributable not only to infiltrating cells but also to the astrocytes. To gain an insight into the regulation of HLA in the different cell types in the CNS and to compare it to that observed in the endocrine organs, we have studied the effect of the lympho/monokines interferon (IFN)-α and -γ, tumour necrosis factor (TNF)-α, and interleukin (IL)-2 and other agents on this aspect of the biology of human fetal brain cells in culture. A two-colour immunofluorescence technique which combines antibodies to diverse CNS cell markers and monoclonal antibodies (MoAbs) to the non-polymorphic region of HLA molecules was used throughout this study. In control cultures, only astrocytes expressed MHC class I, but after incubation with either IFN-γ or TNF-α oligodendrocytes acquired class I expression. Surprisingly, astrocytes became spontaneously class II positive in culture and this was greatly enhanced by IFN-γ. Other agents such as IL-2, epidermal growth factor, phorbolmyristate acetate and lectins had no effect. The expression of HLA molecules in the cells of the CNS both in basal conditions and in response to lymphokines is therefore selective and highly heterogenous, thus reflecting their intrinsic biological diversity. These findings may help to explain the features of the immunopathology of MS and also of latent viral infections of neural cells. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119889/ doi: 10.1016/0165-5728(88)90049-5 id: cord-282395-uwxk1o6d author: Mayer, Karin title: Fatal outcome of human coronavirus NL63 infection despite successful viral elimination by IFN‐alpha in a patient with newly diagnosed ALL date: 2016-03-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: INTRODUCTION: Human coronavirus NL63 (HCoV‐NL63) is one of four common human respiratory coronaviruses. Despite high incidence, HCoV infections are grossly understudied. We here report a case of HCoV infection in a leukemia patient with fatal ARDS despite successful virus elimination by pegylated interferon‐alpha (PEG‐IFN‐α). CASE: The 27‐year‐old female pre‐T‐ALL patient was treated according to the German‐Multicenter Trial for Adult ALL protocol. No relevant infectious complications were seen until day 35 when the neutropenic patient developed fever without any clinical focus. Antibiotic prophylaxis was switched to meropenem. The patient deteriorated rapidly with respiratory failure due to ARDS. Anti‐infectious therapy was escalated to additional linezolid and liposomal amphotericine‐B. BAL revealed a significant viral load of HCoV‐NL63. Based on successful application of PEG‐IFN against the related SARS coronavirus in animal experiments, a single injection of 180 μg PEG‐IFN‐α2b was applied. Despite immediate initiation of treatment and elimination of virus in subsequent tests, the progressive lung failure led to death 7 d after onset of fever with massive lung bleeding as a consequence of diffuse alveolar hemorrhage. CONCLUSION: This report emphasizes the fatal consequences of common respiratory virus infections in immunocompromised patients. HCoV‐NL63 replication can be reduced by treatment with peg‐IFN if diagnosed early. url: https://doi.org/10.1111/ejh.12744 doi: 10.1111/ejh.12744 id: cord-334134-fhie2m3u author: Mazaleuskaya, Liudmila title: Protective Role of Toll-like Receptor 3-Induced Type I Interferon in Murine Coronavirus Infection of Macrophages date: 2012-05-24 words: 7171.0 sentences: 496.0 pages: flesch: 59.0 cache: ./cache/cord-334134-fhie2m3u.txt txt: ./txt/cord-334134-fhie2m3u.txt summary: We assessed the effect of triggering TLR2, TLR3, TLR4, and TLR7 with selected ligands on the susceptibility of the J774A.1 macrophage cell line to infection with murine coronavirus (mouse hepatitis virus, [MHV]). These results together with the antiviral effect of poly I:C (Figure 3 ) suggested that the protective role of TLR3 against coronavirus infection in J774A.1 macrophages may be mediated by type I IFN. We hypothesized that the differential effect of TLR ligands on MHV production is due to their variable ability to induce type I IFN crucial for triggering an "antiviral state" and protecting cells from virus infection [26, 38] . In the present study prestimulation of J774A.1 macrophages with poly I:C, a potent type I IFN inducer, resulted in a strong IFN-β response that triggered antiviral immunity and protected macrophages from MHV infection before and after virus adsorption. abstract: Toll-like Receptors (TLRs) sense viral infections and induce production of type I interferons (IFNs), other cytokines, and chemokines. Viral recognition by TLRs and other pattern recognition receptors (PRRs) has been proven to be cell-type specific. Triggering of TLRs with selected ligands can be beneficial against some viral infections. Macrophages are antigen-presenting cells that express TLRs and have a key role in the innate and adaptive immunity against viruses. Coronaviruses (CoVs) are single-stranded, positive-sense RNA viruses that cause acute and chronic infections and can productively infect macrophages. Investigation of the interplay between CoVs and PRRs is in its infancy. We assessed the effect of triggering TLR2, TLR3, TLR4, and TLR7 with selected ligands on the susceptibility of the J774A.1 macrophage cell line to infection with murine coronavirus (mouse hepatitis virus, [MHV]). Stimulation of TLR2, TLR4, or TLR7 did not affect MHV production. In contrast, pre-stimulation of TLR3 with polyinosinic-polycytidylic acid (poly I:C) hindered MHV infection through induction of IFN-β in macrophages. We demonstrate that activation of TLR3 with the synthetic ligand poly I:C mediates antiviral immunity that diminishes (MHV-A59) or suppresses (MHV-JHM, MHV-3) virus production in macrophages. url: https://doi.org/10.3390/v4050901 doi: 10.3390/v4050901 id: cord-000104-3b8b8p61 author: McWhirter, Sarah M. title: A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP date: 2009-08-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di–guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid–sensing pathways. Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737161/ doi: 10.1084/jem.20082874 id: cord-022226-qxp0gfp3 author: Meager, Anthony title: Interferons Alpha, Beta, and Omega date: 2007-09-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Interferon alpha (IFN-α) is a mixture of closely related proteins, termed “subtypes,” expressed from distinct chromosomal genes. Interferon β (IFN-β) is a single protein species and is molecularly related to IFN-α subtypes, although it is antigenically distinct from them. IFN omega (IFN-ω) is antigenically distinct from IFN-α and IFN-β but is molecularly related to both. The genes of three IFN subtypes are tandemly arranged on the short arm of chromosome 9. They are transiently expressed following induction by various exogenous stimuli, including viruses. They are synthesized from their respective mRNAs for relatively short periods following gene activation and are secreted to act, via specific cell surface receptors, on other cells. IFN-α subtypes are secreted proteins and as such are transcribed from mRNAs as precursor proteins, pre-IFN-α, containing N-terminal signal polypeptides of 23 hydrophobic amino acids (aa) mainly. Pre-IFN-β contains 187 aa, of which 21 comprise the N-terminal signal polypeptide and 166 comprise the mature IFN-β protein. IFN-ω contains 195 aa—the N-terminal 23 comprising the signal sequence and the remaining 172, the mature IFN-ω protein. At the C-terminus, the aa sequence of IFN-ω is six residues longer than that of IFN-α or IFN-β proteins. IFN-α, as a mixture of subtypes, and IFN-ω may be produced together following viral infection of null lymphocytes or monocytes/macrophages. The biological activities of IFNs are mostly dependent upon protein synthesis with selective subsets of proteins mediating individual activities. IFNs can also stimulate indirect antiviral and antitumor mechanisms, depending upon cellular differentiation and the induction of cytotoxic activity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155463/ doi: 10.1016/b978-012498340-3/50026-9 id: cord-355671-t890eixt author: Medina, Gisselle N. title: Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo date: 2020-06-16 words: 6363.0 sentences: 346.0 pages: flesch: 46.0 cache: ./cache/cord-355671-t890eixt.txt txt: ./txt/cord-355671-t890eixt.txt summary: FMDV Lpro is a papain-like protease (PLP) known to block the cellular innate immune response, at both the transcriptional and translational level by utilizing different mechanisms, including (i) shutting down translation of host capped mRNAs through the cleavage of the translation initiation factor eIF4G (5, 6); (ii) downregulating IFN mRNA expression by causing degradation of NF-B, IRF-3, IRF-7, and LGP2 (7-10); (iii) targeting the chromatin remodeling machinery to disrupt the expression of IFN and ISG mRNAs (11) ; and (iv) targeting of G3BP1/2 to block stress granule formation (12) . Importantly, engineering of an infectious clone carrying this mutation (LproW105A) rendered a viable FMDV with a perceptible level of attenuation and reduced deISGylation and DUB activity compared with wild-type (WT) virus during infection of porcine cells. To confirm these results using the FMDV host-specific ISGylation machinery during infection, we cloned the porcine ISG15 in a replicationdefective human adenovirus type 5 (Ad5) vector (Fig. 5B) and examined its antiviral activity in swine cells. abstract: Foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) affects several pathways of the host innate immune response. Previous studies in bovine cells demonstrated that deletions (leaderless [LLV]) or point mutations in Lpro result in increased expression of interferon (IFN) and IFN-stimulated genes (ISGs), including, among others, the ubiquitin-like protein modifier ISG15 and the ubiquitin specific peptidase USP18. In addition to its conventional papain-like protease activity, Lpro acts as a deubiquitinase (DUB) and deISGylase. In this study, we identified a conserved residue in Lpro that is involved in its interaction with ISG15. Mutation W105A rendered Escherichia coli-expressed Lpro unable to cleave the synthetic substrate pro-ISG15 while preserving cellular eIF4G cleavage. Interestingly, mutant FMDV W105A was viable. Overexpression of ISG15 and the ISGylation machinery in porcine cells resulted in moderate inhibition of FMDV replication, along with a decrease of the overall state of ISGylation in wild-type (WT)-infected cells. In contrast, reduced deISGylation was observed upon infection with W105A and leaderless virus. Reduction in the levels of deubiquitination was also observed in cells infected with the FMDV LproW105A mutant. Surprisingly, similarly to WT, infection with W105A inhibited IFN/ISG expression despite displaying an attenuated phenotype in vivo in mice. Altogether, our studies indicate that abolishing/reducing the deISGylase/DUB activity of Lpro causes viral attenuation independently of its ability to block the expression of IFN and ISG mRNA. Furthermore, our studies highlight the potential of ISG15 to be developed as a novel biotherapeutic molecule against FMD. IMPORTANCE In this study, we identified an aromatic hydrophobic residue in foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) (W105) that is involved in the interaction with ISG15. Mutation in Lpro W105 (A12-LproW105A) resulted in reduced deISGylation in vitro and in porcine-infected cells. Impaired deISGylase activity correlated with viral attenuation in vitro and in vivo and did not affect the ability of Lpro to block expression of type I interferon (IFN) and other IFN-stimulated genes. Moreover, overexpression of ISG15 resulted in the reduction of FMDV viral titers. Thus, our study highlights the potential use of Lpro mutants with modified deISGylase activity for development of live attenuated vaccine candidates, and ISG15 as a novel biotherapeutic against FMD. url: https://doi.org/10.1128/jvi.00341-20 doi: 10.1128/jvi.00341-20 id: cord-332154-2gej7h1d author: Meier, William A. title: Cytokines and synthetic double-stranded RNA augment the T helper 1 immune response of swine to porcine reproductive and respiratory syndrome virus date: 2004-12-08 words: 9170.0 sentences: 415.0 pages: flesch: 46.0 cache: ./cache/cord-332154-2gej7h1d.txt txt: ./txt/cord-332154-2gej7h1d.txt summary: Immunization of pigs with a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine initially elicits a weak interferon (IFN)-γ response. Based on the success of this intervention and the noted absence of IFN-a generation during PRRSV infection, the present studies were undertaken to determine if the antiviral adaptive immunity induced by vaccination with PRRS MLV could be modified simply by the co-administration of rIL-12 protein directly, or of either porcine IFN-a or IL-12 indirectly via plasmids expressing these cytokines. Although a similar response was evident during this time period for vaccinated pigs also i.m. injected with exogenous IL-12 either directly as protein or indirectly via IL-12 cDNA, immunized animals that were i.d. inoculated with IL-12 cDNA exhibited an overall 2.7-fold transient increase in the frequency of PRRSV-specific IFN-g SC at 2 weeks post-vaccination. Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) abstract: Immunization of pigs with a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine initially elicits a weak interferon (IFN)-γ response. To improve the immune response, an adjuvant consisting of plasmid encoding either porcine interleukin (IL)-12 or IFN-α was co-administered during vaccination. In the presence of either adjuvant, at least a three-fold increase in the primary virus-specific IFN-γ response was observed. While this enhancement was only transient (1 week) when the IL-12 expressing plasmid was used, the effect was not only still apparent at 6 weeks after vaccination in the presence of the IFN-α expressing plasmid but even after challenge with a virulent genetically divergent PRRSV. In contrast, no effect of either adjuvant on the production of anti-virus antibodies was noticed throughout the study. Despite the apparent augmentation of a T helper (Th) 1 type response by the inclusion of IFN-α or IL-12 during vaccination, this modulation did not necessarily correlate with a reduction in viremia. Since a similar increase in the degree of the IFN-γ response to the PRRSV vaccine could be achieved by substituting polyinosinic–polycytidylic acid in lieu of either cytokine, exposure to PRRSV in the presence of a variety of Th 1 polarizing molecules can positively influence the development of the cell-mediated immune response of swine to this pathogen. Conceivably, such intervention could be applied to improve the formulation of anti-PRRSV vaccines. url: https://api.elsevier.com/content/article/pii/S0165242704002636 doi: 10.1016/j.vetimm.2004.09.012 id: cord-023373-6wh1kb3p author: Melchjorsen, J. title: Differential Requirements for Toll‐Like Receptor Signalling for Induction of Chemokine Expression by Herpes Simplex Virus and Sendai Virus date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Toll‐like receptors (TLRs) are pattern recognition receptors of the innate immune system, which recognize molecular structures on pathogens or cellular stress‐associated molecules. TLR–ligand interactions trigger activation of inflammatory signal transduction and expression of genes involved in host defense. In this study, we have examined the requirement for different TLR adaptor molecules in virus‐induced chemokine expression and are currently trying to identify the TLR involved. We have found that both a herpesvirus [herpes simplex virus (HSV)] and a paramyxovirus (Sendai virus) require a functional genome to induce expression or proinflammatory chemokines in human and murine monocytic cell lines. For both viruses, this is independent of the TLR adaptor molecules TRIF and Mal. However, overexpression of the Vaccinia virus‐encoded inhibitor of TLR‐signalling A52R or dominant‐negative MyD88 totally inhibited HSV‐induced RANTES expression but only partially prevented Sendai virus from inducing this chemokine. This suggests that HSV‐induced RANTES expression occurs via a TLR pathways, whereas Sendai virus utilizes both TLR‐dependent and ‐independent pathways to stimulate expression of RANTES. We are currently trying to identify the TLRs involved. Data from these studies will also be presented at the meeting. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169484/ doi: 10.1111/j.0300-9475.2004.01423r.x id: cord-278648-hkvurb2k author: Menachery, Vineet D. title: Middle East Respiratory Syndrome Coronavirus Nonstructural Protein 16 Is Necessary for Interferon Resistance and Viral Pathogenesis date: 2017-11-15 words: 5195.0 sentences: 263.0 pages: flesch: 47.0 cache: ./cache/cord-278648-hkvurb2k.txt txt: ./txt/cord-278648-hkvurb2k.txt summary: While the absence of 2′O-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures and in vivo. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Generation of mutants with changes in the NSP16 KDKE active site resulted in IFN-mediated in vitro and in vivo attenuation of both mouse hepatitis virus (MHV) and SARS-CoV (9, 10) . While a more rapid CPE following both WT and dNSP16 mutant MERS-CoV infections precluded an equivalent finding at late time points, the SARS-CoV results suggest that the absence of NSP16 activity eventually initiates host response changes that contribute to attenuation at late time points. abstract: Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2′O-methyltransferase (2′O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis. While the absence of 2′O-MTase activity had only a marginal impact on propagation and replication in Vero cells, dNSP16 mutant MERS-CoV demonstrated significant attenuation relative to the control both in primary human airway cell cultures and in vivo. Further examination indicated that dNSP16 mutant MERS-CoV had a type I interferon (IFN)-based attenuation and was partially restored in the absence of molecules of IFN-induced proteins with tetratricopeptide repeats. Importantly, the robust attenuation permitted the use of dNSP16 mutant MERS-CoV as a live attenuated vaccine platform protecting from a challenge with a mouse-adapted MERS-CoV strain. These studies demonstrate the importance of the conserved 2′O-MTase activity for CoV pathogenesis and highlight NSP16 as a conserved universal target for rapid live attenuated vaccine design in an expanding CoV outbreak setting. IMPORTANCE Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′O-MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-CoV functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2′O-MTase function across CoVs. url: https://doi.org/10.1128/msphere.00346-17 doi: 10.1128/msphere.00346-17 id: cord-333600-k6ws97at author: Mihm, Sabine title: COVID-19: Possible Impact of the Genetic Background in IFNL Genes on Disease Outcomes date: 2020-04-28 words: 684.0 sentences: 42.0 pages: flesch: 48.0 cache: ./cache/cord-333600-k6ws97at.txt txt: ./txt/cord-333600-k6ws97at.txt summary: Host control of MHV infection is completely dependent on TLR7 triggering by viral RNA causing an immediate interferon (IFN) response [2] . Sex differences in TLR7 responses have been reported for humans -with female sex better coping with viral infection [4] [5] [6] -which is also a feature of COVID-19. Upon binding viral nucleic acid motifs, TLR7 induces the expression of type I IFNs (IFN-α and IFN-β) and the expression of the more recently described family of type III IFNs (IFN-λ [1] [2] [3] [4] . A common germ line genetic variation within the type III IFN gene locus has been most convincingly shown to determine the host''s capacity to cope with an infection induced by hepatitis C virus (HCV), an enveloped ssRNA virus of positive orientation, too, featuring tropism for liver epithelial cells. CD200 receptor controls sex-specific TLR7 responses to viral infection IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes abstract: nan url: https://doi.org/10.1159/000508076 doi: 10.1159/000508076 id: cord-278577-bx86tq0y author: Mikola, Emilia title: Tonsillar cytokine expression between patients with tonsillar hypertrophy and recurrent tonsillitis date: 2018-05-22 words: 3131.0 sentences: 186.0 pages: flesch: 43.0 cache: ./cache/cord-278577-bx86tq0y.txt txt: ./txt/cord-278577-bx86tq0y.txt summary: We investigated the differences in virus detection and T cell and interferon gene expression in patients undergoing tonsillectomy due to tonsillar hypertrophy or recurrent tonsillitis. However, data are scarce on the differences in tonsillar virus infections and immune responses between patients with tonsillar hypertrophy or recurrent tonsillitis [6] [7] [8] . Therefore, we studied whether virus detection and T cell and interferon gene expressions differed between the two main indications of surgery, tonsillar hypertrophy or recurrent tonsillitis. The adjustments for immunologic analyses were chosen using backward stepwise multivariable models that initially included clinical factors and virus infections which significantly differed between the groups (age, self-reported pollen allergy, self-smoking, both adenotomy and tonsillectomy performed, respiratory symptoms one month prior to the operation and bioavailable 25(OH)D level). This study shows differences in virus detections and T cell and interferon gene expressions in patients undergoing tonsillectomy due to tonsillar hypertrophy or recurrent tonsillitis. abstract: BACKGROUND: Tonsils provide an innovative in vivo model for investigating immune response to infections and allergens. However, data are scarce on the differences in tonsillar virus infections and immune responses between patients with tonsillar hypertrophy or recurrent tonsillitis. We investigated the differences in virus detection and T cell and interferon gene expression in patients undergoing tonsillectomy due to tonsillar hypertrophy or recurrent tonsillitis. METHODS: Tonsils of 89 surgical patients with tonsillar hypertrophy (n = 47) or recurrent tonsillitis (n = 42) were analysed. Patients were carefully characterized clinically. Standard questionnaire was used to asses preceding and allergy symptoms. Respiratory viruses were analysed in tonsils and nasopharynx by PCR. Quantitative real-time PCR was used to analyse intratonsillar gene expressions of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet. RESULTS: Median age of the subjects was 15 years (range 2–60). Patients with tonsillar hypertrophy were younger, smoked less often, had less pollen allergy and had more adenovirus, bocavirus-1, coronavirus and rhinovirus in nasopharynx (all P < 0.05). Only bocavirus-1 was more often detected in hypertrophic tonsils (P < 0.05). In age-adjusted analysis, tonsillar hypertrophy was associated with higher mRNA expressions of IL-37 (P < 0.05). CONCLUSIONS: Intratonsillar T cell and interferon gene expressions appeared to be relatively stable for both tonsillar hypertrophy and recurrent tonsillitis. Of the studied cytokines, only newly discovered anti-inflammatory cytokine IL-37, was independently associated with tonsillar hypertrophy showing slightly stronger anti-inflammatory response in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13601-018-0205-z) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/29942488/ doi: 10.1186/s13601-018-0205-z id: cord-319761-bu5pzbnv author: Miller, Craig S. title: Pleiotropic mechanisms of virus survival and persistence date: 2005-07-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viruses are enormously efficient infectious agents that have been implicated in causing human disease for centuries. Transmission of these pathogens continues to be from one life form to another in the form of isolated cases, epidemics, and pandemics. Each infection requires entry into a susceptible host, replication, and evasion of the immune system. Viruses are successful pathogens because they target specific cells for their attack, exploit the cellular machinery, and are efficient in circumventing and/or inhibiting key cellular events required of survival. This article reviews some of the advances that have taken place in human virology in the past 50 years, emphasizing mechanisms that contribute to, and are involved with, virus survival and persistence. url: https://api.elsevier.com/content/article/pii/S1079210405002374 doi: 10.1016/j.tripleo.2005.03.017 id: cord-299733-4mpz5l9e author: Mitchell, William M. title: Discordant Biological and Toxicological Species Responses to TLR3 Activation date: 2014-04-30 words: 6164.0 sentences: 343.0 pages: flesch: 45.0 cache: ./cache/cord-299733-4mpz5l9e.txt txt: ./txt/cord-299733-4mpz5l9e.txt summary: The mechanism of this differential response is consistent with a relative down-regulation of the NF-κB inflammatory cytokine induction pathway in the cynomolgus monkey and humans, but not observed systemically in rat. Primary protein sequences for the human (GenBank U88879); monkey species, including Macaca mulatta (Gen-Bank BAG55034.1 and AY864735), Macaca fasicularis ajp.amjpathol.org -The American Journal of Pathology (GenBank BAG55033.1), Papio anubis (XP_003899477), Callithrix jacchus (JAB01765.1), and Saimiri boliviensis (XP_003899477); and rodents, including the house mouse (GenBank AF355152/Mus musculus) and rat (GenBank AB116229/Rattus norvegicus), dog (GenBank XP_ 005630024/Canis lupus familiaris), and rabbit (GenBank ABB76310/Oryctolagus cuniculus) were aligned using Crystal W software version 10.1.2 provided by DNAStar (Madison, WI). The unexpected differential toxicities observed between the rat and a nonhuman primate prompted an examination of inflammatory cytokines (g-IFN, TNF-a, and IL-12p70) associated with infusion of a TLR3 agonist, rintatolimod. abstract: Toll-like receptors (TLRs) are highly conserved type 1 membrane proteins that initiate a multiplicity of transient gene transcriptions, resulting in innate and adaptive immune responses. These essential immune responses are triggered by common TLR pattern recognition receptors of microbial products expressed through the cytoplasmic carboxy-terminal Toll/IL-1 domain. Toll/IL-1 adapter protein cascades are induced by an activated Toll/IL-1 to induce transient transcription responses. All TLRs, with the exception of TLR3, use an MyD88 adapter to Toll/IL-1 to initiate a proinflammatory cascade. TLR3 uses the toll receptor 3/4 induction factor adapter to initiate a different cytosolic adapter cascade with double-stranded RNA agonists. This non-MyD88 pathway induces both NF-κB and type 1 interferon responses. By using a TLR3-restricted double-stranded RNA agonist, rintatolimod, we demonstrate significant unexpected differences in toxic responses between rats and primates. The mechanism of this differential response is consistent with a relative down-regulation of the NF-κB inflammatory cytokine induction pathway in the cynomolgus monkey and humans, but not observed systemically in rat. Our findings suggest evaluation of TLR3 agonists in drug therapy. url: https://www.ncbi.nlm.nih.gov/pubmed/24486326/ doi: 10.1016/j.ajpath.2013.12.006 id: cord-001397-nrq4ncdf author: Mlera, Luwanika title: The role of viral persistence in flavivirus biology date: 2014-05-12 words: 15593.0 sentences: 812.0 pages: flesch: 46.0 cache: ./cache/cord-001397-nrq4ncdf.txt txt: ./txt/cord-001397-nrq4ncdf.txt summary: Avenues for additional studies include determining if the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence as well as investigating the host responses that allow vector borne flavivirus replication without detrimental effects on infected cells. The SL1 structure is essential for viral replication and acts as a promoter which is targeted initially by NS5 and then delivered to the 3 0 end via cyclization (Filomatori et al., 2006; Zhang et al., 2008; Lodeiro et al., 2009) Although there is low nucleotide conservation between flaviviruses and different CS homology (Hahn et al., 1987) , the 5 0 UTRs of TBFVs share the same genomic organization as the MBFVs (Kofler et al., 2006) Structural proteins Capsid (C) 11 kDa, 114 aa Cytosol/nucleus The capsid protein is a dimeric alpha-helical (Jones et al., 2003) protein and assembles into an icosahedral structure, measuring 30 nm in diameter, which initiates encapsidation of the associated genomic RNA in virus-induced membrane invaginations of the ER (Welsch et al., 2009 ). abstract: In nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine. These viruses account for considerable human morbidity and mortality worldwide. Increasing and substantial evidence of viral persistence in humans, which includes the isolation of RNA by RT-PCR and infectious virus by culture, continues to be reported. Viral persistence can also be established in vitro in various human, animal, arachnid and insect cell lines in culture. Although some research has focused on the potential roles of defective virus particles, evasion of the immune response through the manipulation of autophagy and/or apoptosis, the precise mechanism of flavivirus persistence is still not well understood. We propose additional research for further understanding of how viral persistence is established in different systems. Avenues for additional studies include determining if the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence as well as investigating the host responses that allow vector borne flavivirus replication without detrimental effects on infected cells. Such studies might shed more light on the viral-host relationships, and could be used to unravel the mechanisms for establishment of persistence. url: https://academic.oup.com/femspd/article-pdf/71/2/137/17943040/71-2-137.pdf doi: 10.1111/2049-632x.12178 id: cord-292289-amzzdh3t author: Mochizuki, M. title: Inhibitory effects of recombinant feline interferon on the replication of feline enteropathogenic viruses in vitro date: 1994-03-31 words: 3226.0 sentences: 158.0 pages: flesch: 57.0 cache: ./cache/cord-292289-amzzdh3t.txt txt: ./txt/cord-292289-amzzdh3t.txt summary: Compared with each virus control culture of fcwf-4 cells, yields of rotavirus, feline panleukopenia virus (FPLV), feline calicivirus and feline infectious peritonitis coronavirus were reduced by ranges of 1.3 to ⩽3.1 log10, 0.6 log2, 0.8 to 3.7 log10 and 0.5 to 0.6 log10, respectively, in the cultures continuously treated with 10 to 10000 U of the rFeIFN. Preformed monolayers of fcwf-4, CRFK or MDCK cells in 24-well cell culture plates (Coming, New York) were treated with the rFelFN at 37°C for 24 h before challenge of VSV, FHV, rotavirus, FIPV and FCV. (2) FPLV Growth of the TU 1 strain in both fcwf-4 and CRFK cell cultures was slightly but IFN dose-dependently inhibited when the cells were continuously treated with the rFelFN for 96 h (Table 1) . The results indicate that certain degrees of antiviral effects against rotavirus, FIPV, FCV and FPLV can be generated in the feline cells by treatment with the rFelFN. abstract: Abstract Antiviral activities of a recombinant feline interferon (rFeIFN) KT-80 were evaluated against feline enteropathogenic viruses in feline and canine cell lines. Sensitivity to antiviral activities of the rFeIFN varied with cell types; Felis catus whole fetus (fcwf-4) cells were more sensitive than Crandell feline kidney cells, but no sensitivity was found for Madin-Darby canine kidney cells when vesicular stomatitis virus was used as a challenge virus. Reductions were generally IFN dose-dependent and were more consistent when the cells were continuously treated with the rFeIFN than when they were pretreated only before viral challenge. Compared with each virus control culture of fcwf-4 cells, yields of rotavirus, feline panleukopenia virus (FPLV), feline calicivirus and feline infectious peritonitis coronavirus were reduced by ranges of 1.3 to ⩽3.1 log10, 0.6 log2, 0.8 to 3.7 log10 and 0.5 to 0.6 log10, respectively, in the cultures continuously treated with 10 to 10000 U of the rFeIFN. The yield reduction of FPLV was considered to be in part attributable to inhibition of cell growth by the rFeIFN supplemented in the medium. url: https://api.elsevier.com/content/article/pii/0378113594900957 doi: 10.1016/0378-1135(94)90095-7 id: cord-275795-ee7qyw5h author: Monette, Anne title: T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders date: 2018-10-24 words: 28265.0 sentences: 1205.0 pages: flesch: 38.0 cache: ./cache/cord-275795-ee7qyw5h.txt txt: ./txt/cord-275795-ee7qyw5h.txt summary: We focus on immunity generated against both natural infection and vaccination, where a steady shift in conferred vaccination immunogenicity is observed from quantifying activated and proliferating, long-lived effector memory T cell subsets, as the prominent biomarkers of long-term immunity against viruses and their associated disorders causing high morbidity and mortality rates. Since that time, the occurrence of epidemics and outbreaks are now at lower risk, following the introduction of massive vaccination programs able to induce immune system targeting of viruses causing severe disorders affecting distinct geographical locations, and with many epidemiological reports demonstrating long-term efficacy of viral control of non-naïve populations. This approach is being developed to use virus-infected cell-killing antibodies that produce an antiviral environment; these termed antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, which are predicted to link innate and adaptive immune responses, and is becoming possible due to new technologies for rapid isolation and characterization of monoclonal antibodies targeting conserved regions of influenza virus, reviewed in Jegaskanda et al. abstract: Continuous epidemiological surveillance of existing and emerging viruses and their associated disorders is gaining importance in light of their abilities to cause unpredictable outbreaks as a result of increased travel and vaccination choices by steadily growing and aging populations. Close surveillance of outbreaks and herd immunity are also at the forefront, even in industrialized countries, where previously eradicated viruses are now at risk of re-emergence due to instances of strain recombination, contractions in viral vector geographies, and from their potential use as agents of bioterrorism. There is a great need for the rational design of current and future vaccines targeting viruses, with a strong focus on vaccine targeting of adaptive immune effector memory T cells as the gold standard of immunity conferring long-lived protection against a wide variety of pathogens and malignancies. Here, we review viruses that have historically caused large outbreaks and severe lethal disorders, including respiratory, gastric, skin, hepatic, neurologic, and hemorrhagic fevers. To observe trends in vaccinology against these viral disorders, we describe viral genetic, replication, transmission, and tropism, host-immune evasion strategies, and the epidemiology and health risks of their associated syndromes. We focus on immunity generated against both natural infection and vaccination, where a steady shift in conferred vaccination immunogenicity is observed from quantifying activated and proliferating, long-lived effector memory T cell subsets, as the prominent biomarkers of long-term immunity against viruses and their associated disorders causing high morbidity and mortality rates. url: https://www.sciencedirect.com/science/article/pii/S1937644818300844 doi: 10.1016/bs.ircmb.2018.07.006 id: cord-003492-rodqdtfj author: Montaner-Tarbes, Sergio title: Key Gaps in the Knowledge of the Porcine Respiratory Reproductive Syndrome Virus (PRRSV) date: 2019-02-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine diseases in the world. It is causing an enormous economic burden due to reproductive failure in sows and a complex respiratory syndrome in pigs of all ages, with mortality varying from 2 to 100% in the most extreme cases of emergent highly pathogenic strains. PRRSV displays complex interactions with the immune system and a high mutation rate, making the development, and implementation of control strategies a major challenge. In this review, the biology of the virus will be addressed focusing on newly discovered functions of non-structural proteins and novel dissemination mechanisms. Secondly, the role of different cell types and viral proteins will be reviewed in natural and vaccine-induced immune response together with the role of different immune evasion mechanisms focusing on those gaps of knowledge that are critical to generate more efficacious vaccines. Finally, novel strategies for antigen discovery and vaccine development will be discussed, in particular the use of exosomes (extracellular vesicles of endocytic origin). As nanocarriers of lipids, proteins and nucleic acids, exosomes have potential effects on cell activation, modulation of immune responses and antigen presentation. Thus, representing a novel vaccination approach against this devastating disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391865/ doi: 10.3389/fvets.2019.00038 id: cord-296441-682uop9z author: Montoya, María title: Expression Dynamics of Innate Immunity in Influenza Virus-Infected Swine date: 2017-04-21 words: 6328.0 sentences: 327.0 pages: flesch: 52.0 cache: ./cache/cord-296441-682uop9z.txt txt: ./txt/cord-296441-682uop9z.txt summary: Swine IV infection induced interferon (IFN)-alpha and interleukin-6 responses in bronchoalveolar fluids (BALF) at day 3 post infection, as opposed to the other non-swine-adapted virus strains. Swine IV infection induced interferon (IFN)-alpha and interleukin-6 responses in bronchoalveolar fluids (BALF) at day 3 post infection, as opposed to the other nonswine-adapted virus strains. In order to answer these questions, samples from pigs infected with a Swine (H3N2) and four different non-swine-adapted H3N8 IV strains circulating in different animal species (dogs, horses, wild aquatic birds, and seals) from our previous study (16) were analyzed and innate immune responses in the respiratory tract were thoroughly investigated. In order to check IV replication in the lower respiratory tract of pigs, BALF samples collected from pigs killed at day 3, 6, and 21 were tested for gene M of the influenza A virus using a quantitative real-time PCR procedure (17) . abstract: The current circulating swine influenza virus (IV) subtypes in Europe (H1N1, H1N2, and H3N2) are associated with clinical outbreaks of disease. However, we showed that pigs could be susceptible to other IV strains that are able to cross the species barrier. In this work, we extended our investigations into whether different IV strains able to cross the species barrier might give rise to different innate immune responses that could be associated with pathological lesions. For this purpose, we used the same samples collected in a previous study of ours, in which healthy pigs had been infected with a H3N2 Swine IV and four different H3N8 IV strains circulating in different animal species. Pigs had been clinically inspected and four subjects/group were sacrificed at 3, 6, and 21 days post infection. In the present study, all groups but mock exhibited antibody responses to IV nucleoprotein protein. Pulmonary lesions and high-titered viral replication were observed in pigs infected with the swine-adapted virus. Interestingly, pigs infected with avian and seal H3N8 strains also showed moderate lesions and viral replication, whereas equine and canine IVs did not cause overt pathological signs, and replication was barely detectable. Swine IV infection induced interferon (IFN)-alpha and interleukin-6 responses in bronchoalveolar fluids (BALF) at day 3 post infection, as opposed to the other non-swine-adapted virus strains. However, IFN-alpha responses to the swine-adapted virus were not associated with an increase of the local, constitutive expression of IFN-alpha genes. Remarkably, the Equine strain gave rise to a Serum Amyloid A response in BALF despite little if any replication. Each virus strain could be associated with expression of cytokine genes and/or proteins after infection. These responses were observed well beyond the period of virus replication, suggesting a prolonged homeostatic imbalance of the innate immune system. url: https://www.ncbi.nlm.nih.gov/pubmed/28484702/ doi: 10.3389/fvets.2017.00048 id: cord-278050-wl83d6gs author: Morgenstern, Birgit title: Ribavirin and interferon-β synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines date: 2005-01-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Initial in vitro investigations demonstrated type I interferons (IFNs: IFN-α, IFN-β) to inhibit replication of SARS coronavirus (SARS-CoV), but found the nucleoside analogue ribavirin ineffective in Vero cells. In this report, ribavirin was shown to inhibit SARS-CoV replication in five different cell types of animal or human origin at therapeutically achievable concentrations. Since clinical anti-SARS-CoV activity of type I interferons or ribavirin is limited, we investigated the combination of IFN-β and ribavirin. Determination of the virus yield indicated highly synergistic anti-SARS-CoV action of the combination suggesting the consideration of ribavirin plus IFN-β for the treatment of SARS. url: https://www.sciencedirect.com/science/article/pii/S0006291X04027299 doi: 10.1016/j.bbrc.2004.11.128 id: cord-255709-tm3we5sd author: Mossel, Eric C. title: Synergistic Inhibition of Sars-Coronavirus Replication by Type I and Type II IFN date: 2006 words: 893.0 sentences: 60.0 pages: flesch: 60.0 cache: ./cache/cord-255709-tm3we5sd.txt txt: ./txt/cord-255709-tm3we5sd.txt summary: It has been previously shown that treatment of cells with both type I and type II IFN produces an antiviral state greater in magnitude than can be explained by additive effects alone. Cytopathic effect (CPE) was extensive in vehicle-treated groups infected with either SARS-CoV strain at 120 hpi ( Fig. 2A and 2E) , as evident by the reduced monolayer staining with crystal violet. However, the CPE profile observed in Calu-3 cells suggests that the synergistic inhibitory effect on SARS-CoV replication by IFN-β and IFN-γ is not Vero E6 cell specific. It has been known for more than 25 years that treatment of cells with type I and type II IFN potentiates the antiviral response to levels greater than can be explained by simple additive effects. Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/17037585/ doi: 10.1007/978-0-387-33012-9_89 id: cord-001964-iy6qzq58 author: Muñoz-González, Sara title: Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar date: 2016-02-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Two groups with three wild boars each were used: Group A (animals 1 to 3) served as the control, and Group B (animals 4 to 6) was postnatally persistently infected with the Cat01 strain of CSFV (primary virus). The animals, six weeks old and clinically healthy, were inoculated with the virulent strain Margarita (secondary virus). For exclusive detection of the Margarita strain, a specific qRT-PCR assay was designed, which proved not to have cross-reactivity with the Cat01 strain. The wild boars persistently infected with CSFV were protected from superinfection by the virulent CSFV Margarita strain, as evidenced by the absence of clinical signs and the absence of Margarita RNA detection in serum, swabs and tissue samples. Additionally, in PBMCs, a well-known target for CSFV viral replication, only the primary infecting virus RNA (Cat01 strain) could be detected, even after the isolation in ST cells, demonstrating SIE at the tissue level in vivo. Furthermore, the data analysis of the Margarita qRT-PCR, by means of calculated ΔCt values, supported that PBMCs from persistently infected animals were substantially protected from superinfection after in vitro inoculation with the Margarita virus strain, while this virus was able to infect naive PBMCs efficiently. In parallel, IFN-α values were undetectable in the sera from animals in Group B after inoculation with the CSFV Margarita strain. Furthermore, these animals were unable to elicit adaptive humoral (no E2-specific or neutralising antibodies) or cellular immune responses (in terms of IFN-γ-producing cells) after inoculation with the second virus. Finally, a sequence analysis could not detect CSFV Margarita RNA in the samples tested from Group B. Our results suggested that the SIE phenomenon might be involved in the evolution and phylogeny of the virus, as well as in CSFV control by vaccination. To the best of our knowledge, this study was one of the first showing efficient suppression of superinfection in animals, especially in the absence of IFN-α, which might be associated with the lack of innate immune mechanisms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768946/ doi: 10.1371/journal.pone.0149469 id: cord-333208-tibtngy8 author: Muñoz-Moreno, Raquel title: Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection date: 2016-04-26 words: 5867.0 sentences: 311.0 pages: flesch: 45.0 cache: ./cache/cord-333208-tibtngy8.txt txt: ./txt/cord-333208-tibtngy8.txt summary: The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV. Thus, our goal in the current work was to test whether the IFITM family of proteins affected early entry steps of ASFV infection in Vero cell cultures using the cell-adapted Ba71V isolate. Confocal microscopy experiments revealed that, IFITM1 was mainly distributed at the plasma membrane and to a lesser extent in perinuclear compartments, resembling endosomal structures (Fig 3C, lower left panel) , while endogenous IFITM1 was barely detected in Vero cells containing the empty vector (Fig 3C, upper left panel) . abstract: The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. While IFITMs are widely known to inhibit several single-stranded RNA viruses, there are limited reports available regarding their effect in double-stranded DNA viruses. In this work, we have analyzed a possible antiviral function of IFITMs against a double stranded DNA virus, the African swine fever virus (ASFV). Infection with cell-adapted ASFV isolate Ba71V is IFN sensitive and it induces IFITMs expression. Interestingly, high levels of IFITMs caused a collapse of the endosomal pathway to the perinuclear area. Given that ASFV entry is strongly dependent on endocytosis, we investigated whether IFITM expression could impair viral infection. Expression of IFITM1, 2 and 3 reduced virus infectivity in Vero cells, with IFITM2 and IFITM3 having an impact on viral entry/uncoating. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV. url: https://doi.org/10.1371/journal.pone.0154366 doi: 10.1371/journal.pone.0154366 id: cord-285757-fiqx4tll author: Mäkelä, M. J. title: Lack of Induction by Rhinoviruses of Systemic Type I Interferon Production or Enhanced MxA Protein Expression During the Common Cold date: 1999 words: 1825.0 sentences: 97.0 pages: flesch: 50.0 cache: ./cache/cord-285757-fiqx4tll.txt txt: ./txt/cord-285757-fiqx4tll.txt summary: To study whether MxA protein expression is systemically upregulated during rhinovirus infection, blood specimens were collected from 40 patients with common cold and MxA expression in mononuclear cells analyzed by flow cytometry. In conclusion, expression of MxA in blood lymphocytes and an apparently systemic type I interferon response is not induced during rhinovirus infection or during most other cases of common cold in young adult patients. In the present study, the induction of a systemic IFN response as reflected by the expression of MxA protein in blood lymphocytes of patients with rhinovirus infection was examined. Our data suggests that type I IFN production in serum is not comparable to that seen in most other respiratory viral infections in vivo, since the rhinovirus-positive patients had only low or no expression of the MxA protein and no IFN-a/b was detectable in serum samples. abstract: To study whether MxA protein expression is systemically upregulated during rhinovirus infection, blood specimens were collected from 40 patients with common cold and MxA expression in mononuclear cells analyzed by flow cytometry. None of the patients with a confirmed rhinovirus infection (n=15) or with an infection of unknown etiology (n=20) had elevated expression of the MxA protein (median fluorescence intensity, 549 and 582, respectively) when compared to healthy controls (n=11, median 590). Patients with influenza infections had significantly elevated values (n=5, median 750), and interferon could be detected only in serum samples from influenza patients. In conclusion, expression of MxA in blood lymphocytes and an apparently systemic type I interferon response is not induced during rhinovirus infection or during most other cases of common cold in young adult patients. url: https://www.ncbi.nlm.nih.gov/pubmed/10534191/ doi: 10.1007/s100960050370 id: cord-314333-hkyiy1gm author: Nagata, Noriyo title: Mouse-Passaged Severe Acute Respiratory Syndrome-Associated Coronavirus Leads to Lethal Pulmonary Edema and Diffuse Alveolar Damage in Adult but Not Young Mice date: 2008-06-30 words: 6908.0 sentences: 334.0 pages: flesch: 52.0 cache: ./cache/cord-314333-hkyiy1gm.txt txt: ./txt/cord-314333-hkyiy1gm.txt summary: title: Mouse-Passaged Severe Acute Respiratory Syndrome-Associated Coronavirus Leads to Lethal Pulmonary Edema and Diffuse Alveolar Damage in Adult but Not Young Mice Adult mice showed early and acute excessive proinflammatory responses (ie, cytokine storm) in the lungs after SARS-CoV infection, which led to severe pulmonary edema and diffuse alveolar damage. Because advanced age is associated with higher mortality in human SARS patients and SARS-CoV replicates better in aged mice, 6 -10,29 we experimentally infected 6-month-old (adult) female BALB/c mice with F-musX-VeroE6 or the Frankfurt 1 isolate. With regard to the cytokine responses of the mice, the lung homogenates of adult mice on day 1 after inoculation had significantly higher levels of monocyterelated chemokines [ie, MCP-1, macrophage inflammatory protein 1 (MIP-1), and IFN-␥-inducible protein 10 (IP-10)] than those from young mice ( Figure 5 ). abstract: Advanced age is a risk factor of severe acute respiratory syndrome (SARS) in humans. To understand its pathogenesis, we developed an animal model using BALB/c mice and the mouse-passaged Frankfurt 1 isolate of SARS coronavirus (SARS-CoV). We examined the immune responses to SARS-CoV in both young and adult mice. SARS-CoV induced severe respiratory illness in all adult, but not young, mice on day 2 after inoculation with a mortality rate of 30 to 50%. Moribund adult mice showed severe pulmonary edema and diffuse alveolar damage accompanied by virus replication. Adult murine lungs, which had significantly higher interleukin (IL)-4 and lower IL-10 and IL-13 levels before infection than young murine lungs, rapidly produced high levels of proinflammatory chemokines and cytokines known to induce macrophage and neutrophil infiltration and activation (eg, tumor necrosis factor-α). On day 2 after inoculation, young murine lungs produced not only proinflammatory cytokines but also IL-2, interferon-γ, IL-10, and IL-13. Adult mice showed early and acute excessive proinflammatory responses (ie, cytokine storm) in the lungs after SARS-CoV infection, which led to severe pulmonary edema and diffuse alveolar damage. Intravenous injection with anti-tumor necrosis factor-α antibody 3 hours after infection had no effect on SARS-CoV infection. However, intraperitoneal interferon-γ injection protected adult mice from the lethal respiratory illness. The experimental model described here may be useful for elucidating the pathophysiology of SARS and for evaluating therapies to treat SARS-CoV infection. url: https://api.elsevier.com/content/article/pii/S0002944010619219 doi: 10.2353/ajpath.2008.071060 id: cord-256998-or73in8m author: Nguyen, Khue G. title: Localized Interleukin-12 for Cancer Immunotherapy date: 2020-10-15 words: 26912.0 sentences: 1416.0 pages: flesch: 37.0 cache: ./cache/cord-256998-or73in8m.txt txt: ./txt/cord-256998-or73in8m.txt summary: Among the more notable responses in other early preclinical studies, nearly half of mice bearing established B16F10 melanomas experienced complete tumor regression following 2 weekly treatments with pIL-12+EP (124) . In preclinical studies, a single intratumoral injection of mRNA encoding murine IL-12 (mIL-12) increased IFNγ expression and genes associated with a Th1 response in MC38 tumor-bearing mice (190) . In a useful comparison against other cytokines, one study demonstrated that Ad-IFN-γ had no greater antitumor activity than an empty Ad vector, whereas AdmIL-12 induced complete regressions of P815 mastocytomas in >80% of treated mice (219) . Antitumor activity on xenografts of human lung tissues indicated that liposomal encapsulation is a promising approach capable of eliminating tumor cells and inducing lymphocyte infiltration 2 weeks after i.t. injection. Immunotherapy of established tumors in mice by intratumoral injection of an adenovirus vector harboring the human IL-2 cDNA: induction of CD8 + T-cell immunity and NK activity abstract: Interleukin-12 (IL-12) is a potent, pro-inflammatory type 1 cytokine that has long been studied as a potential immunotherapy for cancer. Unfortunately, IL-12's remarkable antitumor efficacy in preclinical models has yet to be replicated in humans. Early clinical trials in the mid-1990's showed that systemic delivery of IL-12 incurred dose-limiting toxicities. Nevertheless, IL-12's pleiotropic activity, i.e., its ability to engage multiple effector mechanisms and reverse tumor-induced immunosuppression, continues to entice cancer researchers. The development of strategies which maximize IL-12 delivery to the tumor microenvironment while minimizing systemic exposure are of increasing interest. Diverse IL-12 delivery systems, from immunocytokine fusions to polymeric nanoparticles, have demonstrated robust antitumor immunity with reduced adverse events in preclinical studies. Several localized IL-12 delivery approaches have recently reached the clinical stage with several more at the precipice of translation. Taken together, localized delivery systems are supporting an IL-12 renaissance which may finally allow this potent cytokine to fulfill its considerable clinical potential. This review begins with a brief historical account of cytokine monotherapies and describes how IL-12 went from promising new cure to ostracized black sheep following multiple on-study deaths. The bulk of this comprehensive review focuses on developments in diverse localized delivery strategies for IL-12-based cancer immunotherapies. Advantages and limitations of different delivery technologies are highlighted. Finally, perspectives on how IL-12-based immunotherapies may be utilized for widespread clinical application in the very near future are offered. url: https://www.ncbi.nlm.nih.gov/pubmed/33178203/ doi: 10.3389/fimmu.2020.575597 id: cord-007783-z1vv63u2 author: Nielsen, Claus H. title: Immunoregulation by Naturally Occurring and Disease-Associated Autoantibodies: Binding to Cytokines and Their Role in Regulation of T-Cell Responses date: 2012-08-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The role of naturally occurring autoantibodies (NAbs) in homeostasis and in disease manifestations is poorly understood. In the present chapter, we review how NAbs may interfere with the cytokine network and how NAbs, through formation of complement-activating immune complexes with soluble self-antigens, may promote the uptake and presentation of self-molecules by antigen-presenting cells. Both naturally occurring and disease-associated autoantibodies against a variety of cytokines have been reported, including NAbs against interleukin (IL)-1α, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon (IFN)-α, IFN-β, IFN-γ, macrophage chemotactic protein-1 and IL-21. NAbs against a variety of other self-antigens have also been reported, and using thyroglobulin as an example we discuss how NAbs are capable of promoting uptake of immune complexes via complement receptors and Fc-receptors on antigen-presenting cells and thereby regulate T-cell activity. Knowledge of the influence of NAbs against cytokines on immune homeostasis is likely to have wide-ranging implications both in understanding pathogenesis and in treatment of many immunoinflammatory disorders, including a number of autoimmune and autoinflammatory diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123141/ doi: 10.1007/978-1-4614-3461-0_9 id: cord-023430-5zuewjv2 author: Nilkaeo, A. title: Interleukin‐18 Inhibition of Oral Carcinoma Cell Proliferation date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Interleukin‐18 (IL‐18), a pro‐inflammatory cytokine that is produced by both lymphoid and nonlymphoid cells, has a critical role in modulation of innate and adaptive immunity. Its primary function in stimulation of IFN‐γ production and stimulation of NK‐cell‐cytotoxic activities makes this cytokine a candidate for cancer immunotherapy. In oral cavity, this cytokine is produced by oral epithelia and carcinoma cells and is related to tumour regression in nude mice bearing salivary adenocarcinoma. However, direct effects of this cytokine on oral cancer cells have not been elucidated. In this project, we investigated IL‐18 effect on an oral carcinoma (KB) cell line. With RT‐PCR technique, KB‐cell line was found to express IL‐18 receptors (IL‐18Rα and IL‐18Rβ), indicating that this oral carcinoma line is a target for IL‐18 study. We showed that recombinant human IL‐18 inhibited KB‐cell proliferation by 17% at concentration of 100 ng/ml (P < 0.05), whereas LDH release by these cells in treatment group and control groups was comparable, indicating that IL‐18 suppression of cell proliferation was not mediated by the induction of cell death. To further address this hypothesis, we found that IL‐18 treatment did not induce apoptotic cell death, as studied by DNA laddering and TUNEL assays. In addition, expression pattern of cell death‐controlling genes (bcl‐2 and bax) was not altered by this cytokine. Findings in these studies indicated that suppression of KB‐cell proliferation may be attributed to control of cell cycle, growth arrest or induction of cell differentiation. The data presented in this project could provide an insight of how cancer cell directly responds to IL‐18, as this cytokine is an important regulator of anticancer mechanisms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169582/ doi: 10.1111/j.0300-9475.2004.01423bg.x id: cord-032183-yqqqe325 author: Ning, Qin title: Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure) date: 2019-05-21 words: 32675.0 sentences: 1658.0 pages: flesch: 43.0 cache: ./cache/cord-032183-yqqqe325.txt txt: ./txt/cord-032183-yqqqe325.txt summary: Patients awaiting liver transplantation because of HBV-related end-stage liver disease or liver cancer should be given nucleoside analogues with strong HBV inhibition and low drug-resistance, or nucleotides analogues combination treatment, in order to reduce viral load and prevent graft re-infection. The objective of antiviral treatment for HBV-ACLF is to reduce viral load at an appreciably high rate, thereby promoting reduction in hepatocyte cell death and improved survival outcomes by prevention of decompensation related multiorgan complications in this group of severely ill patients. Response-Guided Therapy 4006 study [126] suggested continuous treatment with LAM (10 years) delayed clinical progression in patients with chronic hepatitis and advanced fibrosis by significantly reducing the incidence of the risk of hepatocellular carcinoma and hepatic decompensation. abstract: This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation. 1. Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. 2. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. 3. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. 4. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. 5. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). 6. Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498919/ doi: 10.1007/978-94-024-1603-9_5 id: cord-309381-cb80ntxs author: Nogales, Aitor title: Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans date: 2019-09-30 words: 10222.0 sentences: 590.0 pages: flesch: 45.0 cache: ./cache/cord-309381-cb80ntxs.txt txt: ./txt/cord-309381-cb80ntxs.txt summary: IAV RNAs are mainly recognized by the endosomal, membrane-associated PRR Toll-like receptors (TLRs) 3 (double-stranded RNAs, dsRNAs) or 7/8 (ssRNAs), respectively [50, 51] , by the cytoplasmic PRR retinoic acid-inducible gene I (RIG-I), which detects dsRNA and 5 -triphosphates of the negative ssRNA viral genome [50, 52] , generated during replication of multiple viruses, by the NOD-like receptor family member NOD-, LRR-and pyrin domain-containing 3 (NLRP3), which recognizes various stimuli (see below) [53] and by the absent in melanoma 2 (AIM2) protein, recognizing not well-characterized influenza stimuli [54] . Another important SNP (rs34481144) associated with risk of severe influenza in humans from the United States (US) infected with seasonal IAVs is located in the 5 -UTR of the IFITM3 gene [123, 124] . abstract: A large number of human genes associated with viral infections contain single nucleotide polymorphisms (SNPs), which represent a genetic variation caused by the change of a single nucleotide in the DNA sequence. SNPs are located in coding or non-coding genomic regions and can affect gene expression or protein function by different mechanisms. Furthermore, they have been linked to multiple human diseases, highlighting their medical relevance. Therefore, the identification and analysis of this kind of polymorphisms in the human genome has gained high importance in the research community, and an increasing number of studies have been published during the last years. As a consequence of this exhaustive exploration, an association between the presence of some specific SNPs and the susceptibility or severity of many infectious diseases in some risk population groups has been found. In this review, we discuss the relevance of SNPs that are important to understand the pathology derived from influenza A virus (IAV) infections in humans and the susceptibility of some individuals to suffer more severe symptoms. We also discuss the importance of SNPs for IAV vaccine effectiveness. url: https://doi.org/10.3390/pathogens8040168 doi: 10.3390/pathogens8040168 id: cord-034467-jh9msz1c author: Olagoke, Olusola title: Koalas vaccinated against Koala retrovirus respond by producing increased levels of interferon-gamma date: 2020-10-31 words: 2209.0 sentences: 132.0 pages: flesch: 49.0 cache: ./cache/cord-034467-jh9msz1c.txt txt: ./txt/cord-034467-jh9msz1c.txt summary: In the present study, we examined the expression of important koala cytokines, immune markers and host restrictions factors to determine their pre-and post-vaccination levels in northern koalas harbouring endogenous KoRV. Genes targeted included nine cytokines (CCL4L, Interleukin Open Access *Correspondence: oolagoke@usc.edu.au Genecology Research Centre, University of the Sunshine Coast, Sunshine Coast, QLD, Australia (IL)-1β, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-18 and Interferon gamma (IFN-γ), four host restriction factors (BST2, ISG15, RSAD2 and TRIM1) and two T-cell markers (CD4 and CD8β). In addition, none of the host restriction factors tested (BST2, ISG15, RSAD2 and TRIM1) had significant changes in their expression either at 4-or 8-weeks post-vaccination when compared to prevaccination levels. In this cohort of KoRV vaccinated and endogenously infected koalas, a small but significant increase in the expression of IFN-γ at both 4-and 8-weeks post-vaccination was observed, compared to pre-vaccination levels. Our study investigated the expression of four host restriction factors in koalas harbouring endogenous KoRV: BST2, ISG15, RSAD2 and TRIM1. abstract: Koala retrovirus (KoRV) is believed to be in an active state of endogenization into the koala genome. KoRV is present as both an endogenous and exogenous infection in all koalas in northern Australia. KoRV has been linked to koala pathologies including neoplasia and increased susceptibility to Chlamydia. A KoRV vaccine recently trialled in 10 northern koalas improved antibody response and reduced viral load. This communication reports the expression of key immune genes underlining the innate and adaptive immune response to vaccination in these northern koalas. The results showed that prior to vaccination, IL-8 was expressed at the highest levels, with at least 200-fold greater expression compared to other cytokines, while CD8 mRNA expression was significantly higher than CD4 mRNA expression level. Interferon-γ was up-regulated at both 4- and 8-weeks post-vaccination while IL-8 was down-regulated at 8-weeks post-vaccination. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602773/ doi: 10.1186/s12985-020-01442-7 id: cord-328804-f7etlk5i author: Olofsson, Peter title: Arthritis suppression by NADPH activation operates through an interferon-β pathway date: 2007-05-09 words: 7779.0 sentences: 368.0 pages: flesch: 48.0 cache: ./cache/cord-328804-f7etlk5i.txt txt: ./txt/cord-328804-f7etlk5i.txt summary: Hence, global gene-expression profiling on inguinal lymph nodes was performed 10 days after the induction of pristane-induced arthritis (PIA) and phytol administration. To analyze the in vivo effects of the NADPH oxidase activator phytol versus the effects of the arthritis-inducing compound pristane, global gene-expression profiling was performed. By studying gene-expression profiles and performing pathway analysis, we have identified the importance of an IFN-β-dependent pathway as one molecular mechanism for the arthritis-ameliorating efficacy of NADPH oxidaseactivating compounds. To obtain a more detailed understanding of the molecular mechanism of this regulation, gene-expression profiling experiments were performed on inguinal lymph nodes from rats with pharmacologically (phytol) and genetically (Ncf1) modified NADPH oxidase activity. In this study, we used global gene-expression analysis and quantitative real-time PCR techniques in four separate arthritis experiments in rats to investigate the downstream effects of preventive arthritis treatment with the NADPH oxidase activator phytol. abstract: BACKGROUND: A polymorphism in the activating component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, neutrophil cytosolic factor 1 (NCF1), has previously been identified as a regulator of arthritis severity in mice and rats. This discovery resulted in a search for NADPH oxidase-activating substances as a potential new approach to treat autoimmune disorders such as rheumatoid arthritis (RA). We have recently shown that compounds inducing NCF1-dependent oxidative burst, e.g. phytol, have a strong ameliorating effect on arthritis in rats. However, the underlying molecular mechanism is still not clearly understood. The aim of this study was to use gene-expression profiling to understand the protective effect against arthritis of activation of NADPH oxidase in the immune system. RESULTS: Subcutaneous administration of phytol leads to an accumulation of the compound in the inguinal lymph nodes, with peak levels being reached approximately 10 days after administration. Hence, global gene-expression profiling on inguinal lymph nodes was performed 10 days after the induction of pristane-induced arthritis (PIA) and phytol administration. The differentially expressed genes could be divided into two pathways, consisting of genes regulated by different interferons. IFN-γ regulated the pathway associated with arthritis development, whereas IFN-β regulated the pathway associated with disease protection through phytol. Importantly, these two molecular pathways were also confirmed to differentiate between the arthritis-susceptible dark agouti (DA) rat, (with an Ncf-1(DA )allele that allows only low oxidative burst), and the arthritis-protected DA.Ncf-1(E3 )rat (with an Ncf1(E3 )allele that allows a stronger oxidative burst). CONCLUSION: Naturally occurring genetic polymorphisms in the Ncf-1 gene modulate the activity of the NADPH oxidase complex, which strongly regulates the severity of arthritis. We now show that the Ncf-1 allele that enhances oxidative burst and protects against arthritis is operating through an IFN-β-associated pathway, whereas the arthritis-driving allele operates through an IFN-γ-associated pathway. Treatment of arthritis-susceptible rats with an NADPH oxidase-activating substance, phytol, protects against arthritis. Interestingly, the treatment led to a restoration of the oxidative-burst effect and induction of a strikingly similar IFN-β-dependent pathway, as seen with the disease-protective Ncf1 polymorphism. url: https://www.ncbi.nlm.nih.gov/pubmed/17490473/ doi: 10.1186/1741-7007-5-19 id: cord-298259-r9rn0yyz author: Omatsu, Tsutomu title: Induction and sequencing of Rousette bat interferon α and β genes date: 2008-07-15 words: 2981.0 sentences: 202.0 pages: flesch: 63.0 cache: ./cache/cord-298259-r9rn0yyz.txt txt: ./txt/cord-298259-r9rn0yyz.txt summary: To investigate the function of type I IFNs upon viral infection in bats, the nucleic acid, and amino acid sequences of Egyptian Rousette (Rousettus aegyptiacus) IFN-α and -β were characterized. Stimulation of bat primary kidney cells (BPKCs) and bat lung cell lines, Tb-1 Lu, with polyinosinic–polycytidylic acid (poly(I:C)) or exogenous bat type I IFNs resulted in increased type I IFNs mRNA expression in BPKCs, but not in Tb-1 Lu. Characterization of the bat IFN-α and -β genes allows understanding of the immune responses upon stimulation in different tissues, thus providing practical strategies for control and treatment of clinically important diseases. These results are important especially for the virus infection, and suggest that future molecular studies on virus infection experiment of bats in vitro will require careful consideration of the differences of type I IFN expression patterns in different cell types. These data suggested that Ebola virus might evade the anti-viral activity of IFNs in bat cells. abstract: Bats are considered to be natural reservoirs for several viruses of clinical importance, including rabies virus, Nipah virus, and Hendra virus. Type I interferons (IFNs) is an important part of the immune system in the defense against viral infection. To investigate the function of type I IFNs upon viral infection in bats, the nucleic acid, and amino acid sequences of Egyptian Rousette (Rousettus aegyptiacus) IFN-α and -β were characterized. Sequence data indicated that bat IFN-α consists of 562-bp encoded 187-aa, and IFN-β consisted of 558-bp encoded 186-aa. Phylogenetic analysis of the overall identity of IFN-β shared the highest sequence homology with pig IFN-β in both nucleotide and amino acid level. Stimulation of bat primary kidney cells (BPKCs) and bat lung cell lines, Tb-1 Lu, with polyinosinic–polycytidylic acid (poly(I:C)) or exogenous bat type I IFNs resulted in increased type I IFNs mRNA expression in BPKCs, but not in Tb-1 Lu. Characterization of the bat IFN-α and -β genes allows understanding of the immune responses upon stimulation in different tissues, thus providing practical strategies for control and treatment of clinically important diseases. These results are important especially for the virus infection, and suggest that future molecular studies on virus infection experiment of bats in vitro will require careful consideration of the differences of type I IFN expression patterns in different cell types. url: https://www.ncbi.nlm.nih.gov/pubmed/18436311/ doi: 10.1016/j.vetimm.2008.03.004 id: cord-001848-idmj2d7p author: Onabajo, Olusegun O. title: Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells date: 2015-11-01 words: 7203.0 sentences: 335.0 pages: flesch: 47.0 cache: ./cache/cord-001848-idmj2d7p.txt txt: ./txt/cord-001848-idmj2d7p.txt summary: We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Previously, we showed that transient transfection of an expression construct that generates IFN-l4 protein induced interferon signaling, with activation of interferon-stimulated genes (ISGs) and generation of antiviral response in HepG2, a human hepatoma cell line (Prokunina-Olsson and others 2013). The stable HepG2-ISRE-Luc cells were transfected with corresponding constructs in 96-well plates; untransfected cells were treated with human recombinant interferons-IFNa (2 ng/mL; PBL Assay Science) or custom IFN-l3 (10 ng/ mL). Previously, by performing Western blot analysis, we were unable to detect IFN-l4 in culture media of HepG2 cells transiently transfected with an IFN-l4-producing construct, even though this transfection resulted in strong activation of interferon signaling (Prokunina-Olsson and others 2013). IFN-l4 was detectable in culture media of IFNL4-transfected PHHs and HepG2 cells, but not in corresponding Halo-transfected cells (Fig. 2B) . abstract: Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be generated only in individuals carrying a ΔG frame-shift allele of an exonic genetic variant (rs368234815-ΔG/TT). The rs368234815-ΔG allele is strongly associated with decreased clearance of hepatitis C virus (HCV) infection. Here, we further explored the biological function of IFN-λ4 expressed in human hepatic cells—a hepatoma cell line HepG2 and fresh primary human hepatocytes (PHHs). We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Not only did we observe significant intracellular retention of IFN-λ4 but also detected secreted IFN-λ4 in the culture media of expressing cells. Secreted IFN-λ4 induced strong activation of the interferon-stimulated genes (ISGs) in IFN-λ4-expressing and surrounding cells in transwell assays. Specifically, in PHHs, secreted IFN-λ4 induced expression of the CXCL10 transcript and a corresponding pro-inflammatory chemokine, IP-10. In IFN-λ4-expressing HepG2 cells, we also observed decreased proliferation and increased cell death. All IFN-λ4-induced phenotypes—activation of ISGs, decreased proliferation, and increased cell death—could be inhibited by an anti-IFN-λ4-specific antibody. Our study offers new insights into biology of IFN-λ4 and its possible role in HCV clearance. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642834/ doi: 10.1089/jir.2014.0161 id: cord-274816-6xpma224 author: Onal, Merih title: Can secondary lymphoid organs exert a favorable effect on the mild course of COVID-19 in children? date: 2020-10-27 words: 1426.0 sentences: 76.0 pages: flesch: 43.0 cache: ./cache/cord-274816-6xpma224.txt txt: ./txt/cord-274816-6xpma224.txt summary: Palatine and pharyngeal tonsils are important organs of the immune system, and they protect the body from pathogens invading the upper respiratory tract, especially in young children [8] . In a study on patients with hypertrophic adenoid tissue, recurrent upper and lower respiratory tract infections were demonstrated along with high serum myeloperoxidase levels (indicating neutrophil activation), increased serum eosinophilic cationic protein levels (indicating eosinophil activation) and high CD 163 glycoprotein levels (indicating monocyte/macrophage activation) [15] . It is known that human tonsils are immunologically reactive lymphoid organs carrying out humoral and cellular immunity functions as a response to various antigens and displaying B and T cell activity [16] . In the same study, although a difference was expected in tonsillar hypertrophy and recurrent tonsillitis groups in terms of the levels of interferons (IFN-a, IFN-b, IFN-c, IL-28, IL-29) , which are cytokines with antiviral activity and whose expression is induced by viral infection, not detected. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/33108239/ doi: 10.1080/00016489.2020.1814965 id: cord-255997-oer5lxxr author: Onodi, Fanny title: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date: 2020-07-10 words: 4209.0 sentences: 254.0 pages: flesch: 53.0 cache: ./cache/cord-255997-oer5lxxr.txt txt: ./txt/cord-255997-oer5lxxr.txt summary: Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Interestingly, pDC responded to SARS-CoV-2 by a complete activation program, including diversification into effector subsets, production of type I and type III IFN, as well as inflammatory cytokines. We also showed that hydroxychloroquine, an antimalarial drug proposed for treatment of COVID-19 patients (Das et al., 2020; Mahévas et al., 2020) , inhibits SARS-CoV-2-induced pDC activation and IFN production in a dose-dependent manner. Following 24 hours of culture, we found that HCQ inhibited pDC diversification in response to SARS-CoV-2, which is similar to the decrease observed with Flu, used as a positive control ( Fig 4A) . abstract: Several studies have analyzed antiviral immune pathways in severe COVID-19 patients. However, the initial steps of antiviral immunity are not known. Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not permissive to SARS-CoV-2 infection. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed checkpoint molecules at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2- and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Our results indicate that pDC may represent a major player in the first line of defense against SARS-CoV-2 infection, and call for caution in the use of hydroxychloroquine in the early treatment of the disease. url: https://doi.org/10.1101/2020.07.10.197343 doi: 10.1101/2020.07.10.197343 id: cord-001359-c1uom5f7 author: Oslund, Karen L. title: Synergistic Up-Regulation of CXCL10 by Virus and IFN γ in Human Airway Epithelial Cells date: 2014-07-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Airway epithelial cells are the first line of defense against viral infections and are instrumental in coordinating the inflammatory response. In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. The synergism also occurred when the cells were treated with IFN γ and a viral replication mimicker (dsRNA) both in vitro and in vivo. Despite the requirement of type I interferon (IFNAR) signaling in dsRNA-induced CXCL10, the synergism was independent of the IFNAR pathway since it wasn’t affected by the addition of a neutralizing IFNAR antibody or the complete lack of IFNAR expression. Furthermore, the same synergistic effect was also observed when a CXCL10 promoter reporter was examined. Although the responsive promoter region contains both ISRE and NFκB sites, western blot analysis indicated that the combined treatment of IFN γ and dsRNA significantly augmented NFκB but not STAT1 activation as compared to the single treatment. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102466/ doi: 10.1371/journal.pone.0100978 id: cord-296948-sqxrwgif author: Paquin, Ashley title: Comparative Functional Analysis of 12 Mammalian IFN-λ4 Orthologs date: 2016-01-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: IFN-λ4 is a novel type-III interferon with strong clinical significance in humans. Only a subset of individuals—up to 10% of Asians, 50% of Europeans, and 90% of Africans—carry the ΔG allele of a genetic variant rs368234815-TT/ΔG and are genetically able to produce IFN-λ4 protein. Carriers of the ΔG allele have impaired ability to clear infection with hepatitis C virus (HCV). IFN-λ4 is also predicted to exist and be functionally important in several nonhuman mammals. In this study, we present the first comparative analysis of 12 mammalian IFN-λ4 orthologs in a human hepatic cell line, HepG2, which supports signaling of the human IFN-λ4. We show that despite differences in protein sequences, functional properties of the recombinant human and nonhuman IFN-λ4 proteins are comparable—they are all expressed as predominantly cytoplasmic proteins that are biologically active for induction of interferon signaling. We show that several IFN-λ4 orthologs can be detected by Western blotting, flow cytometry, and confocal imaging using a monoclonal antibody developed for the human IFN-λ4. Studies of IFN-λ4 in animals should help improve our understanding of the biology of this novel clinically important interferon in normal and disease conditions. url: https://doi.org/10.1089/jir.2015.0096 doi: 10.1089/jir.2015.0096 id: cord-268341-103xf3dw author: Parra, Beatriz title: Kinetics of Cytokine mRNA Expression in the Central Nervous System Following Lethal and Nonlethal Coronavirus-Induced Acute Encephalomyelitis date: 1997-07-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The potential role(s) of cytokines in the reduction of infectious virus and persistent viral infection in the central nervous system was examined by determining the kinetics of cytokine mRNA expression following infection with the neurotropic JHM strain of mouse hepatitis virus. Mice were infected with an antibody escape variant which produces a nonlethal encephalomyelitis and compared to a clonal virus population which produces a fulminant fatal encephalomyelitis. Infection with both viruses induced the accumulation of mRNAs associated with Th1- and Th2-type cytokines, including IFN-γ, IL-4, and IL-10. Peak mRNA accumulations were coincident with the clearance of virus and there was no obvious differences between lethally and nonlethally infected mice. TNF-α mRNA was induced more rapidly in lethally infected mice compared to mice undergoing a nonfatal encephalomyelitis. Rapid transient increases in the mRNAs encoding IL-12, iNOS, IL-1α, IL-1β, and IL-6 occurred following infection. Nonlethal infections were associated with increased IL-12, IL-1β, and earlier expression of IL-6, while lethal infections were associated with increased iNOS and IL-1α mRNA. These data suggest a rapid but differential response within the central nervous system cells to infection by different JHMV variants. However, neither the accumulation nor kinetics of induction provide evidence to distinguish lethal infections from nonlethal infections leading to a persistent infection. Accumulation of both Th1 and Th2 cytokines in the central nervous system of JHMV-infected mice is consistent with the participation of both cytokines and cell immune effectors during resolution of acute viral-induced encephalomyelitis. url: https://api.elsevier.com/content/article/pii/S004268229798613X doi: 10.1006/viro.1997.8613 id: cord-335245-1eksm537 author: Pattyn, Els title: HyperISGylation of Old World Monkey ISG15 in Human Cells date: 2008-06-18 words: 7011.0 sentences: 419.0 pages: flesch: 54.0 cache: ./cache/cord-335245-1eksm537.txt txt: ./txt/cord-335245-1eksm537.txt summary: Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Western blot analysis on total cell lysates containing b-ME confirmed ISGylation of UbcH10, H13 and H17 with AgmISG15 but not with HuISG15, as seen by a 15 kDa shift upon staining with anti-V5 Ab detecting the ectopic expressed UbcH proteins (Figure 3a ,b and Figure S2a ). Previous studies using Western blot analysis in HekT cells revealed Hu or MoISG15 conjugation to substrates such as UbcH13 only upon co-transfection of at least UbE1L -and generally also UbcH/M8or upon IFN stimulation. The effect of mutating HuISG15 residues situated near the predicted UbE1L interface and the different allelic variants on conjugation to UbcH proteins is shown in Figure 5a and S3a. As shown in Figure 5c , mutation of D133N and QIT31-33KIA in the HuISG15 N89D variant further enhanced its ISGylation in human HekT cells. abstract: BACKGROUND: ISG15 is an Ubiquitin-like protein, highly induced by Type I Interferons. Upon the cooperative activity of specific Ubiquitinating enzymes, ISG15 can be conjugated to its substrates. Increasing evidence points to a role for protein ISGylation in anti-viral and anti-tumoral defense. PRINCIPAL FINDINGS: We identified ISG15 from Old World Monkeys (OWm) as a hyper-efficient protein modifier. Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Moreover, the substrates of OWmISG15 identified upon Tandem Affinity Purification followed by LC-MS/MS identification largely outnumbered these of HuISG15 itself. Several Ubiquitin-Conjugating enzymes were identified as novel ISGylated substrates. Introduction of a N89D mutation in HuISG15 improved its ISGylation capacity, and additional Q31K/T33A/D133N mutations yielded a HuISG15 variant with an ISGylation efficiency comparable to OWmISG15. Homology modeling and structural superposition situate N89 in the interaction interface with the Activating enzyme. Analysis of the UbE1L residues in this interface revealed a striking homology between OWmUbE1L and HuUbE1, the Activating enzyme of Ubiquitin. In line with this observation, we found efficient activation of AgmISG15, but not HuISG15 or MoISG15, by HuUbE1, thus providing a likely explanation for OWm hyperISGylation. CONCLUSIONS: This study discloses the poor conjugation competence of HuISG15 compared to OWmISG15 and maps the critical determinants for efficient conjugation. HyperISGylation may greatly assist ISGylation studies and may enhance its function as positive regulator of Interferon-related immune responses or as anti-tumoral modulator. url: https://www.ncbi.nlm.nih.gov/pubmed/18560560/ doi: 10.1371/journal.pone.0002427 id: cord-000018-amvlm09p author: Pauli, Eva-K. title: Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression date: 2008-11-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The type I interferon (IFN) system is a first line of defense against viral infections. Viruses have developed various mechanisms to counteract this response. So far, the interferon antagonistic activity of influenza A viruses was mainly observed on the level of IFNβ gene induction via action of the viral non-structural protein 1 (NS1). Here we present data indicating that influenza A viruses not only suppress IFNβ gene induction but also inhibit type I IFN signaling through a mechanism involving induction of the suppressor of cytokine signaling-3 (SOCS-3) protein. Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNα/β, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1) was strongly reduced. This impaired STAT1 activation was not due to the action of viral proteins but rather appeared to be induced by accumulation of viral 5′ triphosphate RNA in the cell. SOCS proteins are potent endogenous inhibitors of Janus kinase (JAK)/STAT signaling. Closer examination revealed that SOCS-3 but not SOCS-1 mRNA levels increase in an RNA- and nuclear factor kappa B (NF-κB)-dependent but type I IFN-independent manner early in the viral replication cycle. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. As a consequence, progeny virus titers were reduced in SOCS-3 deficient cells or in cells were SOCS-3 expression was knocked-down by siRNA. These data provide the first evidence that influenza A viruses suppress type I IFN signaling on the level of JAK/STAT activation. The inhibitory effect is at least in part due to the induction of SOCS-3 gene expression, which results in an impaired antiviral response. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572141/ doi: 10.1371/journal.ppat.1000196 id: cord-317573-wp2wr3b5 author: Peng, Hui title: Human memory T cell responses to SARS-CoV E protein date: 2006-06-30 words: 4124.0 sentences: 197.0 pages: flesch: 60.0 cache: ./cache/cord-317573-wp2wr3b5.txt txt: ./txt/cord-317573-wp2wr3b5.txt summary: In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-γ and IL-2 following stimulation with a pool of 9 peptides overlapping the entire E protein sequence. To assess memory T cell response specific for E protein after SARS-CoV infection in humans, PBMCs from individuals who had fully recovered from SARS two years after infection were stimulated with a pool of 9 peptides spanning the entire amino acid sequence of the SARS-CoV E protein, or the cells were stimulated with anti-CD3 and anti-CD28 antibodies under the same culture conditions as positive controls. Similarly, the frequency of SARS-CoV E antigen-specific IFN-g-producing cells determined by IFN-g ELISPOT assay in PBMCs from 8 fully recovered SARS individuals was significantly higher than that of the cells from the normal donor controls in response to E peptides (Fig. 1B) . abstract: E protein is a membrane component of severe acute respiratory syndrome coronavirus (SARS-CoV). Disruption of E protein may reduce viral infectivity. Thus, the SARS-CoV E protein is considered a potential target for the development of antiviral drugs. However, the cellular immune responses to E protein remain unclear in humans. In this study, we found that peripheral blood mononuclear cells (PBMCs) from fully recovered SARS individuals rapidly produced IFN-γ and IL-2 following stimulation with a pool of 9 peptides overlapping the entire E protein sequence. Analysis of the immune responses by flow cytometry showed that both CD4(+) and CD8(+)T cells were involved in the SARS-CoV E-specific immune responses after stimulation with SARS-CoV E peptides. Moreover, the majority of IFN-γ(+)CD4(+)T cells were central memory cells expressing CD45RO(+)CCR7(+)CD62L(−); whereas IFN-γ(+)CD8(+) memory T cells were mostly effector memory cells expressing CD45RO(−)CCR7(−)CD62L(−). The results of T-cell responses to 9 individual peptides indicated that the E protein contained at least two major T cell epitopes (E2 amino acid [aa] 9–26 and E5–6: aa 33–57) which were important in eliciting cellular immune response to SARS-CoV E protein in humans. url: https://www.ncbi.nlm.nih.gov/pubmed/16844400/ doi: 10.1016/j.micinf.2006.05.008 id: cord-315730-fzgxuak7 author: Penman, Sophie L. title: Safety perspectives on presently considered drugs for the treatment of COVID‐19 date: 2020-07-17 words: 12067.0 sentences: 627.0 pages: flesch: 42.0 cache: ./cache/cord-315730-fzgxuak7.txt txt: ./txt/cord-315730-fzgxuak7.txt summary: Owing to their efficacy against viruses (mostly demonstrated in vitro) including influenza, HIV, coronavirus OC43, and SARS-CoV, a large number of clinical trials (>230) have been registered worldwide using chloroquine/hydroxychloroquine alone, or in combination with other drugs (e.g. azithromycin) for the treatment of COVID-19. At the time of writing, the RECOVERY trial (clinical trial identifier NCT04381936) which is the largest randomised control trial so far conducted for the treatment of COVID, has stopped recruiting to the hydroxychloroquine arm (1542 patients compared with 3132 on standard care) because of no beneficial effect either in terms of mortality or hospital stay (P. Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial abstract: Intense effort is underway to evaluate potential therapeutic agents for the treatment of COVID‐19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm‐benefit ratios that may be encountered when treating COVID‐19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life‐threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely‐researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID‐19. url: https://www.ncbi.nlm.nih.gov/pubmed/32681537/ doi: 10.1111/bph.15204 id: cord-278159-afce61g0 author: Perales-Linares, Renzo title: Toll-like receptor 3 in viral pathogenesis: friend or foe? date: 2013-09-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viral infections frequently induce acute and chronic inflammatory diseases, yet the contribution of the innate immune response to a detrimental host response remains poorly understood. In virus-infected cells, double-stranded RNA (dsRNA) is generated as an intermediate during viral replication. Cell necrosis (and the release of endogenous dsRNA) is a common event during both sterile and infectious inflammatory processes. The discovery of Toll-like receptor 3 (TLR3) as an interferon-inducing dsRNA sensor led to the assumption that TLR3 was the master sentinel against viral infections. This simplistic view has been challenged by the discovery of at least three members of the DExd/H-box helicase cytosolic sensors of dsRNA that share with TLR3 the Toll–interleukin-1 receptor (TIR) -adapter molecule TIR domain-containing adaptor protein interferon-β (TRIF) for downstream type I interferon signalling. Data are conflicting on the role of TLR3 in protective immunity against viruses in the mouse model. Varying susceptibility to infection and disease outcomes have been reported in TLR3-immunodeficient mice. Surprisingly, the susceptibility to develop herpes simplex virus-1 encephalitis in humans with inborn defects of the TLR3 pathway varies, and TLR3-deficient humans do not show increased susceptibility to other viral infections. Therefore, a current challenge is to understand the protective versus pathogenic contribution of TLR3 in viral infections. We review recent advances in the identification of TLR3-signalling pathways, endogenous and virus-induced negative regulators of the TLR3 cascade, and discuss the protective versus pathogenic role of TLR3 in viral pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/23909285/ doi: 10.1111/imm.12143 id: cord-337677-ktktqs7b author: Pereda, R. title: Therapeutic effectiveness of interferon alpha 2b treatment for COVID-19 patient recovery date: 2020-08-04 words: 3397.0 sentences: 212.0 pages: flesch: 54.0 cache: ./cache/cord-337677-ktktqs7b.txt txt: ./txt/cord-337677-ktktqs7b.txt summary: Patients received therapy as per the Cuban COVID protocol that included a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN alpha-2b The primary endpoint was the proportion of patients discharged from hospital, secondary was the case fatality rate and several outcomes related to time variables were also evaluated. Two groups of individuals were admitted to the hospital, according to the case classification criteria defined in the Cuban protocol: 1) people with suspected COVID-19 due to clinical respiratory symptoms, such as fever, fatigue, cough, headache, shortness of breath and nasal discharge in the last 14 days; 2) subjects who had contact with a patient with confirmed or is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint abstract: Background Effective antiviral treatments are required to contain the ongoing coronavirus disease 2019 (COVID-19) pandemic. A previous report in 814 patients COVID-19 positive in Cuba provided preliminary therapeutic efficacy evidence with interferon alpha-2b (IFN alpha-2b) from March 11 to April 14, 2020. This study, re-evaluates the contribution of IFN-2b on the evolution of all patients, after 98 days of the epidemic, in a period from March 11 to June 17, 2020. Method A prospective observational study was implemented to monitor a therapeutic intervention with IFN alpha-2b used in the national protocol for COVID-19 attending in Cuba. Were included patients with positive throat swab specimens by real time RT-PCR who gave informed consent and had no contraindications for IFN treatment. Patients received therapy as per the Cuban COVID protocol that included a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN alpha-2b The primary endpoint was the proportion of patients discharged from hospital, secondary was the case fatality rate and several outcomes related to time variables were also evaluated. Results From March 11th until June 17th, 2295 patients had been confirmed SARS-CoV-2 positive in Cuba, 2165 were treated with Heberon Alpha R and 130 received the approved protocol without IFN. The proportion of fully recovered patients was higher in the IFN-treated compared with non-IFN treated group. Prior IFN treatment decreases the likelihood of intensive care and increases the survival after severe or critical diseases. The benefits of IFN were significantly supported by time variables analyzed. Conclusions This second report confirm the preliminary evidences from first for the therapeutic effectiveness of IFN alpha-2b for SARS-Cov-2 infection and postulated that Heberon Alpha R is the main component within the antiviral triad used as a therapeutic intervention in the Cuban protocol COVID-19. url: https://doi.org/10.1101/2020.07.28.20157974 doi: 10.1101/2020.07.28.20157974 id: cord-344093-3bniy5b5 author: Peteranderl, Christin title: The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond date: 2017-03-22 words: 12546.0 sentences: 578.0 pages: flesch: 34.0 cache: ./cache/cord-344093-3bniy5b5.txt txt: ./txt/cord-344093-3bniy5b5.txt summary: A prominent regulator of disease outcome, especially in-but not limited to-respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. (73) Cell death induction, e.g., Bcl-2-associated X protein, caspase-8, Fas-associated protein with death domain, Fas ligand, and TNF-related apoptosis-inducing ligand (TRAIL) dsRNA, polyI:C (4, 110) IAV (4, 5, 10, 115) Sendai virus (110) TRAIL Virus control by apoptosis induction in infected cells IAV (6, 170, 171) Tissue injury by apoptosis of both infected and non-infected alveolar epithelial cells, lung macrophages IAV (5, 7, 10) RSV (137) Necrosis of fibroblasts, dendritic cells, and epithelial cells IAV (146, 147, 168) Increased cellular infiltration CoV (175) Decreased expression of Na,K-ATPase, impaired epithelial fluid reabsorption IAV (11) iNTRODUCTiON In 1957, Isaacs and Lindenmann (1) first recognized the potential of a soluble and probably cell-derived factor to combat influenza virus infection and named this factor interferon [(IFN) from latin interferre, to interfere]. abstract: Interferons (IFNs) are well described to be rapidly induced upon pathogen-associated pattern recognition. After binding to their respective IFN receptors and activation of the cellular JAK/signal transducer and activator of transcription signaling cascade, they stimulate the transcription of a plethora of IFN-stimulated genes (ISGs) in infected as well as bystander cells such as the non-infected epithelium and cells of the immune system. ISGs may directly act on the invading pathogen or can either positively or negatively regulate the innate and adaptive immune response. However, IFNs and ISGs do not only play a key role in the limitation of pathogen spread but have also been recently found to provoke an unbalanced, overshooting inflammatory response causing tissue injury and hampering repair processes. A prominent regulator of disease outcome, especially in—but not limited to—respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. First described as an apoptosis-inducing agent in transformed cells, it is now also well established to rapidly evoke cellular stress pathways in epithelial cells, finally leading to caspase-dependent or -independent cell death. Hereby, pathogen spread is limited; however in some cases, also the surrounding tissue is severely harmed, thus augmenting disease severity. Interestingly, the lack of a strictly controlled and well balanced IFN/TRAIL signaling response has not only been implicated in viral infection but might furthermore be an important determinant of disease progression in bacterial superinfections and in chronic respiratory illness. Conclusively, the IFN/TRAIL signaling axis is subjected to a complex modulation and might be exploited for the evaluation of new therapeutic concepts aiming at attenuation of tissue injury. url: https://doi.org/10.3389/fimmu.2017.00313 doi: 10.3389/fimmu.2017.00313 id: cord-023585-n3lr9z3u author: Phillpotts, Robert title: Interferon prophylaxis of the common cold date: 2003-01-06 words: 1970.0 sentences: 116.0 pages: flesch: 55.0 cache: ./cache/cord-023585-n3lr9z3u.txt txt: ./txt/cord-023585-n3lr9z3u.txt summary: Robert Phillpotts describes the mechanism of interferon action and the future hopes and developments for its use in preventing colds. l~''obert Phillpotts describe~ the mechanism of interferon action and the future hopes and developments for its use in preventing colds. Interferon appears to be the ideal antiviral drug for use in preventing colds; it is extremely potent, and active against a wide range of viruses. intranasal interferon prevents colds In an initial experiment at the Common Cold Unit in Wiltshire, UK, intranasal administration of partially purified human leucocyte interferon to volunteers was shown to prevent colds caused by rhinovirus type 4 (Ref. 5). This question was answered in a further experiment carried out in 1982, in which HulFN a, purified to virtual homogeneity on a monoclonal antibody affinity column was shown to prevent colds caused by another rhinovirus, type 9 (Ref. 6). abstract: Interferon is a potential prophylactic agent for the common cold. But there are problems. The present levels of side-effects that have been observed don't justify its use in the long term. Robert Phillpotts describes the mechanism of interferon action and the future hopes and developments for its use in preventing colds. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172481/ doi: 10.1016/0165-6147(84)90509-1 id: cord-286824-3e534pws author: Pitkäranta, Anne title: Lowered yields of virus-induced interferon production in leukocyte cultures and risk of recurrent respiratory infections in children date: 1999-12-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Objective: To study the correlation between the yield of virus-induced interferon (IFN) production in leukocyte cultures and the risk of recurrent respiratory infections. Methods: A sample of 71 consecutive children enrolled in the Finnish Otitis Media Cohort Study were selected. Children suffering from frequently recurring respiratory infections (FRRIs) were defined as the highest quintile of the entire cohort of 329 children, as regards the number of upper respiratory infections (URIs) and/or episodes of acute otitis media (AOM) during the follow-up period from 2 to 24 months. Results: In the sample of 71 children, there were 18 children with FRRI (≥9 URI and/or ≥4 AOM). Leukocyte cultures, prepared from blood drawn from these 18 children at 6 months of age, produced lower yields of IFN than those of the remaining 53 children, when stimulated with adenovirus (P<0.001), coronavirus (P<0.001) or rhinovirus (P=0.002). The difference in IFN yields was even greater (P<0.001 with all three viruses) if the comparison was made between children with FRRI and those with no or maximally one URI during the follow-up period. When the IFN production capacity induced by rhinovirus was measured at the age of 24 months, a statistically significant difference between the children with FRRI and the others was also seen (P=0.002). Influenza A virus-induced IFN production capacity did not differ between the groups at either age (P=0.209). Conclusions: Lowered IFN responses in children suffering from recurrent URIs and/or AOM may, in a subgroup of the children, be due to a genetic property of the child. However, because of the great interindividual variations, we cannot use the IFN production capacity as such for prediction of forthcoming respiratory infections and/or otitis media. url: https://www.ncbi.nlm.nih.gov/pubmed/10614857/ doi: 10.1016/s1386-6532(99)00056-6 id: cord-279924-09uwhxs9 author: Plaisted, Warren C. title: T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells date: 2014-01-01 words: 5580.0 sentences: 280.0 pages: flesch: 48.0 cache: ./cache/cord-279924-09uwhxs9.txt txt: ./txt/cord-279924-09uwhxs9.txt summary: In this study, we demonstrate that cultured murine NPCs are infected by the neurotropic JHM strain of mouse hepatitis virus (JHMV), which induces acute encephalomyelitis and chronic demyelination when injected intracranially into immunocompetent mice. We co-cultured virus-specific CTLs at diminishing effectorto-target (E:T) ratios with NPCs pulsed with the immunodominant CD8 peptide specific for JHMV spike (S) glycoprotein spanning amino acids 510-518 (S510-518), and treated with IFN-γ to induce MHC class I expression. To confirm the role of IFN-γ as the major cytokine contributing to suppression of JHMV replication in infected NPC cultures, monoclonal antibody blockade against the IFN-γ receptor was performed on NPCs before and during treatment with virusspecific CD4þ T cell enriched media. Impaired expression of MHC class II following IFN-γ-treatment of infected NPCs may be a mechanism employed to subvert detection by infiltrating virus-specific CD4þ T cells. abstract: Neural precursor cells (NPCs) are the subject of intense investigation for their potential to treat neurodegenerative disorders, yet the consequences of neuroinvasive virus infection of NPCs remain unclear. This study demonstrates that NPCs support replication following infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV). JHMV infection leads to increased cell death and dampens IFN-γ-induced MHC class II expression. Importantly, cytokines secreted by CD4+ T cells inhibit JHMV replication in NPCs, and CD8+ T cells specifically target viral peptide-pulsed NPCs for lysis. Furthermore, treatment with IFN-γ inhibits JHMV replication in a dose-dependent manner. Together, these findings suggest that T cells play a critical role in controlling replication of a neurotropic virus in NPCs, a finding which has important implications when considering immune modulation for NPC-based therapies for treatment of human neurologic diseases. url: https://api.elsevier.com/content/article/pii/S0042682213006478 doi: 10.1016/j.virol.2013.11.025 id: cord-005664-n4xv247l author: Plötz, Frans B. title: Mechanical ventilation alters the immune response in children without lung pathology date: 2002-01-15 words: 3292.0 sentences: 182.0 pages: flesch: 41.0 cache: ./cache/cord-005664-n4xv247l.txt txt: ./txt/cord-005664-n4xv247l.txt summary: In the tracheal aspirates the immune balance was characterized by a proinflammatory response pattern, with a significant increase in TNF-α and IL-6 concentrations; concentrations of anti-inflammatory mediators remained very low. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. The major finding of the present study is that exposing infants with normal lung function to 2 h of volatile anesthetics, mechanical ventilation, and cardiac catheterization is associated with remarkable changes in immune responses. We observed a proinflammatory response in the lungs with a significant increase in TNF-α, while antiinflammatory cytokine concentrations in tracheal aspirates remained virtually unchanged, just above the detection level. abstract: Objective: This study was undertaken to examine the hypothesis that mechanical ventilation in association with anesthesia would alter the cytokine profile in infants without preexisting lung pathology. Design and setting: Prospective observational study in pediatric intensive care unit in a university hospital. Patients: Twelve infants who were subjected to an uncomplicated diagnostic cardiac catheterization procedure were studied. All subjects were ventilated with a volume control mode, 0.3 FIO(2), 4 cmH(2)O PEEP, and 10 ml/kg tidal volume. Volatile (servoflurane) anesthetics were given. Measurements and results: Tracheal aspirates and blood samples were obtained before and after 2 h of mechanical ventilation. In tracheal aspirates and in supernatants of stimulated whole-blood cultures cytokine concentrations were measured. In the tracheal aspirates the immune balance was characterized by a proinflammatory response pattern, with a significant increase in TNF-α and IL-6 concentrations; concentrations of anti-inflammatory mediators remained very low. The functional capacity of peripheral blood leukocytes to produce INF-γ, TNF-α, and IL-6 in vitro was significantly decreased. This was accompanied by a significant decrease in the killing activity of natural killer cells. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. In the lungs the immune balance favors a proinflammatory response pattern without detectable concentrations of anti-inflammatory mediators. The Th1 immune response by peripheral blood leukocytes was decreased. The observed change in Th1/Th2 balance in favor of Th2 cytokine activity may be a systemic adaptation to the proinflammatory milieu in the lung. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095146/ doi: 10.1007/s00134-002-1216-7 id: cord-005393-rhji4io9 author: Popko, Brian title: The effects of interferon-γ on the central nervous system date: 1997 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Interferon-gamma (IFN-γ) is a pleotropic cytokine released by T-lymphocytes and natural killer cells. Normally, these cells do not traverse the blood-brain barrier at appreciable levels and, as such, IFN-γ is generally undetectable within the central nervous system (CNS). Nevertheless, in response to CNS infections, as well as during certain disorders in which the CNS is affected, T-cell traffic across the blood-brain barrier increases considerably, thereby exposing neuronal and glial cells to the potent effects of IFN-γ. A large portion of this article is devoted to the substantial circumstantial and experimental evidence that suggests that IFN-γ plays an important role in the pathogenesis of the demyelinating disorder multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Moreover, the biochemical and physiological effects of IFN-γ are discussed in the context of the potential consequences of such activities on the developing and mature nervous systems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091409/ doi: 10.1007/bf02740619 id: cord-273144-er6irjw3 author: Powell, Fiona title: Development of reagents to study the turkey''s immune response: Cloning and characterisation of two turkey cytokines, interleukin (IL)-10 and IL-13 date: 2012-06-15 words: 3956.0 sentences: 246.0 pages: flesch: 58.0 cache: ./cache/cord-273144-er6irjw3.txt txt: ./txt/cord-273144-er6irjw3.txt summary: The availability of genome sequences for other avian species, including the zebrafinch (Warren et al., 2010) , the turkey (Dalloul et al., 2010) and the duck (http://pre.ensembl.org/Anas platyrhyncos/Info/), should allow identification and subsequent characterisation of their immune gene repertoires. Real-time qRT-PCR was used to determine IFN-␥ mRNA expression levels in PHA-stimulated splenocytes (from chicken and turkey) treated with recombinant chicken or turkey IL-10 or mock-transfected COS cell supernatant at various dilutions. Similarly, there was inhibition of IFN-␥ production from PHA-stimulated turkey splenocytes by recombinant chicken and turkey IL-10, although Expression patterns of (A) IL-10 and (B) IL-13 mRNA, as measured by real-time quantitative RT-PCR, in lymphoid tissues, non-lymphoid tissues and digestive tissues of the turkey. At the protein level (72 h post-stimulation), recombinant chicken and turkey IL-10 inhibited the production of IFN-␥ by both chicken and turkey splenocytes at high concentrations, as measured by ELISA, and this effect titrated out with increasing dilution of recombinant IL-10 ( Fig. 3C and D respectively). abstract: The cDNAs of two turkey cytokines, interleukin (IL)-10 and IL-13, were cloned using oligonucleotide primers designed from their chicken orthologues. The coding regions of the chicken and turkey genes are highly conserved, with IL-10 and IL-13 exhibiting 94.1% and 90% nucleotide and 92% and 79.9% amino acid identity respectively. Both showed consistent mRNA expression in turkey lymphoid and gut tissues. Expression in non-lymphoid tissues was more variable but generally highest in the skin and trachea. Recombinant turkey IL-10 was expressed and bioactivity demonstrated by inhibition of IFN-γ synthesis from activated splenocytes. Chicken and turkey IL-10 cross-reacted in functional assays. url: https://www.sciencedirect.com/science/article/pii/S0165242712000864 doi: 10.1016/j.vetimm.2012.03.013 id: cord-351845-bli3qm8w author: Prasad, Kartikay title: Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective date: 2020-06-26 words: 4626.0 sentences: 293.0 pages: flesch: 46.0 cache: ./cache/cord-351845-bli3qm8w.txt txt: ./txt/cord-351845-bli3qm8w.txt summary: Towards this goal, in this study, we have generated a human-SARS-CoV-2 interactome based on recently published RNA-Seq analysis of human adenocarcinomic alveolar basal epithelial (A549) cells infected with SARS-CoV-2, and identified disease-related functional genes that will provide the insights into the patho-J o u r n a l P r e -p r o o f 4 mechanisms of COVID-19. Overall, the analysis demonstrated that the upregulated genes are mainly linked to the host response to SARS-CoV-2 infection, type I interferon signaling and the cytokine-mediated signaling pathway. The PPI network analysis indicates that the pathways are enriched in host response to virus infection, type I interferons signaling, and cytokine activation. [74] reported high SARS-CoV-2 loads very early during infection, suggesting that the virus may have developed arsenals that is able to delay the IFN response by inhibiting innate immune signaling. abstract: The current pandemic of 2019 novel coronavirus disease (COVID-19) caused by a novel virus strain, 2019-nCoV/SARS-CoV-2 have posed a serious threat to global public health and economy. It is largely unknown how the human immune system responds to this infection. A better understanding of the immune response to SARS-CoV-2 will be important to develop therapeutics against COVID-19. Here, we have used transcriptomic profile of human alveolar adenocarcinoma cells (A549) infected with SARS-CoV-2 and employed a network biology approach to generate human-virus interactome. Network topological analysis discovers 15 SARS-CoV-2 targets, which belongs to a subset of interferon (IFN) stimulated genes (ISGs). These ISGs (IFIT1, IFITM1, IRF7, ISG15, MX1, and OAS2) can be considered as potential candidates for drug targets in the treatments of COVID-19. We have identified significant interaction between ISGs and TLR3 agonists, like poly I: C, and imiquimod, and suggests that TLR3 agonists can be considered as a potential drug for drug repurposing in COVID-19. Our network centric analysis suggests that moderating the innate immune response is a valuable approach to target COVID-19. url: https://www.sciencedirect.com/science/article/pii/S0141813020336837?v=s5 doi: 10.1016/j.ijbiomac.2020.06.228 id: cord-343824-00mqmpzw author: Qian, Wei title: The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3 date: 2017-07-03 words: 6217.0 sentences: 333.0 pages: flesch: 50.0 cache: ./cache/cord-343824-00mqmpzw.txt txt: ./txt/cord-343824-00mqmpzw.txt summary: title: The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3 Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. Hence, binding of the NS1 protein to dsRNA, RIG-I, and TRIM25 has not established that these NS1 interactions are responsible for inhibiting the activation of IRF3 and IFN transcription. These data reveal a novel mechanism for how the influenza A virus NS1 protein induces inhibition of the host IFN production and may provide a potential target for antiviral drug development. However, our study demonstrated that the influenza A virus NS1 ED targets TRAF3, subsequently inhibits IFN production, implying that TRAF3 is a key factor involved for IAV to escape host innate immune responses. abstract: Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3). This results in an attenuation of the type I IFN signaling pathway. We found that the NS1 C-terminal ED (named NS1/126-225) inhibits the active caspase activation and recruitment domain-containing form of RIG-I [RIG-I(N)]-induced IFN-β reporter activity, the phosphorylation of IRF3, and the induction of IFN-β. Further analysis showed that NS1/126-225 binds to TRAF3 through the TRAF domain, subsequently decreasing TRAF3 K63-linked ubiquitination. NS1/126-225 binding also disrupted the formation of the mitochondrial antiviral signaling (MAVS)–TRAF3 complex, increasing the recruitment of IKKε to MAVS; ultimately shutting down the RIG-I(N)-mediated signal transduction and cellular antiviral responses. This attenuation of cellular antiviral responses leads to evasion of the innate immune response. Taken together, our findings offer an important insight into the interplay between the influenza virus and host innate immunity. url: https://www.ncbi.nlm.nih.gov/pubmed/28717359/ doi: 10.3389/fimmu.2017.00779 id: cord-299756-m0va36er author: Raaben, Matthijs title: Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo date: 2009-08-03 words: 4568.0 sentences: 258.0 pages: flesch: 54.0 cache: ./cache/cord-299756-m0va36er.txt txt: ./txt/cord-299756-m0va36er.txt summary: As the BALB/c and the IFNAR-/129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Furthermore, gene expression profiling of 129SvEv mice lacking the type I IFN receptor, which are not able to control the MHV infection [11] , allowed us to identify type I IFN-independent transcriptional responses. To study the role of type I IFN-independent and -dependent gene expression in the control of MHV infection in vivo in more detail, we next made use of the IFNAR-/-mice [30] . Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. abstract: BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo. url: https://www.ncbi.nlm.nih.gov/pubmed/19650917/ doi: 10.1186/1471-2164-10-350 id: cord-329190-kv9n2qj3 author: Rabaan, Ali A. title: A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective date: 2017-09-01 words: 8886.0 sentences: 433.0 pages: flesch: 44.0 cache: ./cache/cord-329190-kv9n2qj3.txt txt: ./txt/cord-329190-kv9n2qj3.txt summary: The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The Medline database was searched using combinations and variations of terms, including ''Middle East respiratory syndrome coronavirus'', ''MERS-CoV'', ''SARS'', ''therapy'', ''molecular'', ''vaccine'', ''prophylactic'', ''S protein'', ''DPP4'', ''heptad repeat'', ''protease'', ''inhibitor'', ''anti-viral'', ''broad-spectrum'', ''interferon'', ''convalescent plasma'', ''lopinavir ritonavir'', ''antibodies'', ''antiviral peptides'' and ''live attenuated viruses''. A position paper on the evidence base for specific MERS-CoV therapies, published by Public Health England (PHE) and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO), suggested that benefit was likely to exceed risk for convalescent plasma, lopinavir-ritonavir, IFNs and monoclonal/polyclonal antibodies, while, by contrast, for ribavirin monotherapy and corticosteroids it was considered that the risks would outweigh the benefits [42] . abstract: There have been 2040 laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 34.9 %. There is no specific therapy. The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The development of specific therapies and vaccines is therefore urgently required. We examine existing and potential therapies and vaccines from a molecular perspective. These include viral S protein targeting; inhibitors of host proteases, including TMPRSS2, cathepsin L and furin protease, and of viral M(pro) and the PL(pro) proteases; convalescent plasma; and vaccine candidates. The Medline database was searched using combinations and variations of terms, including ‘Middle East respiratory syndrome coronavirus’, ‘MERS-CoV’, ‘SARS’, ‘therapy’, ‘molecular’, ‘vaccine’, ‘prophylactic’, ‘S protein’, ‘DPP4’, ‘heptad repeat’, ‘protease’, ‘inhibitor’, ‘anti-viral’, ‘broad-spectrum’, ‘interferon’, ‘convalescent plasma’, ‘lopinavir ritonavir’, ‘antibodies’, ‘antiviral peptides’ and ‘live attenuated viruses’. There are many options for the development of MERS-CoV-specific therapies. Currently, MERS-CoV is not considered to have pandemic potential. However, the high mortality rate and potential for mutations that could increase transmissibility give urgency to the search for direct, effective therapies. Well-designed and controlled clinical trials are needed, both for existing therapies and for prospective direct therapies. url: https://doi.org/10.1099/jmm.0.000565 doi: 10.1099/jmm.0.000565 id: cord-023372-ft8cp9op author: Rahman, Q. K. title: The Immunomodulatory Effect of Heat Shock Protein 70: Immunization with a DNA Construct Based on the Malarial Antigen Fused with a Fragment of HSP 70 Primes for a Th‐1 Type of Response date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Finding an appropriate adjuvant for human vaccination is crucial. Heat shock proteins (HSPs) act as adjuvants when coadministered with peptide antigens or given as fusion proteins. However, there is a potential risk of autoimmunity when using the complete molecules, because HSPs are evolutionary conserved. To overcome this, we first evaluated the adjuvant effect against two different antigens of a less‐conserved fraction of Plasmodium falciparum HSP70 (Pf70C) and compared it to the whole HSP70 molecule from Trypanosoma cruzi (TcHSP70). We found that Pf70C exhibited similar adjuvant properties as the whole molecule. We later evaluated the adjuvant potential of Pf70C against the malarial antigen EB200 in a chimeric DNA construct. No appreciable levels of EB200‐specific antibodies were detected in mice immunized only with the DNA constructs. However, DNA primed the immune system, because subsequent challenge with the corresponding recombinant fusion proteins elicited a strong Th‐1 antibody response. In contrast, no priming effect was observed for ex vivo IFN‐γ production but stimulation with the HSP‐chimeric fusion protein induced a stronger secretion of IFN‐γin vitro than other proteins used. These results indicate that the use of HSPs is promising in the design of new vaccines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169481/ doi: 10.1111/j.0300-9475.2004.01423aw.x id: cord-261380-xms5su6w author: Rahmani, Hamid title: Interferon β-1b in treatment of severe COVID-19: a randomized clinical trial date: 2020-08-24 words: 2770.0 sentences: 170.0 pages: flesch: 51.0 cache: ./cache/cord-261380-xms5su6w.txt txt: ./txt/cord-261380-xms5su6w.txt summary: Among an open-label, randomized clinical trial, adult patients (≥ 18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. According to the presence of this evidence, IFN β was considered as a promising option for the treatment of In this open-label, randomized clinical trial, efficacy and safety of IFN β-1b in the treatment of patients with severe CoVID-19 were assessed. This open-label, randomized clinical trial was designed to evaluate the efficacy and safety of IFN β-1b in the treatment of patients with CoVID19 Adult patients (≥ 18 years old) with positive PCR and clinical symptoms/signs of pneumonia (including dyspnea, cough and fever), peripheral oxygen saturation (SPO 2 ) ≤ 93 % in ambient air or arterial oxygen partial pressure to fractional inspired oxygen (PaO 2 /FiO 2 ) < 300 or SPO 2 /FiO 2 < 315 and lung involvement in chest imaging were included. abstract: In this study, efficacy and safety of interferon (IFN) β-1b in the treatment of patients with severe COVID-19 were evaluated. Among an open-label, randomized clinical trial, adult patients (≥ 18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN β-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7-10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality. Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group ([9(6-10) vs. 11(9-15) days respectively, p=0.002, HR= 2.30; 95% CI: 1.33-3.39]). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR= 3.09; 95% CI: 1.05-9.11, p=0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12). IFN β-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN β-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN β-1b. url: https://doi.org/10.1016/j.intimp.2020.106903 doi: 10.1016/j.intimp.2020.106903 id: cord-003382-v3w1wi5c author: Rahmatpanah, Farah title: Airway epithelial cells prime plasmacytoid dendritic cells to respond to pathogens via secretion of growth factors date: 2018-10-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Plasmacytoid dendritic cells (PDCs) are critical for defense against respiratory viruses because of their propensity to secrete high levels of type I interferons (IFN). The functions of PDCs in the lung can be influenced by airway epithelial cells. We examined the effect of human primary bronchial epithelial cells (PBECs) on PDC functions by performing RNA-sequencing of PDCs after co-culture with air liquid interface differentiated PBECs. Functional analysis revealed that PDCs co-cultured with PBECs displayed upregulation of type I IFN production and response genes. Upregulated transcripts included those encoding cytosolic sensors of DNA, ZBP-1,IRF-3, and NFkB as well as genes involved in amplification of the IFN response, such as IFNAR1, JAK/STAT, ISG15. In keeping with the RNA-seq data, we observe increased secretion of type I IFN and other cytokines in response to influenza in PDCs co-cultured with PBECs. The PDCs also primed Th1 responses in T cells. The enhanced response of PDCs co-cultured with PBECs was due to the action of growth factors, GMCSF, GCSF, and VEGF, which were secreted by PBECs on differentiation. These data highlight possible mechanisms to enhance the production of type-I IFN in the airways, which is critical for host defense against respiratory infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301110/ doi: 10.1038/s41385-018-0097-1 id: cord-347946-i6kx3n6m author: Raison, Charles L title: Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance date: 2016-09-15 words: 18693.0 sentences: 670.0 pages: flesch: 31.0 cache: ./cache/cord-347946-i6kx3n6m.txt txt: ./txt/cord-347946-i6kx3n6m.txt summary: Like sickness behavior, depression in response to immune activation aided in host defense both directly (ie, raised body temperature and energy conservation behaviors) and indirectly (social avoidance, energy conservation, and hypervigilance; Raison and Miller, pathogenhost defense theory of depression [PATHOS-D]) Adaptive explanations for associations between MDD and altered immune functioning are not considered (frequent unexamined assumption of researchers working on proximal mechanisms) Toll-like receptor (TLR) mRNA and protein have been reported to be elevated in both the periphery and CNS of individuals with MDD (Hung et al, 2014 (Hung et al, , 2015 Keri et al, 2014; van Dooren et al, 2016) , with some evidence suggesting that successful pharmaco-or psychotherapy reduces peripheral TLR activity (Keri et al, 2014; Hung et al, 2015) . abstract: Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression including its environmental and genetic risk factors, its association with the acute phase response and its age of onset and female preponderance appear to have evolved from human interactions with pathogens in the microbial world. Approaching the relationship between inflammation and depression from this evolutionary perspective yields a number of insights that may reveal important clues regarding the origin and epidemiology of the disorder as well as the persistence of its risk alleles in the modern human genome. url: https://www.ncbi.nlm.nih.gov/pubmed/27629366/ doi: 10.1038/npp.2016.194 id: cord-103625-p55ew8w7 author: Ramana, Chilakamarti V. title: Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses date: 2020-08-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Respiratory virus infection is one of the leading causes of death in the world. Activation of the Jak-Stat pathway by Interferon-alpha/beta (IFN-α/β) in lung epithelial cells is critical for innate immunity to respiratory viruses. Genetic and biochemical studies have shown that transcriptional regulation by IFN-α/β required the formation of Interferon-stimulated gene factor-3 (ISGF-3) complex consisting of Stat1, Stat2, and Irf9 transcription factors. Furthermore, IFN α/β receptor activates multiple signal transduction pathways in parallel to the Jak-Stat pathway and induces several transcription factors at mRNA levels resulting in the secondary and tertiary rounds of transcription. Transcriptional factor profiling in the transcriptome and RNA analysis revealed that Early growth response-1 (Egr-1) was rapidly induced by IFN-α/β and Toll-like receptor (TLR) ligands in multiple cell types. Studies in mutant cell lines lacking components of the ISGF-3 complex revealed that IFN-β induction of Egr-1 was independent of Stat1, Stat2, or Irf9. Activation of the Mek/Erk-1/2 pathway was implicated in the rapid induction of Egr-1 by IFN-β in serum-starved mouse lung epithelial cells. Interrogation of multiple microarray datasets revealed that respiratory viruses including coronaviruses regulated Egr-1 expression in human lung cell lines. Furthermore, Egr-1 inducible genes including transcription factors, mediators of cell growth, and chemokines were differentially regulated in the human lung cell lines after coronavirus infection, and in the lung biopsies of COVID-19 patients. Rapid induction by interferons, TLR ligands, and respiratory viruses suggests a critical role for Egr-1 in antiviral response and inflammation with potential implications for human health and disease. url: https://doi.org/10.1101/2020.08.14.244897 doi: 10.1101/2020.08.14.244897 id: cord-023402-8qfmo6rq author: Reinholdt, J. title: Pneumococcal IgA1 Protease Activity Interferes with Opsonophagocytosis of Streptococcus Pneumoniae Mediated by Serotype‐Specific Human Monoclonal IgA1 Antibodies date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bacteria‐specific IgA antibodies are efficient opsonins for neutrophils and mononuclear phagocytes, provided that the phagocytes express the Fca receptor (CD89). Expression of CD89 can be stimulated by inflammatory cytokines, activated complement factors and certain microbial components. In one study, unstimulated phagocytes were able to ingest IgA antibody‐treated pneumococci, but only in the presence of complement, which was found to be activated by the IgA antibodies along the alternative pathway. Pneumococci produce IgA1 protease that cleaves human IgA1, but not IgA2, molecules in the hinge region. This leaves IgA1 as Fabα (monovalent) deprived of Fcα which contains the docking site for CD89. IgA1 is the vastly predominant subclass of IgA in the upper airways and circulation of humans. Aims: To examine the effects of IgA1 protease activity and complement on phagocytosis of IgA antibody‐coated pneumococci by an unstimulated human phagocytic cell line (hl60). Materials and methods: IgA1 and IgA2 monoclonal antibodies to serotype 4 pneumococcal capsular polysaccharide (ps) were generated by heterohybridoma technique involving B cells from human vaccinees. Isogenic serotype 4 pneumococci with and without IgA1 protease activity, respectively, were obtained after inactivation of the iga gene of the TIGR4 strain. Opsonophagocytosis was quantitated using the assay described by Romero‐Steiner et al. Based on enumeration of surviving bacteria by culture. The integrity of IgA molecules was examined by western blotting. Results: Both IgA1 and IgA2 antibody to type‐4 polysaccharide‐induced phagocytosis of IgA1 protease‐deficient type‐4 pneumococci equally well in the absence as in the presence of complement. Iga1 antibody to type‐4 polysaccharide displayed a fourfold higher opsonophagocytosis titer against IgA1 protease deficient compared to homologous wildtype target bacteria. A similar effect of IgA1 protease activity of the target bacteria was not observed in a parallel experiment where IgA2 antibody to type‐4 polysaccharide served as opsonin. IgA1 antibody extracted from IgA1 protease‐producing target bacteria was almost exclusively in the form of Fabα. Conversely, IgA1 from protease‐deficient bacteria and IgA2 from both types of bacteria were intact. Conclusions: These results indicate that the IgA1 protease activity of S. neumoniae may help the bacteria escape IgA1 antibody‐mediated opsonophagocytosis. Besides, in these experiments, IgA‐mediated opsonophagocytosis was independent of complement. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169534/ doi: 10.1111/j.0300-9475.2004.01423t.x id: cord-268419-j90daoiq author: Resende, Lucilene Aparecida title: Cytokine and nitric oxide patterns in dogs immunized with LBSap vaccine, before and after experimental challenge with Leishmania chagasi plus saliva of Lutzomyia longipalpis date: 2013-12-06 words: 7182.0 sentences: 349.0 pages: flesch: 53.0 cache: ./cache/cord-268419-j90daoiq.txt txt: ./txt/cord-268419-j90daoiq.txt summary: chagasi challenge infection, PBMCs from LBSap vaccinated dogs produced more IL-12, IFN-γ and concomitant nitric oxide (NO) when stimulated with Leishmania antigens as compared to PBMCs from respective control groups (saponin, LBtreated, or non-treated control dogs). chagasi challenge infection, PBMCs from LBSap vaccinated dogs produced more IL-12, IFN-␥ and concomitant nitric oxide (NO) when stimulated with Leishmania antigens as compared to PBMCs from respective control groups (saponin, LB-treated, or non-treated control dogs). Thus, the profile of different cytokines (IL-4, IL-10, TGF-␤, IL-12, IFN-␥, and tumor necrosis factor [TNF]-␣) and nitric oxide (NO) in supernatants of peripheral blood mononuclear cell (PBMC) cultures were evaluated before the first immunization (T 0 ), 15 days after completion of the vaccine protocol (T 3 ), and at time points 90 (T 90 ) and 885 (T 885 ) days after experimental L. abstract: In the studies presented here, dogs were vaccinated against Leishmania (Leishmania) chagasi challenge infection using a preparation of Leishmania braziliensis promastigote proteins and saponin as adjuvant (LBSap). Vaccination with LBSap induced a prominent type 1 immune response that was characterized by increased levels of interleukin (IL-) 12 and interferon gamma (IFN-γ) production by peripheral blood mononuclear cells (PBMC) upon stimulation with soluble vaccine antigen. Importantly, results showed that this type of responsiveness was sustained after challenge infection; at day 90 and 885 after L. chagasi challenge infection, PBMCs from LBSap vaccinated dogs produced more IL-12, IFN-γ and concomitant nitric oxide (NO) when stimulated with Leishmania antigens as compared to PBMCs from respective control groups (saponin, LB- treated, or non-treated control dogs). Moreover, transforming growth factor (TGF)-β decreased in the supernatant of SLcA-stimulated PBMCs in the LBSap group at 90 days. Bone marrow parasitological analysis revealed decreased frequency of parasitism in the presence of vaccine antigen. It is concluded that vaccination of dogs with LBSap vaccine induced a long-lasting type 1 immune response against L. chagasi challenge infection. url: https://www.ncbi.nlm.nih.gov/pubmed/24129068/ doi: 10.1016/j.vetpar.2013.09.011 id: cord-277409-q5wx313k author: Resende, Lucilene Aparecida title: Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge date: 2016-08-24 words: 7939.0 sentences: 372.0 pages: flesch: 46.0 cache: ./cache/cord-277409-q5wx313k.txt txt: ./txt/cord-277409-q5wx313k.txt summary: Additionally, LbSap has been shown to induce a prominent pro-inflammatory immune response characterized by increased levels of both IL-12 and IFN-γ and decreased levels of TGF-β by peripheral blood mononuclear cells (PBMCs), which were associated with parasite control in dogs [26] . Previous studies of dogs using the "LbSapSal" vaccine displayed higher counts of circulating and Leishmania-specific CD8 + T cells in addition to high nitric oxide (NO) production [22] and reduction of splenic parasite load [27] . chagasi-challenge (T 90) demonstrated that "LbSapSal" group showed a significant increase of TNF-α levels (P<0.05) upon VSA-stimulation as compared to "Sal" and "LbSal" groups ( Fig 1A, middle panel) . The results observed at the post-vaccination period (T 3rd ) demonstrated that the "LbSal" group showed a significant reduction in the IL-10 levels (P<0.05) upon VSA-stimulation as compared to the "Sal" group ( Fig 2B, middle panel) . abstract: Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the “LbSapSal” vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T(0)), during the post-vaccination protocol (T(3rd)) and after early (T(90)) and late (T(885)) times following L. chagasi-challenge. Our major data indicated that immunization with “LbSapSal” is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after “LbSapSal” immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the “LbSapSal” vaccination is a potential tool to control the Leishmania chagasi infection. url: https://www.ncbi.nlm.nih.gov/pubmed/27556586/ doi: 10.1371/journal.pone.0161169 id: cord-012497-n5pu1yeu author: Rogers, Meredith C. title: STAT2 Limits Host Species Specificity of Human Metapneumovirus date: 2020-07-04 words: 6400.0 sentences: 333.0 pages: flesch: 53.0 cache: ./cache/cord-012497-n5pu1yeu.txt txt: ./txt/cord-012497-n5pu1yeu.txt summary: Finally, we sought to understand the in vivo role of STAT2 by infecting hSTAT2 knock-in mice with HMPV, and found that mice had increased weight loss, inhibition of type I interferon signaling, and a Th2-polarized cytokine profile compared to WT mice. Mouse models for HMPV have been developed, but mice are only semi-permissive for HMPV, requiring a high viral inoculum for productive in vivo infection ( [25] and unpublished observations), which may be due to species differences in the innate immune proteins antagonized by the virus. To better understand the global consequences of substituting human STAT2 into mice in vivo, we performed multiplex cytokine analysis on lung homogenates of HMPV-infected hSTAT2 KI and WT mice at day five after high-dose inoculation, as day five represents a time point that bridges innate and adaptive immunity. abstract: The host tropism of viral infection is determined by a variety of factors, from cell surface receptors to innate immune signaling. Many viruses encode proteins that interfere with host innate immune recognition in order to promote infection. STAT2 is divergent between species and therefore has a role in species restriction of some viruses. To understand the role of STAT2 in human metapneumovirus (HMPV) infection of human and murine tissues, we first infected STAT2(−/−) mice and found that HMPV could be serially passaged in STAT2(−/−), but not WT, mice. We then used in vitro methods to show that HMPV inhibits expression of both STAT1 and STAT2 in human and primate cells, but not in mouse cells. Transfection of the murine form of STAT2 into STAT2-deficient human cells conferred resistance to STAT2 inhibition. Finally, we sought to understand the in vivo role of STAT2 by infecting hSTAT2 knock-in mice with HMPV, and found that mice had increased weight loss, inhibition of type I interferon signaling, and a Th2-polarized cytokine profile compared to WT mice. These results indicate that STAT2 is a target of HMPV in human infection, while the murine version of STAT2 restricts tropism of HMPV for murine cells and tissue. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412095/ doi: 10.3390/v12070724 id: cord-341324-f9g9gitn author: Rojas, José M. title: Viral pathogen-induced mechanisms to antagonize mammalian interferon (IFN) signaling pathway date: 2020-10-21 words: 10837.0 sentences: 595.0 pages: flesch: 42.0 cache: ./cache/cord-341324-f9g9gitn.txt txt: ./txt/cord-341324-f9g9gitn.txt summary: This includes for instance cooperating in PRR recognition of viral PAMPs, stabilizing signaling complexes to improve their resistance to degradation, stopping virus entry, blocking viral capsid formation, impairing trafficking and budding of virions from the infected cells, but also modulating the IFN response to avoid the toxicity of these potent immune mediators. The phosphorylated STAT1/STAT2 heterodimer associates with interferon regulatory factor 9 (IRF9) to form the transcriptional factor complex ISGF3, which translocate to the nucleus and binds the IFN-response elements (ISRE) in ISG promoters leading to the expression of ISG products [36] (Fig. 2 The oligoadenylate synthetase (OAS)-latent RNase (RNase L) pathway is another IFN-inducible pathway that provides the cell with an effector mechanism upon recognition of viral dsRNA (reviewed in [44] ). abstract: Antiviral responses of interferons (IFNs) are crucial in the host immune response, playing a relevant role in controlling viralw infections. Three types of IFNs, type I (IFN-α, IFN-β), II (IFN-γ) and III (IFN-λ), are classified according to their receptor usage, mode of induction, biological activity and amino acid sequence. Here, we provide a comprehensive review of type I IFN responses and different mechanisms that viruses employ to circumvent this response. In the first part, we will give an overview of the different induction and signaling cascades induced in the cell by IFN-I after virus encounter. Next, highlights of some of the mechanisms used by viruses to counteract the IFN induction will be described. And finally, we will address different mechanism used by viruses to interference with the IFN signaling cascade and the blockade of IFN induced antiviral activities. url: https://www.ncbi.nlm.nih.gov/pubmed/33084946/ doi: 10.1007/s00018-020-03671-z id: cord-339991-k8z6v2vx author: Rong, Q. title: Multiple mechanisms for HSV-1 induction of interferon α production by peripheral blood mononuclear cells date: 2003 words: 5571.0 sentences: 273.0 pages: flesch: 48.0 cache: ./cache/cord-339991-k8z6v2vx.txt txt: ./txt/cord-339991-k8z6v2vx.txt summary: UV-inactivated, infectious, and other forms of herpes simplex virus 1 (HSV-1) induced interferon (IFN) production by different routes in myeloid origin mononuclear cells (MOMC) (consisting predominantly of monocytes). Comparison of the activities of different strains of infectious HSV, UV-inactivated HSV, and a mutant HSV incapable of penetration (K T) [9] and results of treatment with a mannose receptor antagonist indicate that there are more than one mechanism for HSV induction of interferon in the MOMC origin cell populations. The greater response to UV-inactivated virus suggests that non-infectious virions and possibly HSV infected cell debris are the more potent activators of IFN α production and that replicating virus can limit the induction of interferon production as a means of escaping host protection. Interferons and the colony-stimulating factors IL-3 and GM-CSF enhance the ifn-alpha response in human blood leucocytes induced by herpes simplex virus abstract: UV-inactivated, infectious, and other forms of herpes simplex virus 1 (HSV-1) induced interferon (IFN) production by different routes in myeloid origin mononuclear cells (MOMC) (consisting predominantly of monocytes). GM-CSF activated the MOMC (G-MOMC) to produce greater amounts of interferon while differentiation to DC, by the addition of granulocyte macrophage colony stimulating factor (GM-CSF) and calcium ionophore (GA-MOMC), reduced the levels of interferon production upon challenge with some HSV strains. UV-inactivated virus induced more interferon than infectious virus. L-fucose, an antagonist of the mannose receptor, inhibited the induction of IFN-α by UV-inactivated virus and gB(−) virus (defective in penetration) in MOMC and GA-MOMC but not G-MOMC. L-fucose had little effect on interferon induction by infectious HSV-1. The insensitivity of the G-MOMC to fucose inhibition distinguishes these interferon producing cells from the pDC2 cells previously described as natural interferon producing cells. The mannose receptor appears to be involved in the response to non-infectious forms of HSV but infectious virus appears to use a different pathway. These studies suggest that non-infectious virions and HSV infected cell debris effectively stimulate monocytes and pre-dendritic cells to produce IFN-α to initiate host protection against HSV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/12556996/ doi: 10.1007/s00705-002-0912-5 id: cord-340422-8f5xe4zc author: Rowland, R. R. R. title: Inhibition of porcine reproductive and respiratory syndrome virus by interferon-gamma and recovery of virus replication with 2-aminopurine date: 2001 words: 4715.0 sentences: 283.0 pages: flesch: 50.0 cache: ./cache/cord-340422-8f5xe4zc.txt txt: ./txt/cord-340422-8f5xe4zc.txt summary: Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to a group of RNA viruses that establish persistent infections. IFN-γ mRNA expression was observed in the lymph nodes and lungs of pigs infected with wild-type PRRSV strain SDSU-23983. The purpose of this study was to evaluate the production of IFN-␥ in pigs following infection with PRRSV and to characterize the mechanism of IFN-␥ action following infection of MARC-145 cells with wild-type and culture adapted PRRSV isolates. The results show that IFN-␥ efficiently inhibits PRRSV replication in MARC-145 cells, and at least part of the antiviral activity may be through PKR. IFN-␥ mRNA expression was detected in the lymph nodes from two of the 3 pigs infected with the wild-type P6 virus (Fig. 1) . Consistent with other reports describing the presence of cell-mediated immunity during PRRSV infection [4, 31] , we observed IFN-␥ mRNA expression in lymph nodes and lungs of PRRSV-infected pigs (Fig. 1) . IFN gamma inhibits porcine reproductive and respiratory syndrome virus replication in macrophages abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to a group of RNA viruses that establish persistent infections. A proposed strategy for evading immunity during persistent PRRSV infection is by preventing the induction of IFN activity in pigs and/or by blocking the activation of antiviral proteins in permissive cells. IFN-γ mRNA expression was observed in the lymph nodes and lungs of pigs infected with wild-type PRRSV strain SDSU-23983. Pretreatment of MARC-145 cells with IFN-γ inhibited wild-type (SDSU-23983 P6) and culture-adapted (SDSU-23983 P136) PRRS viruses in a dose-dependent manner and at relatively low concentrations. The effect of IFN-γ on virus replication included reductions in the number of infected cells, virus yield, and RNA content in single cells. Virus replication was partially restored by the addition of 2-aminopurine (2-AP), an inhibitor of dsRNA inducible protein kinase (PKR). The addition of 2-AP also restored the viral RNA content per cell to near normal levels, suggesting that inhibition of viral RNA synthesis was through PKR. The principal difference between P6 and P136 isolates was the recovery of P136 replication with lower concentrations of 2-AP. Immunostaining with anti-PKR antibody showed a redistribution of PKR from the cytoplasm into nucleoli of infected cells. url: https://www.ncbi.nlm.nih.gov/pubmed/11338389/ doi: 10.1007/s007050170161 id: cord-275413-e2rhioty author: Rowland, Raymond R.R. title: The interaction between PRRSV and the late gestation pig fetus date: 2010-09-09 words: 6183.0 sentences: 344.0 pages: flesch: 50.0 cache: ./cache/cord-275413-e2rhioty.txt txt: ./txt/cord-275413-e2rhioty.txt summary: The purpose of this study was to characterize the interaction between PRRSV and the pig fetus by (1) identifying sites of virus replication, (2) measuring immune and inflammatory cytokines in different compartments, and (3) evaluating the response of lymph nodes. Maternal, accessory and fetal tissues were collected and stored in formalin for histological staining and immunohistochemistry (IHC), or storage in RNAlater (Ambion) for RT-PCR of cytokine mRNAs. PRRSV-specific antibody was measured in sera using the HerdCheck ® PRRS ELISA (IDEXX) and performed by personnel at Kansas State University Veterinary Diagnostic Laboratory. As shown in Fig. 4A , IFN-␥ and TNF-␣ PCR products were not detected in lung, lymph node or placenta from the non-infected fetuses. To determine if cytokine gene expression was the direct result of PRRSV infection, RT-PCR for IFN-␥ and TNF-␣ was performed on the same tissues from fetuses of infected dam no. abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta during late gestation and productively infects the fetus. Virus replication and cytokine responses were measured in tissues of fetuses recovered at 109–112 days of gestation, just prior to parturition. At the time of recovery, gross anatomical abnormalities were evident in both infected and non-infected fetuses from the infected dams. Virus isolation and immunohistochemistry identified the thymus as the primary site of virus replication. Steady state RT-PCR amplification of inflammatory, Th1 and Th2 cytokines, showed elevated IFN-γ and TNF-α mRNAs in tissues from infected fetuses, which corresponded to elevated cytokine proteins in serum but not amniotic fluid. Further evidence for induction of immunity was found in the hyperplastic response of lymph nodes, which included the development of germinal centers occupied CDw75+ B cells. Collectively, these data support the notion that the immunocompetent fetus is capable of initiating an antiviral response, which is compartmentalized within the infected fetus. Furthermore, fetal pathology may not be a direct result of virus replication in the fetus. url: https://www.ncbi.nlm.nih.gov/pubmed/20832434/ doi: 10.1016/j.virusres.2010.09.001 id: cord-270326-fzsczb8m author: Rubio, Nazario title: Demonstration of the presence of a specific interferon-γ receptor on murine astrocyte cell surface date: 1991-12-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Interferon gamma (IFN-γ) is a pleiotropic lymphokine produced by T-lymphocytes which acts as a soluble mediator in immunological reactions. In addition to several immune target cells, such as monocytes and macrophages, it acts on the principal glial population, the astrocytes, inducing Ia antigen expression. We have developed a binding assay for 125I-labeled recombinant murine IFN-γ, and show that, using this assay, IFN-γ interacts with a single specific receptor on the murine astrocyte cell membrane. The binding is specific and saturable and it takes place with a K d = 1.64 × 10−9 M, with 11,100 receptor molecules per astrocytic cell. The binding shows, as for macrophages, species specificity. Using an immune assay including rabbit antibodies to IFN-γ and 125I-labeled protein A, we have demonstrated an internalization of the ligand. This is an energy-dependent process, as around 50% of the bound IFN-γ is endocytosed after 4 h at 37°C when cultures are maintained in complete culture medium. url: https://www.sciencedirect.com/science/article/pii/0165572891901665 doi: 10.1016/0165-5728(91)90166-5 id: cord-023429-x52gbklw author: Ruseva, M. title: Mannan‐Binding Lectin Inhibits Humoural Responses date: 2008-06-28 words: 16880.0 sentences: 871.0 pages: flesch: 46.0 cache: ./cache/cord-023429-x52gbklw.txt txt: ./txt/cord-023429-x52gbklw.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Chronic hepatitis B virus (HBV) infection affects about 200–400 million people worldwide and represents one of the leading causes for liver cirrhosis and hepatocellular carcinoma. Control over the HBV infection is achieved mainly by vaccination with Hepatitis B surface antigen (HBsAg). HBsAg contains N‐linked glycosylation side and is recognized by both MBL‐A and MBL‐C in a Ca‐dependent manner. HbsAg–MBL complexes activate complement and may thus affect humoural immunity. To investigate the role of MBL in humoural responses to HBsAg, we immununized mice that lack both MBL‐A and MBL‐C proteins with soluble HBsAg. It has been shown that deficiencies in other complement components like C1q, C4 and C3 result in decreased antibody responses. However, MBL double KO animals mounted dramatically increased humoural responses. After priming, MBL double KOs mounted HbsAg‐specific IgM responses, which were threefold higher than WT controls. After boosting the HBsAg, total IgG was 10‐fold higher in MBL KO than in WT control animals. Similar to the response to HbsAg, other glycosylated soluble antigens (e.g. invertase) induced better humoural responses in MBL double KO animals, suggesting that MBL plays an important role in a negative feedback regulation of adaptive immunity. Reconstitution experiments with rMBL partially rescued the KO phenotype. We propose that the clearance of glycoprotein antigens in MBL KO is handled differently from the WT, resulting in better stimulation of humoural responses. Alternatively, glycoprotein‐Ag‐MBL‐rich complexes inhibit B‐cell responsiveness via putative MBL receptors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169581/ doi: 10.1111/j.0300-9475.2004.01423an.x id: cord-263862-zzys31e9 author: Ryan, Elizabeth J. title: The Canarypox-virus vaccine vector ALVAC triggers the release of IFN-γ by Natural Killer (NK) cells enhancing Th1 polarization date: 2007-04-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We investigated the mechanism by which ALVAC activates innate immunity. Combining ALVAC with protein antigens significantly augmented antigen-specific IgG2a responses; this was dependent on the presence of bioactive interferon (IFN)-γ. Immuno-depletion of NK cells prior to ALVAC immunisation abrogated IFN-γ production indicating that they are the main cellular source of early IFN-γ in vivo. Murine bone-marrow derived dendritic cells (BMDCs) cultured in the presence of ALVAC secreted high levels of the chemokines CXCL10 and CCL2 and up-regulated expression of the maturation markers CD40, CD80 and CD86. Therefore, we conclude that ALVAC acts as an adjuvant through a mechanism requiring NK cell derived IFN-γ, DC activation and chemokine secretion. url: https://www.sciencedirect.com/science/article/pii/S0264410X06013880 doi: 10.1016/j.vaccine.2006.12.048 id: cord-023425-3sjsogvq author: Røntved, C. M. title: Do High and Low Tumour Necrosis Factor‐α Responders Exist in Dairy Cows? date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A whole blood stimulation assay with Escherichia coli (O111:B4) endotoxin was established to measure the capacity of dairy cows to produce the proinflammatory cytokine tumour necrosis factor‐α (TNF‐α) ex vivo. Initially, a time‐ and dose‐dependent study was carried out to find the optimal stimulation conditions for the TNF‐α response. The TNF‐α response peaked between 3 and 4 h at 38.5 °C. A dose in the range of 5–10 g of E. coli lipopolysaccharide (LPS)/ml whole blood was found to give the maximum TNF‐α response. Thirty‐eight Danish–Holstein dairy cows were investigated for their TNF‐α responsiveness ex vivo in the periparturient period. Heparin‐stabilized blood samples were collected seven times over a period of 4 months (weeks −3, −1, 2, 3, 5, 9 and 13 around calving) and stimulated with 5 g/ml of E. coli LPS. Indeed, fluctuations in the TNF‐α responsiveness occurred over time. Moreover, the mean TNF‐α responsiveness of 38 cows was found to be significantly increased (P < 0.001) in the weeks close to calving. However, in the more stabile physiological periods, some cows had a consistently low TNF‐α response, whereas others had high a TNF‐α response. We are currently investigating whether high and low TNF‐α responders to E. coli LPS also exist in dairy cows in vivo. Moreover, the importance of TNF‐α responsiveness ex vivo to dairy cows' susceptibility and clinical response to experimental E. coli infections in the udder is being investigated. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169577/ doi: 10.1111/j.0300-9475.2004.01423v.x id: cord-286072-kgpvdb42 author: Sa Ribero, Margarida title: Interplay between SARS-CoV-2 and the type I interferon response date: 2020-07-29 words: 7026.0 sentences: 360.0 pages: flesch: 43.0 cache: ./cache/cord-286072-kgpvdb42.txt txt: ./txt/cord-286072-kgpvdb42.txt summary: While awaiting the results of the many clinical trials that are evaluating the efficacy of IFN-I alone or in combination with antiviral molecules, we discuss the potential benefits of a well-timed IFN-I treatment and propose strategies to boost pDC-mediated IFN responses during the early stages of viral infection. IFN, interferon; IFNAR, interferon alpha and beta receptor; IκB, inhibitor of nuclear factor κB; IKKε, IκB kinase-ε; IRF, IFN regulatory factor; ISG, IFN-stimulated gene; JAK, Janus kinase; M, membrane; MAVS, mitochondrial antiviral signaling protein; MDA5, melanoma differentiation-associated gene 5; N, nucleocapsid; Nsp, nonstructural protein; ORF, open reading frame; P, phosphate; PLP, papain-like protease; RIG-I, retinoic acid-inducible gene 1; SARS-CoV, severe acute respiratory syndrome coronavirus; STAT, signal transducer and activator of transcription; TANK, TRAF family member associated NF-κB activator; TBK1, TANK-binding kinase 1; TRAF3, tumor necrosis factor receptor-associated factor 3; TYK2, tyrosine kinase 2. abstract: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. An unbalanced immune response, characterized by a weak production of type I interferons (IFN-Is) and an exacerbated release of proinflammatory cytokines, contributes to the severe forms of the disease. SARS-CoV-2 is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2003 and 2013, respectively. Although IFN treatment gave some encouraging results against SARS-CoV and MERS-CoV in animal models, its potential as a therapeutic against COVID-19 awaits validation. Here, we describe our current knowledge of the complex interplay between SARS-CoV-2 infection and the IFN system, highlighting some of the gaps that need to be filled for a better understanding of the underlying molecular mechanisms. In addition to the conserved IFN evasion strategies that are likely shared with SARS-CoV and MERS-CoV, novel counteraction mechanisms are being discovered in SARS-CoV-2–infected cells. Since the last coronavirus epidemic, we have made considerable progress in understanding the IFN-I response, including its spatiotemporal regulation and the prominent role of plasmacytoid dendritic cells (pDCs), which are the main IFN-I–producing cells. While awaiting the results of the many clinical trials that are evaluating the efficacy of IFN-I alone or in combination with antiviral molecules, we discuss the potential benefits of a well-timed IFN-I treatment and propose strategies to boost pDC-mediated IFN responses during the early stages of viral infection. url: https://doi.org/10.1371/journal.ppat.1008737 doi: 10.1371/journal.ppat.1008737 id: cord-313684-61hkogdh author: Samaddar, Arghadip title: Pathophysiology and Potential Therapeutic Candidates for COVID-19: A Poorly Understood Arena date: 2020-09-17 words: 11700.0 sentences: 585.0 pages: flesch: 42.0 cache: ./cache/cord-313684-61hkogdh.txt txt: ./txt/cord-313684-61hkogdh.txt summary: Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the Wuhan City of China in December 2019 and evolved into a global pandemic. These include antivirals (remdesivir, lopinavir/ritonavir, umifenovir, and favipiravir), interferon, antimalarials (chloroquine/hydroxychloroquine), antiparasitic drugs (ivermectin and nitazoxanide), biologics (monoclonal antibodies and interleukin receptor antagonist), cellular therapies (mesenchymal stem cells and natural killer cells), convalescent plasma, and cytokine adsorber. Though several observational studies have claimed many of these agents to be effective based on their in vitro activities and extrapolated evidence from SARS and Middle East respiratory syndrome (MERS) epidemics, the currently available data remains inconclusive because of ill-defined patient selection criteria, small sample size, lack of concurrent controls, and use of intermediary outcomes instead of patient-relevant outcomes. abstract: Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the Wuhan City of China in December 2019 and evolved into a global pandemic. To date, there are no proven drugs or vaccines against this virus. Hence, the situation demands an urgent need to explore all potential therapeutic strategies that can be made available to prevent the disease progression and improve patient outcomes. In absence of clinically proven treatment guidelines, several repurposed drugs and investigational agents are currently being evaluated in clinical trials for their probable benefits in the treatment of COVID-19. These include antivirals (remdesivir, lopinavir/ritonavir, umifenovir, and favipiravir), interferon, antimalarials (chloroquine/hydroxychloroquine), antiparasitic drugs (ivermectin and nitazoxanide), biologics (monoclonal antibodies and interleukin receptor antagonist), cellular therapies (mesenchymal stem cells and natural killer cells), convalescent plasma, and cytokine adsorber. Though several observational studies have claimed many of these agents to be effective based on their in vitro activities and extrapolated evidence from SARS and Middle East respiratory syndrome (MERS) epidemics, the currently available data remains inconclusive because of ill-defined patient selection criteria, small sample size, lack of concurrent controls, and use of intermediary outcomes instead of patient-relevant outcomes. Moreover, there is a need to clearly define the patient populations who warrant therapy and also the timing of initiation of treatment. Understanding the disease pathology responsible for the clinical manifestations of COVID-19 is imperative to identify the potential targets for drug development. This review explains the pathophysiology of COVID-19 and summarizes the potential treatment candidates, which can provide guidance in developing effective therapeutic strategies. url: https://doi.org/10.3389/fphar.2020.585888 doi: 10.3389/fphar.2020.585888 id: cord-265697-bbvlowyo author: Sang, Eric R. title: Integrate structural analysis, isoform diversity, and interferon-inductive propensity of ACE2 to predict SARS-CoV2 susceptibility in vertebrates date: 2020-08-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The current new coronavirus disease (COVID-19) has caused globally near 0.4/6 million confirmed deaths/infected cases across more than 200 countries. As the etiological coronavirus (a.k.a. SARS-CoV2) may putatively have a bat origin, our understanding about its intermediate reservoir between bats and humans, especially its tropism in wild and domestic animals are mostly unknown. This constitutes major concerns in public health for the current pandemics and potential zoonosis. Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad potential of SARS-CoV2 susceptibility in wild and particularly domestic animals. Through integration of key immunogenetic factors, including the existence of S-binding-void ACE2 isoforms and the disparity of ACE2 expression upon early innate immune response, we further refine the SARS-CoV2 susceptibility prediction to fit recent experimental validation. In addition to showing a broad susceptibility potential across mammalian species based on structural analysis, our results also reveal that domestic animals including dogs, pigs, cattle and goats may evolve ACE2-related immunogenetic diversity to restrict SARS-CoV2 infections. Thus, we propose that domestic animals may be unlikely to play a role as amplifying hosts unless the virus has further species-specific adaptation. Findings may relieve relevant public concerns regarding COVID-19-like risk in domestic animals, highlight virus-host coevolution, and evoke disease intervention through targeting ACE2 molecular diversity and interferon optimization. url: https://www.ncbi.nlm.nih.gov/pubmed/32904785/ doi: 10.1016/j.heliyon.2020.e04818 id: cord-315483-l6dm82pp author: Santhakumar, Diwakar title: Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses date: 2018-05-01 words: 10776.0 sentences: 579.0 pages: flesch: 47.0 cache: ./cache/cord-315483-l6dm82pp.txt txt: ./txt/cord-315483-l6dm82pp.txt summary: To confirm the sequence of the cDNA and to identify the genomic structure of the identified IFIT gene, the transcript was amplified from RNA extracted from NDV-infected CEFs. Complete sequence analysis of the gene revealed an open reading frame (ORF) of 1440 bps (479 amino acids excluding stop codon) with high sequence identity (48% and 67%) with the human and duck IFIT5 proteins, respectively ( Supplementary Fig. 1B) . The levels of chIFN-β gene induction was proportional to the NDV replication (Fig. 2D) , therefore, it can be inferred that the virus-induced expression of chicken IFIT5 is IFN-dependent and that chIFIT5 is an early-ISG with capacity to modulate initial steps of virus life cycle. To compare anti-viral effects of chIFIT5 (only IFIT gene identified in chickens so far) with its orthologous and homologous human proteins, huIFIT1, huIFIT2, huIFIT3 and huIFIT5 were expressed in chicken cells and antiviral affect was monitored (Fig. 5A ). abstract: The intracellular actions of interferon (IFN)-regulated proteins, including IFN-induced proteins with tetratricopeptide repeats (IFITs), attribute a major component of the protective antiviral host defense. Here we applied genomics approaches to annotate the chicken IFIT locus and currently identified a single IFIT (chIFIT5) gene. The profound transcriptional level of this effector of innate immunity was mapped within its unique cis-acting elements. This highly virus- and IFN-responsive chIFIT5 protein interacted with negative sense viral RNA structures that carried a triphosphate group on its 5′ terminus (ppp-RNA). This interaction reduced the replication of RNA viruses in lentivirus-mediated IFIT5-stable chicken fibroblasts whereas CRISPR/Cas9-edited chIFIT5 gene knockout fibroblasts supported the replication of RNA viruses. Finally, we generated mosaic transgenic chicken embryos stably expressing chIFIT5 protein or knocked-down for endogenous chIFIT5 gene. Replication kinetics of RNA viruses in these transgenic chicken embryos demonstrated the antiviral potential of chIFIT5 in ovo. Taken together, these findings propose that IFIT5 specifically antagonize RNA viruses by sequestering viral nucleic acids in chickens, which are unique in innate immune sensing and responses to viruses of both poultry and human health significance. url: https://www.ncbi.nlm.nih.gov/pubmed/29717152/ doi: 10.1038/s41598-018-24905-y id: cord-317499-mxt7stat author: Saraya, Takeshi title: Epidemiology of virus-induced asthma exacerbations: with special reference to the role of human rhinovirus date: 2014-05-26 words: 5655.0 sentences: 300.0 pages: flesch: 43.0 cache: ./cache/cord-317499-mxt7stat.txt txt: ./txt/cord-317499-mxt7stat.txt summary: Table 1 shows the frequency of HRV infection in various adult respiratory diseases such as exacerbation of asthma (Nicholson et al., 1993; Atmar et al., 1998; Tan et al., 2003) , common cold (Makela et al., 1998; van Gageldonk-Lafeber et al., 2005) , exacerbation of COPD (Seemungal et al., 2001; Rohde et al., 2003; Tan et al., 2003; Beckham et al., 2005; Papi et al., 2006; Hutchinson et al., 2007; Ko et al., 2007; McManus et al., 2008; Kherad et al., 2010; Dimopoulos et al., 2012; Perotin et al., 2013) , community acquired pneumonia (Jennings et al., 2008; Johnstone et al., 2008; Johansson et al., 2010; Lieberman et al., 2010; Fry et al., 2011; Wootton et al., 2011; Luchsinger et al., 2013; Takahashi et al., 2013; Huijskens et al., 2014) , exacerbation of idiopathic pulmonary fibrosis (Wootton et al., 2011) , and asymptomatic infection (Fry et al., 2011) . abstract: Viral respiratory infections may be associated with the virus-induced asthma in adults as well as children. Particularly, human rhinovirus is strongly suggested a major candidate for the associations of the virus-induced asthma. Thus, in this review, we reviewed and focused on the epidemiology, pathophysiology, and treatment of virus-induced asthma with special reference on human rhinovirus. Furthermore, we added our preliminary data regarding the clinical and virological findings in the present review. url: https://www.ncbi.nlm.nih.gov/pubmed/24904541/ doi: 10.3389/fmicb.2014.00226 id: cord-271250-ywb26cq6 author: Sarkar, Indranil title: Selection of adjuvants for vaccines targeting specific pathogens date: 2019-04-22 words: 11394.0 sentences: 542.0 pages: flesch: 39.0 cache: ./cache/cord-271250-ywb26cq6.txt txt: ./txt/cord-271250-ywb26cq6.txt summary: In-depth understanding of the role of adjuvants in activating the innate immune system, combined with systems vaccinology approaches, have led to the development of next-generation, novel adjuvants that can be used in vaccines against challenging pathogens and in specific target populations. Intact MyD88 signaling in each of the three types of APCs (DCs, macrophages and B cells) is essential for robust activity of TLR ligand-based vaccine adjuvants (PorB, a TLR2 ligand and CpG, a TLR9 ligand) such as induction of in vivo cytokine responses, germinal center (GC) formation and antibody production [49] . A combination adjuvant consisting of poly(I:C), a host defense peptide and PCEP when delivered intranasally transiently induces production of chemokines and cytokines in murine respiratory tissues, which promotes infiltration and activation of DCs, macrophages, and neutrophils to generate improved mucosal and systemic immune responses [55] . abstract: Introduction: Adjuvants form an integral component in most of the inactivated and subunit vaccine formulations. Careful and proper selection of adjuvants helps in promoting appropriate immune responses against target pathogens at both innate and adaptive levels such that protective immunity can be elicited. Areas covered: Herein, we describe the recent progress in our understanding of the mode of action of adjuvants that are licensed for use in human vaccines or in clinical or pre-clinical stages at both innate and adaptive levels. Different pathogens have distinct characteristics, which require the host to mount an appropriate immune response against them. Adjuvants can be selected to elicit a tailor-made immune response to specific pathogens based on their unique properties. Identification of biomarkers of adjuvanticity for several candidate vaccines using omics-based technologies can unravel the mechanism of action of modern and experimental adjuvants. Expert opinion: Adjuvant technology has been revolutionized over the last two decades. In-depth understanding of the role of adjuvants in activating the innate immune system, combined with systems vaccinology approaches, have led to the development of next-generation, novel adjuvants that can be used in vaccines against challenging pathogens and in specific target populations. url: https://www.ncbi.nlm.nih.gov/pubmed/31009255/ doi: 10.1080/14760584.2019.1604231 id: cord-337717-8hcujmuo author: Savarin, Carine title: IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils date: 2012-05-29 words: 6901.0 sentences: 372.0 pages: flesch: 44.0 cache: ./cache/cord-337717-8hcujmuo.txt txt: ./txt/cord-337717-8hcujmuo.txt summary: CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT) or IFN-γ deficient (GKO) memory CD4(+) T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade. RESULTS: Transfer of GKO memory CD4(+) T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4(+) T cells, despite similar virus control and demyelination. Overall these data confirm IFN-γ-mediated control of CNS neutrophil infiltration and suggested a protective role of IFN-γ during viral encephalitis, via inhibiting IL-17 effector function by either directly reducing Th17 cell expansion and/or CNS entry, or limiting GM-CSF production. Although GM-CSF expression is reduced by IFN-γ [27] , the data do not support a pathogenic role of GM-CSF in early mortality of JHMV-infected GKO recipients. abstract: BACKGROUND: The interplay between IFN-γ, IL-17 and neutrophils during CNS inflammatory disease is complex due to cross-regulatory factors affecting both positive and negative feedback loops. These interactions have hindered the ability to distinguish the relative contributions of neutrophils, Th1 and Th17 cell-derived effector molecules from secondary mediators to tissue damage and morbidity. METHODS: Encephalitis induced by a gliatropic murine coronavirus was used as a model to assess the direct contributions of neutrophils, IFN-γ and IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT) or IFN-γ deficient (GKO) memory CD4(+) T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade. RESULTS: Transfer of GKO memory CD4(+) T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4(+) T cells, despite similar virus control and demyelination. In contrast to recipients of WT CD4(+) T cells, extensive neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO CD4(+) T cells provided a model to directly assess their contribution(s) to disease. Recipients of WT CD4(+) T cells depleted of IFN-γ did not express IL-17 and were spared from mortality despite abundant CNS neutrophil infiltration, indicating that mortality was not mediated by excessive CNS neutrophil accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4(+) T cells from rapid mortality without diminishing neutrophils or reducing GM-CSF, associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co-transfer of WT and GKO CD4(+) T cells prolonged survival in an IFN-γ dependent manner, although IL-17 transcription was not reduced. CONCLUSIONS: These data demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-γ-deprived environment, independent of extensive neutrophil accumulation or GM-CSF upregulation. The results also suggest that IFN-γ overrides the detrimental IL-17 effector responses via a mechanism downstream of transcriptional regulation. url: https://doi.org/10.1186/1742-2094-9-104 doi: 10.1186/1742-2094-9-104 id: cord-007689-0vpp3xdl author: Schlee, M. title: Beyond Double-Stranded RNA-Type I IFN Induction by 3pRNA and Other Viral Nucleic Acids date: 2007 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Production of type I IFN is the key response to viral infection. Since the discovery of type I IFNs in 1957, long double-stranded RNA formed during replication of many viruses was thought to be responsible for type I IFN induction, and for decades double-stranded RNA-activated protein kinase (PKR) was thought to be the receptor. Recently, this picture has dramatically changed. It now became evident that not PKR but two members of the Toll-like receptor (TLR) family, TLR7 and TLR9, and two cytosolic helicases, RIG-I and MDA-5, are responsible for the majority of type I IFNs induced upon recognition of viral nucleic acids. In this review, we focus on the molecular mechanisms by which those innate immune receptors detect viral infection. Based on the recent progress in the field, we now know that TLR7, TLR9, and RIG-I do not require long double-stranded RNA for type I IFN induction. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120510/ doi: 10.1007/978-3-540-71329-6_11 id: cord-307598-p54p7enk author: Schlee, Martin title: Master sensors of pathogenic RNA – RIG-I like receptors date: 2013-07-01 words: 12853.0 sentences: 779.0 pages: flesch: 56.0 cache: ./cache/cord-307598-p54p7enk.txt txt: ./txt/cord-307598-p54p7enk.txt summary: Similar to TLRs, RIG-I and MDA5 induce type I IFN and chemokines (but no IL12) upon activation by viral but also bacterial RNA. Since type I IFN induction by this RNA required RNase L, the authors concluded that RNase L recognizes and processes viral mRNA into a MDA5 activating structure. Before 5 triphosphate was identified as the crucial RNA modification to induce RIG-I activation, Marques and colleagues observed that synthetic blunt ended dsRNA oligonucleotides can stimulate RIG-I ( Fig. 3 ) (Marques et al. (2010b) confirmed the requirement of a base paired 5 -ppp end of dsRNA for RIG-I activation and suggested that some arenaviruses and bunyaviruses use a prime and realign mechanism for genome synthesis, leading to 5 overhangs in order to evade RIG-I recognition (Marq et al. pneumophilae did not induce type I IFN in HEK293 cells, thus excluding RIG-I-mediated recognition of RNA polymerase-III transcripts in the host cell, as previously suggested (Chiu et al. abstract: Initiating the immune response to invading pathogens, the innate immune system is constituted of immune receptors (pattern recognition receptors, PRR) that sense microbe-associated molecular patterns (MAMPs). Detection of pathogens triggers intracellular defense mechanisms, such as the secretion of cytokines or chemokines to alarm neighboring cells and attract or activate immune cells. The innate immune response to viruses is mostly based on PRRs that detect the unusual structure, modification or location of viral nucleic acids. Most of the highly pathogenic and emerging viruses are RNA genome-based viruses, which can give rise to zoonotic and epidemic diseases or cause viral hemorrhagic fever. As viral RNA is located in the same compartment as host RNA, PRRs in the cytosol have to discriminate between viral and endogenous RNA by virtue of their structure or modification. This challenging task is taken on by the homologous cytosolic DExD/H-box family helicases RIG-I and MDA5, which control the innate immune response to most RNA viruses. This review focuses on the molecular basis for RIG-I like receptor (RLR) activation by synthetic and natural ligands and will discuss controversial ligand definitions. url: https://api.elsevier.com/content/article/pii/S0171298513001204 doi: 10.1016/j.imbio.2013.06.007 id: cord-312955-gs65c3fy author: Schreiber, Gideon title: The Role of Type I Interferons in the Pathogenesis and Treatment of COVID-19 date: 2020-09-30 words: 8418.0 sentences: 467.0 pages: flesch: 48.0 cache: ./cache/cord-312955-gs65c3fy.txt txt: ./txt/cord-312955-gs65c3fy.txt summary: Although SARS-CoV-2 inhibits the production of IFNβ and thus obstructs the innate immune response to this virus, it is sensitive to the antiviral activity of externally administrated IFN-Is. In this review I discuss the diverse modes of biological actions of IFN-Is and how these are related to biophysical parameters of IFN-I–receptor interaction and cell-type specificity in light of the large variety of binding affinities of the different IFN-I subtypes towards the common interferon receptor. Thereby, it inhibits the nuclear transport of phosphorylated STAT1, rendering cells refractory to IFN-Is. Another example of viral mechanisms that evolved to eliminate IFN-I functions in inducing innate immunity is given by the SARS corona virus, where both the production of IFNb and the IFN-I induced signaling are attenuated. This gene was found to preferentially cleave the ubiquitin-like modifier interferon-stimulated gene 15 (ISG15), FIGURE 4 | SARS-CoV-2 has multiple effects on the immune system, including inhibition of IFNb production, which results in ISGs not to be produced, CD4+ and CD8+ exhaustion and increased levels of pro-inflammatory proteins (TNFa, IL6, NF-kB). abstract: Type I interferons (IFN-I) were first discovered over 60 years ago in a classical experiment by Isaacs and Lindenman, who showed that IFN-Is possess antiviral activity. Later, it became one of the first approved protein drugs using heterologous protein expression systems, which allowed its large-scale production. It has been approved, and widely used in a pleiotropy of diseases, including multiple-sclerosis, hepatitis B and C, and some forms of cancer. Preliminary clinical data has supported its effectiveness against potential pandemic pathogens such as Ebola and SARS. Still, more efficient and specific drugs have taken its place in treating such diseases. The COVID-19 global pandemic has again lifted the status of IFN-Is to become one of the more promising drug candidates, with initial clinical trials showing promising results in reducing the severity and duration of the disease. Although SARS-CoV-2 inhibits the production of IFNβ and thus obstructs the innate immune response to this virus, it is sensitive to the antiviral activity of externally administrated IFN-Is. In this review I discuss the diverse modes of biological actions of IFN-Is and how these are related to biophysical parameters of IFN-I–receptor interaction and cell-type specificity in light of the large variety of binding affinities of the different IFN-I subtypes towards the common interferon receptor. Furthermore, I discuss how these may guide the optimized use IFN-Is in combatting COVID-19. url: https://doi.org/10.3389/fimmu.2020.595739 doi: 10.3389/fimmu.2020.595739 id: cord-299949-kmn53e2z author: Schultz, Kimberly L.W. title: Immune Responses to Viruses in the CNS date: 2016-05-09 words: 6946.0 sentences: 349.0 pages: flesch: 41.0 cache: ./cache/cord-299949-kmn53e2z.txt txt: ./txt/cord-299949-kmn53e2z.txt summary: For recovery from infection, the immune response in the central nervous system (CNS) must eliminate or control virus replication without destroying nonrenewable, essential cells. For recovery after virus infection of the central nervous system (CNS), the essential, nonrenewable nature of neurons requires a fine-tuned immune response that controls virus replication without damaging neuronal function. Detailed studies of immune responses to neurotropic viruses have included neuronal infections with rabies virus, flaviviruses, and alphaviruses, as well as infection of multiple cell types with natural mouse pathogens such as Theiler''s murine encephalomyelitis virus (TMEV), mouse hepatitis virus (MHV), and lymphocytic choriomeningitis virus (LCMV). Resident cells in the nervous system, including neurons, play an active role in the immune response (Schultz et al., 2014; O''Donnell et al., 2012; Chakraborty et al., 2010; Daffis et al., 2008a; Castorena et al., 2008; Daffis et al., 2007; Commonly used in mouse models of viral encephalitis. abstract: For recovery from infection, the immune response in the central nervous system (CNS) must eliminate or control virus replication without destroying nonrenewable, essential cells. Thus, upon intracellular virus detection, the infected cell must initiate clearance pathways without triggering neuronal cell death. As a result, the inflammatory response must be tightly regulated and unique mechanisms contribute to the immune response in the CNS. Early restriction of virus replication is accomplished by the innate immune response upon activation of pattern recognition receptors in resident cells. Infiltrating immune cells enter from the periphery to clear virus. Antibodies and interferon-γ are primary contributors to noncytolytic clearance of virus in the CNS. Lymphocytes are retained in the CNS after the acute phase of infection presumably to block reactivation of virus replication. url: https://api.elsevier.com/content/article/pii/B9780123742797140226 doi: 10.1016/b978-0-12-374279-7.14022-6 id: cord-312075-asbt0mcj author: Schulz, Katharina S. title: Viral Evasion Strategies in Type I IFN Signaling – A Summary of Recent Developments date: 2016-11-11 words: 5763.0 sentences: 388.0 pages: flesch: 46.0 cache: ./cache/cord-312075-asbt0mcj.txt txt: ./txt/cord-312075-asbt0mcj.txt summary: Human T-cell lymphotropic virus type I (HTLV-1) protein Tax disrupts innate immune signaling in multiple ways: it binds to the RIP homotypic interaction motif (RHIM) domains of RIP-1 and disrupts the interaction between RIP-1 and RIG-I or MDA-5 and the activation of the type I IFN promoter. Upon stimulation, TBK1 and IKKε are recruited by adaptor proteins to signaling complexes to be activated by phosphorylation on Ser172 and both have been shown to be subjected to K63-linked polyubiquitination [reviewed in Ref. Interestingly, when a recent study tested how the rabies virus P protein of street strains behaves compared to laboratory-adapted strains with regard to the induction of type I IFN, they found that both street strains and laboratory strains inhibit TBK1-mediated signaling, but only the P protein of street strains also interacts with and inhibits IKKε-inducible IRF3dependent IFNβ expression (88) (Figure 1) . Middle east respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3 abstract: The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which then causes an antiviral state in the cells. However, many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. In this article, we will review examples of viruses that modulate the IFN response and describe the mechanisms they use. url: https://www.ncbi.nlm.nih.gov/pubmed/27891131/ doi: 10.3389/fimmu.2016.00498 id: cord-012418-6ralcn8p author: Schwanke, Hella title: Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression date: 2020-07-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The type I interferon (IFN) response is a principal component of our immune system that allows to counter a viral attack immediately upon viral entry into host cells. Upon engagement of aberrantly localised nucleic acids, germline-encoded pattern recognition receptors convey their find via a signalling cascade to prompt kinase-mediated activation of a specific set of five transcription factors. Within the nucleus, the coordinated interaction of these dimeric transcription factors with coactivators and the basal RNA transcription machinery is required to access the gene encoding the type I IFN IFNβ (IFNB1). Virus-induced release of IFNβ then induces the antiviral state of the system and mediates further mechanisms for defence. Due to its key role during the induction of the initial IFN response, the activity of the transcription factor interferon regulatory factor 3 (IRF3) is tightly regulated by the host and fiercely targeted by viral proteins at all conceivable levels. In this review, we will revisit the steps enabling the trans-activating potential of IRF3 after its activation and the subsequent assembly of the multi-protein complex at the IFNβ enhancer that controls gene expression. Further, we will inspect the regulatory mechanisms of these steps imposed by the host cell and present the manifold strategies viruses have evolved to intervene with IFNβ transcription downstream of IRF3 activation in order to secure establishment of a productive infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411613/ doi: 10.3390/v12070733 id: cord-306424-gf0bglm0 author: Scutigliani, Enzo Maxim title: Interaction of the innate immune system with positive-strand RNA virus replication organelles date: 2017-06-27 words: 8320.0 sentences: 382.0 pages: flesch: 36.0 cache: ./cache/cord-306424-gf0bglm0.txt txt: ./txt/cord-306424-gf0bglm0.txt summary: Thus, these data indicate that MAMs are critical locations for antiviral signaling and have an important role in expression of type I and III IFNs. Moreover, increasing evidence suggests that at least some +RNA viruses in fact occupy or hijack MAM-membranes during infection, as MAMs of HCV-infected cells were found to contain proteins involved in virus assembly and fully assembled virions [111] . At last, based on recent studies that demonstrated how IFN-g inducible GTPases are capable of disrupting PVs, we discussed the possibility of a general function of IFN-inducible GTPases in the targeting of viral ROs. In summary, upon infection, +RNA viruses hamper IFN and ISG induction at multiple levels to decelerate antiviral innate immune signaling. Antiviral innate immune response interferes with the formation of replication-associated membrane structures induced by a +RNA virus abstract: The potential health risks associated with (re-)emerging positive-strand RNA (+RNA) viruses emphasizes the need for understanding host-pathogen interactions for these viruses. The innate immune system forms the first line of defense against pathogenic organisms like these and is responsible for detecting pathogen-associated molecular patterns (PAMPs). Viral RNA is a potent inducer of antiviral innate immune signaling, provoking an antiviral state by directing expression of interferons (IFNs) and pro-inflammatory cytokines. However, +RNA viruses developed various methods to avoid detection and downstream signaling, including isolation of viral RNA replication in membranous viral replication organelles (ROs). These structures therefore play a central role in infection, and consequently, loss of RO integrity might simultaneously result in impaired viral replication and enhanced antiviral signaling. This review summarizes the first indications that the innate immune system indeed has tools to disrupt viral ROs and other non- or aberrant-self membrane structures, and may do this by marking these membranes with proteins such as microtubule-associated protein 1A/1B-light chain 3 (LC3) and ubiquitin, resulting in the recruitment of IFN-inducible GTPases. Further studies should evaluate whether this process forms a general effector mechanism in +RNA virus infection, thereby creating the opportunity for development of novel antiviral therapies. url: https://api.elsevier.com/content/article/pii/S1359610117300667 doi: 10.1016/j.cytogfr.2017.05.007 id: cord-355839-o0m71kvw author: Sedeyn, Koen title: Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses date: 2019-10-17 words: 8187.0 sentences: 414.0 pages: flesch: 45.0 cache: ./cache/cord-355839-o0m71kvw.txt txt: ./txt/cord-355839-o0m71kvw.txt summary: ATF2, activating transcription factor 2; CDS, cytoplasmic DNA sensor; ER, endoplasmic reticulum; IFN, interferon; IKK, inhibitor of nuclear factor kappa-B kinase; IKKε, inhibitor of nuclear factor kappa-B kinase subunit epsilon; IRF3, interferon regulatory factor 3; IRF7, interferon regulatory factor 7; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MAVS, mitochondrial antiviral-signaling protein; MDA5, melanoma differentiation-associated protein 5; MyD88, myeloid differentiation primary response protein MyD88; NF-kB, nuclear factor-kappa B; NOD2, nucleotide-binding oligomerization domain-containing protein 2; PAMP, pathogenassociated molecular pattern; PRR, pattern recognition receptor; RIG, retinoic-acid-inducible gene-I; RLR, RIG-I-like receptor; RSV, respiratory syncytial virus; STING, stimulator of interferon protein; TBK1, tank binding kinase 1; TICAM1, toll/interleukin-1 receptor domain-containing adapter molecule 1; TIRAP, toll/ interleukin-1 receptor domain-containing adapter protein; TLR, toll-like receptor; TRAF3, tumor necrosis factor receptor-associated factor 3; TRAF6, tumor necrosis factor receptor-associated factor 6; TRAM, toll-like receptor adaptor molecule. abstract: Human respiratory syncytial virus (RSV) is the most important cause of acute lower respiratory tract disease in infants worldwide. As a first line of defense against respiratory infections, innate immune responses, including the production of type I and III interferons (IFNs), play an important role. Upon infection with RSV, multiple pattern recognition receptors (PRRs) can recognize RSV-derived pathogen-associated molecular patterns (PAMPs) and mount innate immune responses. Retinoic-acid-inducible gene-I (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) have been identified as important innate receptors to mount type I IFNs during RSV infection. However, type I IFN levels remain surprisingly low during RSV infection despite strong viral replication. The poor induction of type I IFNs can be attributed to the cooperative activity of 2 unique, nonstructural (NS) proteins of RSV, i.e., NS1 and NS2. These viral proteins have been shown to suppress both the production and signaling of type I and III IFNs by counteracting a plethora of key host innate signaling proteins. Moreover, increasing numbers of IFN-stimulated genes (ISGs) are being identified as targets of the NS proteins in recent years, highlighting an underexplored protein family in the identification of NS target proteins. To understand the diverse effector functions of NS1 and NS2, Goswami and colleagues proposed the hypothesis of the NS degradasome (NSD) complex, a multiprotein complex made up of, at least, NS1 and NS2. Furthermore, the crystal structure of NS1 was resolved recently and, remarkably, identified NS1 as a structural paralogue of the RSV matrix protein. Unfortunately, no structural data on NS2 have been published so far. In this review, we briefly describe the PRRs that mount innate immune responses upon RSV infection and provide an overview of the various effector functions of NS1 and NS2. Furthermore, we discuss the ubiquitination effector functions of NS1 and NS2, which are in line with the hypothesis that the NSD shares features with the canonical 26S proteasome. url: https://www.ncbi.nlm.nih.gov/pubmed/31622448/ doi: 10.1371/journal.ppat.1007984 id: cord-310252-0cdqhrcw author: Seliger, Barbara title: Chapter 7 IFN Inducibility of Major Histocompatibility Antigens in Tumors date: 2008-12-03 words: 8538.0 sentences: 422.0 pages: flesch: 43.0 cache: ./cache/cord-310252-0cdqhrcw.txt txt: ./txt/cord-310252-0cdqhrcw.txt summary: Ag, antigen; APC, antigen presenting cells; APM, antigen-processing machinery; BH, bleomycin hydrolase; bp, base pairs; CIITA, class II transactivator protein; CLIP, class II invariant chain peptide; CTL, cytotoxic T lymphocyte; DC, dendritic cell; ER, endoplasmic reticulum; GAS, gammainterferon-activated site; IFN, interferon; IFN-R1, interferon-receptor-1; IL, interleukin; IRF, interferon regulatory factor; ISG, interferon-stimulated genes; ISGF3, IFN-stimulated gene factor 3; ISRE, interferon-stimulated response element; JAK, janus kinase; LPS, lipopolysaccharide; MAPK, mitogenactivated protein kinase; MCA, methylcholanthrene; MHC, major histocompatibility complex; NF, nuclear factor; NK, natural killer; PKC, protein kinase C; RCC, renal cell carcinoma; SCLC, small-cell lung carcinoma; SOCS, suppressor of cytokine signaling; STAT, signal transducer and activator of transcription; TA, tumor antigen; TAP, transporter associated with antigen processing; TCR, T cell receptor; TFBS, transcription factor-binding sites; TNF, tumor necrosis factor; tpn, tapasin; TPPII, tripeptidyl peptidase II; TSA, trichostatin A; TYK, tyrosine kinase; UIRR, upstream interferon response region; USF1, upstream stimulatory factor 1; wt, wild type. abstract: Interferons represent a protein family with pleiotropic functions including immunomodulatory, cytostatic, and cytotoxic activities. Based on these effects, interferons are involved in innate as well as adaptive immunity, thereby shaping the tumor host immune responses. These cytokines, alone or in combination, have been successfully implemented for the treatment of some malignancies. However, it has been recently demonstrated that tumor cells could be resistant to interferon treatment, which may be associated with an escape of tumor cells from immune surveillance. Therefore, the aim of this chapter is to summarize the frequency of impaired interferon signal transduction, their underlying molecular mechanisms, and their clinical relevance. url: https://www.ncbi.nlm.nih.gov/pubmed/19055946/ doi: 10.1016/s0065-230x(08)00407-7 id: cord-307333-n6jc0jy3 author: Selvaggi, Carla title: Interferon lambda 1–3 expression in infants hospitalized for RSV or HRV associated bronchiolitis date: 2014-01-02 words: 6120.0 sentences: 304.0 pages: flesch: 49.0 cache: ./cache/cord-307333-n6jc0jy3.txt txt: ./txt/cord-307333-n6jc0jy3.txt summary: OBJECTIVES: The airway expression of type III interferons (IFNs) was evaluated in infants hospitalized for respiratory syncytial virus (RSV) or rhinovirus (HRV) bronchiolitis. KEYWORDS IFN lambda; IL-28; IL-29; RSV; HRV; MxA; ISG56; Viral load; Bronchiolitis Summary Objectives: The airway expression of type III interferons (IFNs) was evaluated in infants hospitalized for respiratory syncytial virus (RSV) or rhinovirus (HRV) bronchiolitis. Therefore, we evaluated whether there was a difference in the gene expression of IFN lambda 1e3 subtypes between infants with a clinical diagnosis of RSV associated acute bronchiolitis and those with HRV infection. Results demonstrated that in cells collected from nasopharyngeal washings of RSV positive infants there are higher mRNA levels of type III IFNs compared to those observed in infants with Figure 1 Gene expression of IFN lambda 1e3 during RSV or HRV bronchiolitis. abstract: OBJECTIVES: The airway expression of type III interferons (IFNs) was evaluated in infants hospitalized for respiratory syncytial virus (RSV) or rhinovirus (HRV) bronchiolitis. As an additional objective we sought to determine whether a different expression of IFN lambda 1–3 was associated with different harboring viruses, the clinical course of bronchiolitis or with the levels of well established IFN stimulated genes (ISGs), such as mixovirus resistance A (MxA) and ISG56. METHODS: The analysis was undertaken in 118 infants with RSV or HRV bronchiolitis. Nasopharyngeal washes were collected for virological studies and molecular analysis of type III IFN responses. RESULTS: RSV elicited higher levels of IFN lambda subtypes when compared with HRV. A similar expression of type III IFN was found in RSVA or RSVB infected infants and in those infected with HRVA or HRVC viruses. Results also indicate that IFN lambda 1 and IFN lambda 2–3 levels were correlated with each other and with MxA and ISG56-mRNAs. In addition, a positive correlation exists between the IFN lambda1 levels and the clinical score index during RSV infection. In particular, higher IFN lambda 1 levels are associated to an increase of respiratory rate. CONCLUSIONS: These findings show that differences in the IFN lambda 1–3 levels in infants with RSV or HRV infections are present and that the expression of IFN lambda 1 correlates with the severity of RSV bronchiolitis. url: https://api.elsevier.com/content/article/pii/S016344531300399X doi: 10.1016/j.jinf.2013.12.010 id: cord-282246-wyanwvxa author: Sen, Adrish title: Chapter 40 The Role of Innate Immunity in Regulating Rotavirus Replication, Pathogenesis, and Host Range Restriction and the Implications for Live Rotaviral Vaccine Development date: 2020-12-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Rotaviruses (RVs) are important causative agents of viral gastroenteritis in the young of most mammalian species studied, including humans, in which they are the most important cause of severe gastroenteritis worldwide despite the availability of several safe and effective vaccines. Replication of RVs is restricted in a host species-specific manner, and this barrier is determined predominantly by the host interferon (IFN) signaling and the ability of different RV strains to successfully negate IFN activation and amplification pathways. In addition, viral attachment to the target intestinal epithelial cells also regulates host range restriction. Several studies have focused on the role of the innate immune response in regulating RV replication and pathogenesis. The knowledge accrued from these efforts is likely to result in rational attenuation of RV vaccines to closely match circulating (and host species-matched) virus strains. In this chapter, we review prevalent models of RV interactions with innate immune factors, viral strategies employed to regulate their function, and the implications of these findings for improved RV vaccine development. url: https://api.elsevier.com/content/article/pii/B9780128119242000419 doi: 10.1016/b978-0-12-811924-2.00041-9 id: cord-270103-g9a72xf6 author: Shin, Hye Jin title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity date: 2018-04-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Nucleoside analogs have been frequently identified as antiviral agents. In recent years, gemcitabine, a cytidine analog in clinical use for the treatment of many solid tumors, was also shown to have antiviral activity against a broad range of viruses. Nucleoside analogs generally interfere with cellular nucleos(t)ide synthesis pathways, resulting in the depletion or imbalance of (d)NTP pools. Intriguingly, a few recent reports have shown that some nucleoside analogs, including gemcitabine, activated innate immunity, inducing the expression of interferon-stimulated genes, through nucleos(t)ide synthesis inhibition. The precise crosstalk between these two independent processes remains to be determined. Nonetheless, we summarize the current knowledge of nucleos(t)ide synthesis inhibition-related innate immunity and propose it as a newly emerging antiviral mechanism of nucleoside analogs. url: https://doi.org/10.3390/v10040211 doi: 10.3390/v10040211 id: cord-001676-68y733y3 author: Shoemaker, Jason E. title: An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation date: 2015-06-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza viruses present major challenges to public health, evident by the 2009 influenza pandemic. Highly pathogenic influenza virus infections generally coincide with early, high levels of inflammatory cytokines that some studies have suggested may be regulated in a strain-dependent manner. However, a comprehensive characterization of the complex dynamics of the inflammatory response induced by virulent influenza strains is lacking. Here, we applied gene co-expression and nonlinear regression analysis to time-course, microarray data developed from influenza-infected mouse lung to create mathematical models of the host inflammatory response. We found that the dynamics of inflammation-associated gene expression are regulated by an ultrasensitive-like mechanism in which low levels of virus induce minimal gene expression but expression is strongly induced once a threshold virus titer is exceeded. Cytokine assays confirmed that the production of several key inflammatory cytokines, such as interleukin 6 and monocyte chemotactic protein 1, exhibit ultrasensitive behavior. A systematic exploration of the pathways regulating the inflammatory-associated gene response suggests that the molecular origins of this ultrasensitive response mechanism lie within the branch of the Toll-like receptor pathway that regulates STAT1 phosphorylation. This study provides the first evidence of an ultrasensitive mechanism regulating influenza virus-induced inflammation in whole lungs and provides insight into how different virus strains can induce distinct temporal inflammation response profiles. The approach developed here should facilitate the construction of gene regulatory models of other infectious diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457877/ doi: 10.1371/journal.ppat.1004856 id: cord-023433-d1b7qvhs author: Siassi, M. title: Expression of Human Collectins in Colorectal Carcinoma date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Introduction: The human collectins, mannan‐binding lectin (MBL), surfactant protein‐A (SP‐A) and surfactant‐protein‐D (SP‐D) play a central role in the innate immune system. Immunological responses to malignant transformation of epithelial cells gained increasing interest recently. A former study could demonstrate binding of MBL to certain colorectal carcinoma (CRC) cell lines in vitro. We therefore examined the expression of human collectins in normal colon mucosa and in colorectal carcinomas. Materials and methods: Colon samples from 20 CRC patients and 10 normal mucosa samples were collected immediately after surgery. The tissue was microdissected and RNA isolated (Qiagen, Rneasy‐Kit). Gene expression profiles were analysed using Gene‐chips (Affymetrix, HG‐U133). We analysed the data for the expression of MBL, its associated serine proteases mannan‐binding lectin‐associated serine protease 1/2 (MASP 1/2), SP‐A and SP‐D. The signal intensity of the genes of interest was compared using the Mann–Whitney U‐test. Results: The expression of human collectins in normal human colon mucosa was generally low. Only the expression of SP‐A and MASP‐2 reached the noise threshold of 250 signals. These genes were significantly downregulated in CRC specimens. The expression of the other proteins showed no difference in normal mucosa and CRC. Conclusion: As demonstrated before, the expression of human collectins in normal colon was low in this study. Only SP‐A showed a significant expression in normal mucosa which was downregulated in CRC. As the absolute signal level was below the noise threshold, these results have to be interpreted with caution and require confirmation by direct measurenment of the proteins. Our results suggest that there is no major role for the human collectins in colorectal cancer. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169588/ doi: 10.1111/j.0300-9475.2004.01423bo.x id: cord-023431-zjyrhlxn author: Sigmundsdóttir, H. title: Differential Effects of Interleukin‐12 and Interleukin‐10 on Superantigen‐Induced Expression of Cutaneous Lymphocyte‐Associated Antigen and αEβ7 Integrin (CD103) by CD8(+) T cells date: 2008-06-28 words: 16867.0 sentences: 869.0 pages: flesch: 46.0 cache: ./cache/cord-023431-zjyrhlxn.txt txt: ./txt/cord-023431-zjyrhlxn.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: The interaction with adhesion molecules expressed by vascular endothelium is the first step in lymphocyte infiltration into tissues. At both cutaneous and mucosal sites interleukin‐10 (IL‐10), IL‐12 and transforming growth factor (TGF)‐β are important regulators of chronic inflammatory disease, where cutaneous lymphocyte‐associated antigen (CLA) and αE integrin (CD103) may be expressed. Unlike CLA, CD103 is not believed to play a role in tissue‐specific homing but may help to retain T cells within epithelial layers. We have previously shown that IL‐12 alone can together with an unknown cofactor increase the expression of CLA. Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8(+) but not CD4(+) T cells. While IL‐12 increased superantigen‐stimulated expression of CLA, this cytokine strongly inhibited the CD103 expression, and a combination of IL‐12 and TGF‐β completely abrogated the induced CD103 expression. Conversely, IL‐10 suppressed CLA but increased CD103 expression. These findings indicate that, in addition to suppressing the development of Th1‐mediated inflammatory responses, IL‐10 may also inhibit the migration of CD8(+) T cells into the skin while IL‐12 promotes such migration. Thus, the expression of CLA and CD103 may be antagonistically regulated by IL‐10 and IL‐12, and the balance between these cytokines could influence the T‐cell migration of inflammatory cells into epithelial tissues. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169583/ doi: 10.1111/j.0300-9475.2004.01423ab.x id: cord-285148-bch7814v author: Singanayagam, Aran title: Viruses exacerbating chronic pulmonary disease: the role of immune modulation date: 2012-03-15 words: 7923.0 sentences: 393.0 pages: flesch: 35.0 cache: ./cache/cord-285148-bch7814v.txt txt: ./txt/cord-285148-bch7814v.txt summary: However in vitro RV infection of epithelial cells from COPD patients resulted in higher virus load and increased inflammatory mediators, but no differences in interferon production compared to cells from control subjects [87] . List of abbreviations ATF: activating transcription factor; BAL: bronchoalveolar lavage; CF: cystic fibrosis; CFTR: cystic fibrosis transmembrane regulator; COPD: chronic obstructive pulmonary disease; ENA-78: epithelial-derived neutrophilactivating peptide 78; ICAM-1: intercellular adhesion molecule; IFN-α: interferon-alpha; IFN-β: interferon-beta; IFN-λ: interferon-lambda; IFN-γ: interferon-gamma; IL: interleukin; IP-10: IFN-γ-induced protein-10; IRF: interferon regulatory factor; ISG: interferon stimulated genes; MDA-5: melanoma differentiation-associated protein-5; NF-κB: nuclear factor-kappa B; NO: nitric oxide; NOS2: nitric oxide synthase 2; PCR: polymerase chain reaction; PEF: peak expiratory flow; PIV: parainfluenza virus; RANTES: regulated on activation: normal T-cell expressed and secreted; RIG-I: retinoic acid inducible gene I; RSV: respiratory syncytial virus; RV: rhinovirus; SLPI: secretory leukoprotease inhibitor; SOCS: suppressor of cytokine signaling family; Th1/2: T helper 1/2; TLR: toll-like receptors; TNF-α: tumor necrosis factor-alpha -1. abstract: Chronic pulmonary diseases are a major cause of morbidity and mortality and their impact is expected to increase in the future. Respiratory viruses are the most common cause of acute respiratory infections and it is increasingly recognized that respiratory viruses are a major cause of acute exacerbations of chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. There is now increasing evidence that the host response to virus infection is dysregulated in these diseases and a better understanding of the mechanisms of abnormal immune responses has the potential to lead to the development of new therapies for virus-induced exacerbations. The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in chronic pulmonary diseases and discuss avenues for future research and therapeutic implications. url: https://doi.org/10.1186/1741-7015-10-27 doi: 10.1186/1741-7015-10-27 id: cord-338320-jc00ulx5 author: Siu, Kam-Leung title: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain date: 2014-02-10 words: 3684.0 sentences: 238.0 pages: flesch: 53.0 cache: ./cache/cord-338320-jc00ulx5.txt txt: ./txt/cord-338320-jc00ulx5.txt summary: title: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. 12 , 13 We have previously reported that SARS coronavirus M protein suppresses type I IFN production potently by preventing the formation of functional TRAF3-TANK-TBK1/IKKe complex. IFN antagonism of SARS coronavirus M protein was mediated by N-terminal TM1 (amino acids 1-38), which targets M protein to the Golgi complex and associates with TRAF3 to prevent it from interacting with TANK, TBK1 and IKKe. Our findings provide additional molecular details for suppression of type I IFN production by SARS coronavirus M protein. Notably, human coronavirus HKU1 M protein also targets the Golgi complex, interacts with TRAF3, but does not suppress IFN production. abstract: Coronaviruses have developed various measures to evade innate immunity. We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. M protein from human coronavirus HKU1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response. url: https://doi.org/10.1038/cmi.2013.61 doi: 10.1038/cmi.2013.61 id: cord-341278-klv9jdm8 author: Smith, Abigail L. title: The role of gamma interferon in infection of susceptible mice with murine coronavirus, MHV-JHM date: 1991 words: 3861.0 sentences: 182.0 pages: flesch: 45.0 cache: ./cache/cord-341278-klv9jdm8.txt txt: ./txt/cord-341278-klv9jdm8.txt summary: Infection of BALB/c mice with mouse hepatitis virus, strain JHM (MHV-JHM), at any of several intervals relative to ovalbumin (OVA) administration resulted in elevated OVA-specific IgG 2 a titers. Serum IFN-γ was not detected, but treatment of MHV-JHM-infected mice with monoclonal anti-IFN-γ antibody resulted in high mortality with decreased survival times, enhanced virus titers in liver and spleen, and more severe virus-associated pathology, compared to mock-treated, infected mice. Sera from mice infected with MHV-JHM one day prior to OVA administration contained substantially elevated levels of antigen-specific IgG2 a on day 7 (Table 1 ) with geometric mean titers that were 17 times control (OVA only) values at that interval. The elevated IgG 2 a OVA-specific response of most groups of MHV-infected mice and the preferential production of this isotype by mice infected one day prior to antigen administration suggested that these mice were producing IFNy. However, using the WEHI 279 B cell lymphoma bioassay [24] , attempts to detect the cytokine in sera of infected mice failed, as had earlier attempts to 27] . abstract: Infection of BALB/c mice with mouse hepatitis virus, strain JHM (MHV-JHM), at any of several intervals relative to ovalbumin (OVA) administration resulted in elevated OVA-specific IgG 2 a titers. Since gamma interferon (IFN) has been implicated as an up-regulator of IgG 2 a production, attempts were made to determine whether levels of this cytokine were modified in sera of infected mice. Serum IFN-γ was not detected, but treatment of MHV-JHM-infected mice with monoclonal anti-IFN-γ antibody resulted in high mortality with decreased survival times, enhanced virus titers in liver and spleen, and more severe virus-associated pathology, compared to mock-treated, infected mice. Immunotherapy with recombinant IFN-γ ameliorated disease as reflected by mortality rates and virus titers in target organs. url: https://www.ncbi.nlm.nih.gov/pubmed/1662041/ doi: 10.1007/bf01316746 id: cord-275690-83nrzfon author: Stanifer, Megan L. title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date: 2020-04-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: SARS-CoV-2 is an unprecedented worldwide health problem that requires concerted and global approaches to better understand the virus in order to develop novel therapeutic approaches to stop the COVID-19 pandemic and to better prepare against potential future emergence of novel pandemic viruses. Although SARS-CoV-2 primarily targets cells of the lung epithelium causing respiratory infection and pathologies, there is growing evidence that the intestinal epithelium is also infected. However, the importance of the enteric phase of SARS-CoV-2 for virus-induced pathologies, spreading and prognosis remains unknown. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of SARS-CoV-2 lifecycle in human intestinal epithelial cells. Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, we identified intestinal epithelial cells as the best culture model to propagate SARS-CoV-2. We found that viral infection elicited an extremely robust intrinsic immune response where, interestingly, type III interferon mediated response was significantly more efficient at controlling SARS-CoV-2 replication and spread compared to type I interferon. Taken together, our data demonstrate that human intestinal epithelial cells are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing in increasing patient viremia and by fueling an exacerbated cytokine response. url: https://doi.org/10.1101/2020.04.24.059667 doi: 10.1101/2020.04.24.059667 id: cord-314505-7qh8dsew author: Stegelmeier, Ashley A. title: Myeloid Cells during Viral Infections and Inflammation date: 2019-02-19 words: 12519.0 sentences: 640.0 pages: flesch: 35.0 cache: ./cache/cord-314505-7qh8dsew.txt txt: ./txt/cord-314505-7qh8dsew.txt summary: The induction of the IFN response following viral infections fundamentally changes the bone marrow microenvironment ( Figure 1B) , leading to the enhanced differentiation of myeloid cells [24] and emigration of neutrophils and monocytes to the site of infection, which is facilitated by chemokine gradients interacting with their cognate receptors ( Figure 1A ) [25] . TLR stimulation after phagocytosis activates the NF-κB signaling cascade, resulting in the release of inflammatory cytokines such as TNF-α, IL-1, and IL-6 from monocytes [4] to control virus infections by direct antiviral mechanisms and the recruitment of other leukocytes. Taken together, these findings suggest that type I IFN signaling drives a balance of pro-and anti-inflammatory effects on the functions of monocytes and neutrophils in response to viral infections; providing protective immunity while simultaneously limiting immunopathology. Importantly, viruses and virus-mediated tissue damage stimulate both neutrophils and monocytes, triggering a cascade of cytokine/chemokine-mediated innate immune responses. abstract: Myeloid cells represent a diverse range of innate leukocytes that are crucial for mounting successful immune responses against viruses. These cells are responsible for detecting pathogen-associated molecular patterns, thereby initiating a signaling cascade that results in the production of cytokines such as interferons to mitigate infections. The aim of this review is to outline recent advances in our knowledge of the roles that neutrophils and inflammatory monocytes play in initiating and coordinating host responses against viral infections. A focus is placed on myeloid cell development, trafficking and antiviral mechanisms. Although known for promoting inflammation, there is a growing body of literature which demonstrates that myeloid cells can also play critical regulatory or immunosuppressive roles, especially following the elimination of viruses. Additionally, the ability of myeloid cells to control other innate and adaptive leukocytes during viral infections situates these cells as key, yet under-appreciated mediators of pathogenic inflammation that can sometimes trigger cytokine storms. The information presented here should assist researchers in integrating myeloid cell biology into the design of novel and more effective virus-targeted therapies. url: https://www.ncbi.nlm.nih.gov/pubmed/30791481/ doi: 10.3390/v11020168 id: cord-023419-lnmc6vv5 author: Steinhauer, C. title: High‐Throughput Proteomics on Antibody‐based Microarrays: the Importance of Probe and Surface Design date: 2008-06-28 words: 16884.0 sentences: 871.0 pages: flesch: 46.0 cache: ./cache/cord-023419-lnmc6vv5.txt txt: ./txt/cord-023419-lnmc6vv5.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: In analogy to DNA microarrays, protein microarrays offer a new distinct possibility to perform sensitive high‐throughput global proteome analysis. However, the development of the protein microarray technology will place high demands upon the design of both probes and solid supports. The analysis of thousands of heterogeneous proteins on a single microarray requires the use of uniform probes, such as antibodies, directly designed for protein microarray applications. We have recently generated a human recombinant single‐chain Fv antibody library, genetically constructed around one framework, the nCoDeR‐library, containing 2 × 1010 clones. Single framework antibody fragments (sinFabs) selected from this library were successfully applied as probes for microarrays providing sensitive detection in the 600 attomol (mass spectrometry) and the 300 zeptomole range (fluorescence). However, the choice of framework is critical. We have shown that the selected nCoDeR framework displayed excellent functional on‐chip stability and arrayed dehydrated probes retained their activity for several months. Furthermore, we have addressed the issues of biocompatibility of the solid support and immobilization strategies for our microarray setup. An in‐house‐designed substrate, macroporous silicon coated with nitrocellulose (MAP3‐NC7), displayed properties equal to, or better than, those of five commercially available supports used as reference surfaces. We have also evaluated different coupling strategies, such as adsorption, covalent coupling, diffusion and affinity coupling. Using a novel affinity tag, the double‐(his)6‐tag, we increased the binding efficiency of sinFab‐molecules to Ni2(+)‐coated solid supports, thereby allowing nonpurified probes to be directly applied. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169563/ doi: 10.1111/j.0300-9475.2004.01423ax.x id: cord-256325-q70rky3r author: Stewart, Cameron R. title: A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease date: 2017-07-04 words: 8310.0 sentences: 409.0 pages: flesch: 43.0 cache: ./cache/cord-256325-q70rky3r.txt txt: ./txt/cord-256325-q70rky3r.txt summary: title: A Functional Genomics Approach to Henipavirus Research: The Role of Nuclear Proteins, MicroRNAs and Immune Regulators in Infection and Disease Here we largely focus on findings from two recent RNAi screens to identify protein-coding genes and host-encoded microRNAs impacting the henipavirus infection cycle in human cells. X-ray data have suggested that the methylation of rRNA requires the formation of this complex with involvement of four fibrillarin molecules interacting with different regions of the target rRNAs. The yeast equivalent of fibrillarin, NOP1, has been more extensively studied than the human counterpart but fibrillarin is a well-conserved protein in most organisms, reinforcing the notion that all post-transcriptional processes involving fibrillarin such as chemical modification (methylation) of rRNA, pre-rRNA cleavage and ribosome assembly are essential for proper cellular functioning (Rodriguez-Corona et al. Deffrasnes and colleagues showed that siRNA-mediated knockdown of fibrillarin expression dramatically reduced HeV protein production and viral genome replication but did not impact viral fusion, and that fibrillarin catalytic activity was essential to henipavirus infection. abstract: Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are zoonotic RNA viruses that cause lethal disease in humans and are designated as Biosafety Level 4 (BSL4) agents. Moreover, henipaviruses belong to the same group of viruses that cause disease more commonly in humans such as measles, mumps and respiratory syncytial virus. Due to the relatively recent emergence of the henipaviruses and the practical constraints of performing functional genomics studies at high levels of containment, our understanding of the henipavirus infection cycle is incomplete. In this chapter we describe recent loss-of-function (i.e. RNAi) functional genomics screens that shed light on the henipavirus–host interface at a genome-wide level. Further to this, we cross-reference RNAi results with studies probing host proteins targeted by henipavirus proteins, such as nuclear proteins and immune modulators. These functional genomics studies join a growing body of evidence demonstrating that nuclear and nucleolar host proteins play a crucial role in henipavirus infection. Furthermore these studies will underpin future efforts to define the role of nucleolar host–virus interactions in infection and disease. url: https://doi.org/10.1007/82_2017_28 doi: 10.1007/82_2017_28 id: cord-318339-j35w1vsw author: Stockman, Lauren J title: SARS: Systematic Review of Treatment Effects date: 2006-09-12 words: 4388.0 sentences: 233.0 pages: flesch: 50.0 cache: ./cache/cord-318339-j35w1vsw.txt txt: ./txt/cord-318339-j35w1vsw.txt summary: METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. This paper reports on this systematic review designed to summarise available evidence on the effects of ribavirin, lopinavir and ritonavir (LPV/r), corticosteroids, type I IFN, intravenous immunoglobulin (IVIG), or convalescent plasma in relation to (1) SARS-CoV replication inhibition in vitro; (2) mortality or morbidity in SARS patients; and (3) effects on ARDS in adult patients. abstract: BACKGROUND: The SARS outbreak of 2002–2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment. url: https://www.ncbi.nlm.nih.gov/pubmed/16968120/ doi: 10.1371/journal.pmed.0030343 id: cord-279725-d82sj80v author: Ströher, Ute title: Severe Acute Respiratory Syndrome-Related Coronavirus Is Inhibited by Interferon-α date: 2004-04-01 words: 2235.0 sentences: 126.0 pages: flesch: 52.0 cache: ./cache/cord-279725-d82sj80v.txt txt: ./txt/cord-279725-d82sj80v.txt summary: We evaluated the susceptibility of the SARS-related coronavirus (SARS CoV) to ribavirin and interferon (IFN)-α in vitro by use of cytopathic effect, plaque assay, and immunoblot analysis. To support the search for effective antiviral treatments, we evaluated the susceptibility of SARS CoV isolates (detailed studies were performed with the Tor2 isolate [Toronto, Canada]) to ribavirin and interferon (IFN)-a-2b in vitro. Our data indicate that ribavirin does not inhibit the virus at concentrations attainable in human serum but that IFN-a-2b may be useful and deserves further evaluation as a therapeutic agent. To quantify the effect of IFN-a-2b on the replication of the SARS CoV, Vero E6 cells were infected at an MOI of 0.001 and were incubated in the presence IFN-a-2b (0-5000 IU/mL), as described above. Whether combined therapy with IFN-a-2b and ribavirin would inhibit the replication of the SARS CoV in vitro has not yet been evaluated; the combination is more effective than either agent used alone for the treatment of HCV infection in humans. abstract: Current treatment schemes for severe acute respiratory syndrome (SARS) include broad-spectrum antibiotics, glucocorticoids, and ribavirin. We evaluated the susceptibility of the SARS-related coronavirus (SARS CoV) to ribavirin and interferon (IFN)-α in vitro by use of cytopathic effect, plaque assay, and immunoblot analysis. Ribavirin did not inhibit viral growth at concentrations attainable in human serum. In contrast, IFN-α showed an in vitro inhibitory effect starting at concentrations of 1000 IU/mL. In conclusion, ribavirin alone is unlikely to be beneficial in the prophylaxis or treatment of SARS CoV infections. Clinical trials with IFN-α might be justified to determine a beneficial effect on the outcome of SARS. url: https://www.ncbi.nlm.nih.gov/pubmed/15031783/ doi: 10.1086/382597 id: cord-023374-87ob1exq author: Sukhija, S. title: Levels, Complement Activity and Polymorphisms of Mannan‐Binding Lectin in Patients of Bronchial Asthma with Allergic Rhinitis date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Activation of complement pathways, leading to production of C3a and C5a anaphylatoxins, has been postulated in the pathogenesis of asthma and allergic airway inflammation. The present study was undertaken to investigate the role of mannan‐binding lectin (MBL), an initiator of the lectin pathway of complement, in asthma and allergic rhinitis. MBL levels and MBL‐induced complement activity were determined in 19 patients of bronchial asthma with allergic rhinitis and 20 unrelated, age‐matched controls of Indian origin. MBL levels and activity were correlated with percent eosinophilia and percent predicted FEV1 values of the patients. Association of single nucleotide polymorphisms (SNPs) in exon 1 and intron 1 of the MBL with the disease, clinical markers, MBL levels and MBL‐induced complement activity was analysed using standard statistical tools. Significantly higher MBL levels and activity were observed in patients of bronchial asthma with allergic rhinitis as compared to the controls. We identified five SNPs, of which two, A816G in exon 1 and G1011A in intron 1 of the MBL, were novel. SNP G1011A was significantly associated with the disease (P = 0.0024, OR = 5.8696, 95% CI: 1.7316 < OR < 19.8963). Individuals with ‘A’ allele at position 1011 showed increased MBL levels, activity and disease severity. Our results suggest that ‘A’ allele at position 1011 leading to high MBL levels and complement activity may be contributing to the severity of bronchial asthma and allergic airway inflammation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169489/ doi: 10.1111/j.0300-9475.2004.01423ai.x id: cord-297512-l9re9h4j author: Sultana, Shehnaz title: Interferon gamma (IFNγ) +874A/T gene polymorphism in South Indian ischemic stroke patients date: 2011-07-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Ischemic stroke is a complex vascular and metabolic process resulting in neuronal death and progression with time. Cytokines play a role in immune response and also maintains the normal homeostatic environment of the central nervous system. IFN-γ is one of the key effector cytokines produced by NK and T cells that enhances microbicidal activity of macrophages and neutrophils. PURPOSE: As the association of IFNγ +874A/T gene polymorphism with stroke has not been investigated in Indian population, we wanted to evaluate the association of this polymorphism with ischemic stroke in a South Indian population. METHODS: We genotyped 171 ischemic stroke patients and 153 age-matched control subjects. RESULTS: Statistical analysis showed a significant association of TT homozygote with ischemic stroke (OR=1.9, 95% CI=1.05-3.43, p=0.03), while AA (OR= 0.84, 95% CI=0.54–1.31, p=0.46) and AT(OR=0.80, 95% CI=0.51-1.26, p=0.34) genotypes were not significantly associated. A and T allele frequencies in stroke were 58.78% and 41.22% as against 65.36% and 34.64% in control group, respectively, thus, suggesting no statistically significant differences in the A (OR=0.75, 95% CI=0.54–1.03, p=0.08) and T (OR=1.32, 95% CI=0.96– 1.82, p=0.08) allele frequencies between the two groups. CONCLUSION: We conclude that the IFN-γ +874 TT genotype is associated with the increased risk of ischemic stroke. url: https://www.ncbi.nlm.nih.gov/pubmed/25205933/ doi: 10.5214/ans.0972.7531.1118305 id: cord-256788-h4iv8crq author: Sumino, Kaharu title: Antiviral IFN-γ responses of monocytes at birth predict respiratory tract illness in the first year of life date: 2012-03-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Viral respiratory tract infections are the leading cause of acute illness during infancy and are closely linked to chronic inflammatory airway diseases later in life. However, the determinants of susceptibility to acute respiratory tract infections still need to be defined. OBJECTIVE: We investigated whether the individual variation in antiviral response at birth determines the risk for acute respiratory tract illness in the first year of life. METHODS: We studied 82 children who were enrolled in a birth cohort study of inner-city children with at least 1 parent with allergy or asthma. We cultured cord blood monocytes and assessed IFNG and CCL5 mRNA production at 24 hours after inoculation with respiratory syncytial virus. We also monitored the frequency of acute respiratory tract illness at 3-month intervals and analyzed nasal lavage samples for respiratory tract viruses at the time of illness during the first year. RESULTS: Respiratory tract infection was reported for 88% of subjects, and respiratory tract viruses were recovered in 74% of symptomatic children. We observed a wide range of antiviral responses in cord blood monocytes across the population. Furthermore, a decrease in production of IFNG (but not CCL5) mRNA in response to respiratory syncytial virus infection of monocytes was associated with a significant increase in the frequency of upper respiratory tract infections (r = −0.42, P < .001) and the prevalence of ear and sinus infections, pneumonias, and respiratory-related hospitalizations. CONCLUSION: Individual variations in the innate immune response to respiratory tract viruses are detectable even at birth, and these differences predict the susceptibility to acute respiratory tract illness during the first year of life. url: https://www.ncbi.nlm.nih.gov/pubmed/22460071/ doi: 10.1016/j.jaci.2012.02.033 id: cord-259669-fod4xkd7 author: Summerfield, Artur title: The porcine dendritic cell family date: 2008-06-06 words: 9379.0 sentences: 489.0 pages: flesch: 46.0 cache: ./cache/cord-259669-fod4xkd7.txt txt: ./txt/cord-259669-fod4xkd7.txt summary: Being strategically located at sites of pathogen entry, such as mucosal surfaces and Considering the pivotal roles played by dendritic cells (DCs) in both innate and adaptive immune responses, advances in the field of porcine immunology DC biology have recently progressed rapidly. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. Altogether, the co-expression of CD172a and CD1 along with relatively high levels of both CD80/86 and MHC class II represent phenotypic characteristics of porcine MoDC but no marker clearly differentiating them from monocyte-derived macrophages has been identified. abstract: Considering the pivotal roles played by dendritic cells (DCs) in both innate and adaptive immune responses, advances in the field of porcine immunology DC biology have recently progressed rapidly. As with the more extensively studied murine and human DCs, porcine DC can be generated from bone marrow haematopoietic cells or monocytes, and have been analysed in various immunological and non-immunological tissues. Both conventional DC (cDC) and plasmacytoid DC (pDC) have been characterized. The function of porcine monocyte-derived DC has not only been characterized in terms of antigen presentation and lymphocyte activation, but also their response to various ligands of pattern recognition receptors. These have been characterized in terms of the induction of DC maturation and pro-inflammatory, Th1-like or Th2-like cytokines secretion. Porcine pDC most effectively sense virus infections and are characterized by their capacity to produce large quantities of IFN-α and the pro-inflammatory cytokines TNF-α, IL-6 and IL-12. As such, the DC family as a whole is a powerful ally in the host battle against pathogen attack. Nevertheless, DC in particular tissue environments or under particular stimuli can down-regulate immune response development. This is not only important for preventing over-activation of the immune system and also for ensuring tolerance against self or “friendly” substances including food components, but may also be used as a mechanism of pathogens to evade immune responses. url: https://www.sciencedirect.com/science/article/pii/S0145305X08001031 doi: 10.1016/j.dci.2008.05.005 id: cord-318364-5bmdzgla author: Sun, Xinjuan title: Cytokine storm intervention in the early stages of COVID-19 pneumonia date: 2020-04-25 words: 3102.0 sentences: 158.0 pages: flesch: 40.0 cache: ./cache/cord-318364-5bmdzgla.txt txt: ./txt/cord-318364-5bmdzgla.txt summary: In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response. In support of the above observations, a retrospective study of 41 patients with COVID-19 2 showed that most SARS-CoV-2 infected patients present clinically with mild symptoms, while a minority of patients progressively declined from the infection and eventually died of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MOD). Severe pneumonia caused by pathogenic human coronaviruses (HCoV) are often associated with induced hypercytokinemia, also termed cytokine storm, in immunocompetent individuals; uncontrolled overproduction of inflammatory cytokines contributes to acute lung injury and acute respiratory distress syndrome (ARDS). abstract: Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30(th), 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response. url: https://api.elsevier.com/content/article/pii/S1359610120300484 doi: 10.1016/j.cytogfr.2020.04.002 id: cord-001834-6xf4o3oy author: Sung, Pil Soo title: Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection date: 2015-10-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130–170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant. The development of cell culture-derived HCV (HCVcc) systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses. Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection. Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632721/ doi: 10.3390/ijms161023683 id: cord-000164-094d0rn6 author: Suthar, Mehul S. title: IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity date: 2010-02-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV. IPS-1(−/−) mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1(−/−) mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection. Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816698/ doi: 10.1371/journal.ppat.1000757 id: cord-023421-1d1gf7az author: Sønder, S. U. S. title: Monitoring Patients Treated with Type 1 Interferons: Antiviral versus MxA Induction Assays date: 2008-06-28 words: 16866.0 sentences: 873.0 pages: flesch: 46.0 cache: ./cache/cord-023421-1d1gf7az.txt txt: ./txt/cord-023421-1d1gf7az.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: Interferon‐α/β (IFN‐α/β) is increasingly used as antiviral and immunomodulatory therapies. Unfortunately, bioavailability varies with IFN species and mode of administration, and all IFN species are potentially immunogenic. Assays for antiviral activity (IFN) and antiviral neutralization (antibodies, NAb) have been used for some time to monitor patients on IFN biologicals. These assays require laborious titrations making them unsuitable for large‐scale clinical use. Our laboratories have therefore modified the antiviral assays for IFN bioactivity and Nab, so that they are suitable for large‐scale screening in specialized laboratories. The read‐out is survival of a subcloned A549 cell line in the presence of an otherwise lethal amount of virus. Thus, survival increases in the presence of type 1 IFN and decreases in the presence of NAb against the IFN added to the cells. MxA is induced by type 1 IFN and can be used for measuring the Nab activity. In another assay, the MxA level in the A549 cell line is measured. In an attempt to find a new and better reporter gene for type 1 IFN than MxA and genes specific for either IFN‐α or ‐β, a micro array screen was carried using the U133A chip from Affymetrix. The expression of 22,000 genes can be studied simultaneous with this technology. The results will be presented at the conference. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169566/ doi: 10.1111/j.0300-9475.2004.01423bb.x id: cord-001109-xs7df6a7 author: Tapia, Karla title: Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity date: 2013-10-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling. We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. Remarkably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing DVGs, while cells within the lung that contain standard viral genomes alone do not express this cytokine. Together, our data indicate that DVGs generated during viral replication are a primary source of danger signals for the initiation of the host immune response to infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814336/ doi: 10.1371/journal.ppat.1003703 id: cord-269734-u43gt8fh author: Teijaro, J.R. title: Pleiotropic Roles of Type 1 Interferons in Antiviral Immune Responses date: 2016-09-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Since Isaac's and Lindenmann's seminal experiments over 50 years ago demonstrating a soluble factor generated from heat killed virus-stimulated chicken embryos could inhibit live influenza virus replication, the term interferon has been synonymous with inhibition of virus replication. While the antiviral properties of type 1 interferon (IFN-I) are undeniable, recent studies have reported expanding and somewhat unexpected roles of IFN-I signaling during both acute and persistent viral infections. IFN-I signaling can promote morbidity and mortality through induction of aberrant inflammatory responses and recruitment of inflammatory innate immune cell populations during acute respiratory viral infections. During persistent viral infection, IFN-I signaling promotes containment of early viral replication/dissemination, however, also initiates and maintains immune suppression, lymphoid tissue disorganization, and CD4 T cell dysfunction through modulation of multiple immune cell populations. Finally, new data are emerging illuminating how specific IFN-I species regulate immune pathology and suppression during acute and persistent viral infections, respectively. Systematic characterization of the cellular populations that produce IFN-I, how the timing of IFN-I induction and intricacies of subtype specific IFN-I signaling promote pathology or immune suppression during acute and persistent viral infections should inform the development of treatments and modalities to control viral associated pathologies. url: https://api.elsevier.com/content/article/pii/S0065277616300372 doi: 10.1016/bs.ai.2016.08.001 id: cord-002248-92pzqj35 author: Terasaki, Kaori title: Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence date: 2016-10-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053439/ doi: 10.1371/journal.pntd.0005047 id: cord-265592-r8nlef0h author: Teuber, G. title: Randomized, placebo‐controlled, double‐blind trial with interferon‐α with and without amantadine sulphate in primary interferon‐α nonresponders with chronic hepatitis C date: 2001-12-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In primary interferon‐α (IFN‐α) nonresponders with chronic hepatitis C, retreatment with IFN‐α has only limited efficacy with sustained response rates below 10%. Therefore, the aims of the present study were to compare the efficacy and safety of IFN‐α alone or in combination with amantadine sulphate in nonresponders to previous IFN‐α monotherapy. Fifty‐five IFN‐α nonresponders with chronic hepatitis C (mean age: 46.6 years) received IFN‐α 6 MIU thrice weekly for 24 weeks followed by 3 MIU thrice weekly for additional 24 weeks. Amantadine sulphate (n=26) or a matched placebo (n=29) was given orally twice daily for 48 weeks. Because of a low initial response rate at week 12 (13/55 patients) and a high breakthrough rate (8/13 patients) after IFN‐α dose reduction in week 24, a virological end‐of‐treatment response with undetectable serum HCV‐RNA (< 1000 copies/mL) was achieved in only five patients (IFN‐α/amantadine sulphate, one patient; IFN‐α/placebo, four patients). After 24 weeks follow‐up a sustained virological response was observed in only two patients receiving IFN‐α and placebo. Health‐related quality‐of‐life analysis showed a substantial improvement of the Profile of Mood States (POMS) scale concerning the subscales fatigue (P < 0.05) and vigor (P < 0.05) in patients receiving combined IFN‐α/amantadine sulphate treatment compared with those treated with IFN‐α alone. IFN‐α/amantadine sulphate combination therapy was well tolerated without any serious adverse events. In conclusion, retreatment with IFN‐α and amantadine sulphate does not increase the low sustained virological response rates of IFN‐α therapy in primary IFN‐α nonresponders with chronic hepatitis C, but may lead to a sustained improvement of health‐related quality‐of‐life. url: https://www.ncbi.nlm.nih.gov/pubmed/11454179/ doi: 10.1046/j.1365-2893.2001.00297.x id: cord-255034-x100xo2t author: Theresine, Maud title: Airway Natural Killer Cells and Bacteria in Health and Disease date: 2020-09-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Natural killer (NK) cells are innate lymphoid cells at the interface between innate and adaptive immunity and mostly studied for their important roles in viral infections and malignant tumors. They can kill diseased cells and produce cytokines and chemokines, thereby shaping the adaptive immune response. Nowadays, NK cells are considered as a strong weapon for cancer immunotherapy and can for example be transduced to express tumor-specific chimeric antigen receptors or harnessed with therapeutic antibodies such as the so-called NK engagers. Whereas a large body of literature exists about the antiviral and antitumoral properties of NK cells, their potential role in bacterial infections is not that well delineated. Furthermore, NK cells are much more heterogeneous than previously thought and have tissue-characteristic features and phenotypes. This review gives an overview of airway NK cells and their position within the immunological army dressed against bacterial infections in the upper and predominantly the lower respiratory tracts. Whereas it appears that in several infections, NK cells play a non-redundant and protective role, they can likewise act as rather detrimental. The use of mouse models and the difficulty of access to human airway tissues for ethical reasons might partly explain the divergent results. However, new methods are appearing that are likely to reduce the heterogeneity between studies and to give a more coherent picture in this field. url: https://doi.org/10.3389/fimmu.2020.585048 doi: 10.3389/fimmu.2020.585048 id: cord-004341-co9s26x1 author: Thukral, Akanksha title: A single dose polyanhydride-based nanovaccine against paratuberculosis infection date: 2020-02-14 words: 6736.0 sentences: 375.0 pages: flesch: 43.0 cache: ./cache/cord-004341-co9s26x1.txt txt: ./txt/cord-004341-co9s26x1.txt summary: Pre-challenge immune responses For Trial I (i.e., safety study), the T cell response was evaluated at 6 weeks post-vaccination by performing IFN-γ ELISA on spleen derived lymphocytes (described in Methods) (Supplemental Fig. 1 ). Post-challenge immune responses To evaluate T cell response in Trial I/safety study IFN-γ ELISA was performed and result of which depicted no significant differences in IFN-γ levels among the groups (Supplemental Fig. 2b ) while at 12 weeks post challenge Mycopar and PAN-lysate vaccinated animals showed significantly higher IFN-γ levels as compared with control animals given PBS (Supplemental Fig. 2c ). At 12 WPC, multiparametric flow cytometry analysis indicated that mice immunized with PAN-Cf elicited a significantly higher percent of antigen specific double cytokine (IFN-γ, TNF-α + ) and single cytokine (IFN-γ) producing CD8 + T cells compared with non-vaccinated and Mycopar® vaccinated mice (Fig. 4 ). abstract: Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) causes Johne’s disease in ruminants and is characterized by chronic gastroenteritis leading to heavy economic losses to the dairy industry worldwide. The currently available vaccine (inactivated bacterin in oil base) is not effective in preventing pathogen shedding and is rarely used to control Johne’s disease in dairy herds. To develop a better vaccine that can prevent the spread of Johne’s disease, we utilized polyanhydride nanoparticles (PAN) to encapsulate mycobacterial antigens composed of whole cell lysate (PAN-Lysate) and culture filtrate (PAN-Cf) of M. paratuberculosis. These nanoparticle-based vaccines (i.e., nanovaccines) were well tolerated in mice causing no inflammatory lesions at the site of injection. Immunological assays demonstrated a substantial increase in the levels of antigen-specific T cell responses post-vaccination in the PAN-Cf vaccinated group as indicated by high percentages of triple cytokine (IFN-γ, IL-2, TNF-α) producing CD8(+) T cells. Following challenge, animals vaccinated with PAN-Cf continued to produce significant levels of double (IFN-γ, TNF-α) and single cytokine (IFN-γ) secreting CD8(+) T cells compared with animals vaccinated with an inactivated vaccine. A significant reduction in bacterial load was observed in multiple organs of animals vaccinated with PAN-Cf, which is a clear indication of protection. Overall, the use of polyanhydride nanovaccines resulted in development of protective and sustained immunity against Johne’s disease, an approach that could be applied to counter other intracellular pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021715/ doi: 10.1038/s41541-020-0164-y id: cord-354620-xf6glr2h author: Tian, Bin title: Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus date: 2020-01-28 words: 8895.0 sentences: 373.0 pages: flesch: 48.0 cache: ./cache/cord-354620-xf6glr2h.txt txt: ./txt/cord-354620-xf6glr2h.txt summary: Our study provided practical methods for isolating and culturing duck primary cells, and our results will facilitate further investigations of organ tropism, innate immune responses, latent infection, and the effectiveness of antiviral drugs for treating DPV and potentially other aerial bird pathogens. In the present study, we isolated five types of duck primary cells [duck embryo fibroblasts (DEFs), neurons, astrocytes, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages] to identify appropriate cell models for DPV, using tropism infection and innate immunologic assays. Upon stimulation with DNA viruses, monocytes/macrophages exhibit higher levels of IFN-β, ISG, and inflammatory cytokine expression than DEFs, neurons, astrocytes, and PBMCs. To elucidate the mechanisms associated with the different responses of the five types of duck primary cells to DNA and RNA virus analogs, the basal levels of innate immune factors were compared. abstract: Duck plague virus (DPV) is a representative pathogen transmitted among aquatic animals that causes gross lesions and immune inhibition in geese and ducks. The mechanism of organ tropism and innate immune evasion of DPV has not been completely deciphered due to a lack of cell models to study the innate immune manipulation and pathogenicity of aquatic viruses. In the present study, we isolated five types of duck primary cells [duck embryo fibroblasts (DEFs), neurons, astrocytes, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages] to identify appropriate cell models for DPV, using tropism infection and innate immunologic assays. Cells responded differently to stimulation with DNA viruses or RNA virus analogs. DPV infection exhibited broad tropism, as the recombinant virulent strain (CHv-GFP) infected DEFs, neurons, astrocytes, and monocytes/macrophages, but not the PBMCs, as the expression of EGFP was negligible. The basal levels of innate immunity molecules were highest in monocytes/macrophages and lower in DEFs and astrocytes. Conversely, the titer and genomic copy number of the attenuated virus strain was higher in DEFs and astrocytes than in neurons and monocytes/macrophages. The titer and genomic copy number of the attenuated virus strain were higher compared with the virulent strain in DEFs, neurons, and astrocytes. The innate immune response was not significantly induced by either DPV strain in DEFs, neurons, or astrocytes. The virulent strain persistently infected monocytes/macrophages, but the attenuated strain did so abortively, and this was accompanied by the phenomenon of innate immune inhibition and activation by the virulent and attenuated strains, respectively. Blockage of IFNAR signaling promoted replication of the attenuated strain. Pre-activation of IFNAR signaling inhibited infection by the virulent strain. The selection assay results indicated that induction of innate immunity plays an essential role in controlling DPV infection, and monocytes/macrophages are an important cell model for further investigations. Our study provided practical methods for isolating and culturing duck primary cells, and our results will facilitate further investigations of organ tropism, innate immune responses, latent infection, and the effectiveness of antiviral drugs for treating DPV and potentially other aerial bird pathogens. url: https://doi.org/10.3389/fimmu.2019.03131 doi: 10.3389/fimmu.2019.03131 id: cord-265005-e6rpryrh author: Tomasello, Elena title: Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types date: 2014-10-30 words: 18082.0 sentences: 948.0 pages: flesch: 40.0 cache: ./cache/cord-265005-e6rpryrh.txt txt: ./txt/cord-265005-e6rpryrh.txt summary: We will discuss the expression patterns and functions of endosomal TLRs with regards to IFN production in uninfected specialized immune cell types, pDCs and XCR1 + DCs. Plasmacytoid DCs uniquely produce very large amounts of IFNs in response to in vitro stimulation with many viruses, without being infected (46) . Under these conditions, to promote health over disease, the benefits for the host of producing high circulating levels of IFNs in order to induce widespread cell-intrinsic anti-viral defenses might prevail over the deleterious effects that this could cause on certain cell types or tissues. Subcapsular sinus macrophages rapidly become infected by viruses incoming from the lymph and produce large amounts of IFNs. This altruistic suicide prevents virus dissemination to other adjacent cell types and promotes the induction of innate and adaptive anti-viral immunity (87) . abstract: Type I interferons (IFN-I) were identified over 50 years ago as cytokines critical for host defense against viral infections. IFN-I promote anti-viral defense through two main mechanisms. First, IFN-I directly reinforce or induce de novo in potentially all cells the expression of effector molecules of intrinsic anti-viral immunity. Second, IFN-I orchestrate innate and adaptive anti-viral immunity. However, IFN-I responses can be deleterious for the host in a number of circumstances, including secondary bacterial or fungal infections, several autoimmune diseases, and, paradoxically, certain chronic viral infections. We will review the proposed nature of protective versus deleterious IFN-I responses in selected diseases. Emphasis will be put on the potentially deleterious functions of IFN-I in human immunodeficiency virus type 1 (HIV-1) infection, and on the respective roles of IFN-I and IFN-III in promoting resolution of hepatitis C virus (HCV) infection. We will then discuss how the balance between beneficial versus deleterious IFN-I responses is modulated by several key parameters including (i) the subtypes and dose of IFN-I produced, (ii) the cell types affected by IFN-I, and (iii) the source and timing of IFN-I production. Finally, we will speculate how integration of this knowledge combined with advanced biochemical manipulation of the activity of the cytokines should allow designing innovative immunotherapeutic treatments in patients. Specifically, we will discuss how induction or blockade of specific IFN-I responses in targeted cell types could promote the beneficial functions of IFN-I and/or dampen their deleterious effects, in a manner adapted to each disease. url: https://www.ncbi.nlm.nih.gov/pubmed/25400632/ doi: 10.3389/fimmu.2014.00526 id: cord-029488-l11ufs6k author: Tomita, Kengo title: Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury date: 2020-07-21 words: 5094.0 sentences: 264.0 pages: flesch: 45.0 cache: ./cache/cord-029488-l11ufs6k.txt txt: ./txt/cord-029488-l11ufs6k.txt summary: Expression levels of VEGF were significantly reduced in lung tissues from mice with both intranasal LPS administration and cecal ligation and puncture (CLP)-induced sepsis, which may stem from decreases in non-endothelial cells-dependent VEGF production in the lungs. In support of this assumption, stimulation with LPS and interferon-γ (IFN-γ) significantly increased VEGF in human pulmonary microvascular endothelial cells (HPMECs) at mRNA and protein levels. Taken together, our results indicate that VEGF can contribute to the development of non-cardiogenic lung edema in sepsis-associated ALI due to increased VEGF secretion from pulmonary vascular endothelial cells through multiple MAPK-dependent pathways. We thus examined whether expression of VEGF in human pulmonary microvascular endothelial cells is regulated by MAPKs. When HPMEC-ST1.6R cells were treated with PD98059, an inhibitor of MAPK kinase which is an ERK1/2 upstream activator, or SB203580, which is widely used as a specific inhibitor of p38 MAPK, the LPS/IFN-γinduced increase in VEGF protein levels was strongly blocked (Fig. 4b) . abstract: Vascular endothelial growth factor (VEGF) is a prime regulator of vascular permeability. Acute lung injury (ALI) is characterized by high-permeability pulmonary edema in addition to refractory hypoxemia and diffuse pulmonary infiltrates. In this study, we examined whether VEGF can be implicated as a pulmonary vascular permeability factor in sepsis-associated ALI. We found that a great increase in lung vascular leak occurred in mice instilled intranasally with lipopolysaccharide (LPS), as assessed by IgM levels in bronchoalveolar lavage fluid. Treatment with the VEGF-neutralizing monoclonal antibody bevacizumab significantly reduced this hyperpermeability response, suggesting active participation of VEGF in non-cardiogenic lung edema associated with LPS-induced ALI. However, this was not solely attributable to excessive levels of intrapulmonary VEGF. Expression levels of VEGF were significantly reduced in lung tissues from mice with both intranasal LPS administration and cecal ligation and puncture (CLP)-induced sepsis, which may stem from decreases in non-endothelial cells-dependent VEGF production in the lungs. In support of this assumption, stimulation with LPS and interferon-γ (IFN-γ) significantly increased VEGF in human pulmonary microvascular endothelial cells (HPMECs) at mRNA and protein levels. Furthermore, a significant rise in plasma VEGF levels was observed in CLP-induced septic mice. The increase in VEGF released from HPMECs after LPS/IFN-γ challenge was completely blocked by either specific inhibitor of mitogen-activated protein kinase (MAPK) subgroups. Taken together, our results indicate that VEGF can contribute to the development of non-cardiogenic lung edema in sepsis-associated ALI due to increased VEGF secretion from pulmonary vascular endothelial cells through multiple MAPK-dependent pathways. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371837/ doi: 10.1007/s00210-020-01947-6 id: cord-348993-8r4fhzlm author: Tomosada, Yohsuke title: Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection date: 2013-08-15 words: 7965.0 sentences: 432.0 pages: flesch: 49.0 cache: ./cache/cord-348993-8r4fhzlm.txt txt: ./txt/cord-348993-8r4fhzlm.txt summary: CONCLUSIONS: The present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Considering this background, the aims of this study were: a) to investigate whether the nasal administration of Lr05 or Lr06 are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to evaluate whether viability of Lr05 or Lr05 is indispensable to modulate respiratory immunity considering that it was reported that heat-killed lactobacilli strains are able to improve lung defenses [11, 15, 16] and; c) to conclusively demonstrate the protective effect of Lr05 and Lr06 by evaluating their capacity to improve the resistance of infant mice against RSV challenge. abstract: BACKGROUND: Some studies have shown that nasally administered immunobiotics had the potential to improve the outcome of influenza virus infection. However, the capacity of immunobiotics to improve protection against respiratory syncytial virus (RSV) infection was not investigated before. OBJECTIVE: The aims of this study were: a) to evaluate whether the nasal administration of Lactobacillus rhamnosus CRL1505 (Lr05) and L. rhamnosus CRL1506 (Lr06) are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to investigate whether viability of Lr05 or Lr06 is indispensable to modulate respiratory immunity and; c) to evaluate the capacity of Lr05 and Lr06 to improve the resistance of infant mice against RSV infection. RESULTS: Nasally administered Lr05 and Lr06 differentially modulated the TLR3/RIG-I-triggered antiviral respiratory immune response. Lr06 administration significantly modulated the production of IFN-α, IFN-β and IL-6 in the response to poly(I:C) challenge, while nasal priming with Lr05 was more effective to improve levels of IFN-γ and IL-10. Both viable Lr05 and Lr06 strains increased the resistance of infant mice to RSV infection while only heat-killed Lr05 showed a protective effect similar to those observed with viable strains. CONCLUSIONS: The present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Comparative studies using two Lactobacillus rhamnosus strains of the same origin and with similar technological properties showed that each strain has an specific immunoregulatory effect in the respiratory tract and that they differentially modulate the immune response after poly(I:C) or RSV challenges, conferring different degree of protection and using distinct immune mechanisms. We also demonstrated in this work that it is possible to beneficially modulate the respiratory defenses against RSV by using heat-killed immunobiotics. url: https://www.ncbi.nlm.nih.gov/pubmed/23947615/ doi: 10.1186/1471-2172-14-40 id: cord-274247-5qiwui6u author: Torrecilhas, A C T title: Interference of natural mouse hepatitis virus infection with cytokine production and susceptibility to Trypanosoma cruzi date: 1999-03-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Mouse hepatitis virus (MHV) infection can have a pronounced impact on several investigation areas. Reports on natural MHV outbreaks are rare and most studies have been conducted by deliberately infecting mice with MHV laboratory strains that cause moderate to severe disturbances to the immune system. We have investigated the effects of a natural acute outbreak of MHV in our otherwise specific-pathogen-free (SPF) inbred mouse colonies, and of enzootic chronic MHV infection on cytokine production and resistance to the intracellular pathogen Trypanosoma cruzi. We found that BALB/c and/or C57BL/6 SPF mice that had been injected with T. cruzi blood trypomastigotes from recently MHV-contaminated (MHV(+)) mice developed significantly higher parasite blood counts, accelerated death, and showed higher IL-10 production by spleen cells than their counterparts whose T. cruzi inoculum was derived from MHV-negative (MHV(−)) donors. Interferon-γ (IFN-γ) production by MHV(+) and MHV(−) mice was not significantly different. In contrast, T. cruzi infection of chronically MHV-infected mice did not result in major changes in the course of infection when compared with that observed in mice from MHV(−) colonies, although a trend to higher parasitaemia levels was observed in BALB/c MHV(+) mice. Nevertheless, both BALB/c and C57BL/6 T. cruzi-infected MHV(+) mice had diminished IFN-γ production to parasite-antigen stimulation in comparison with similarly infected MHV(−) mice. Interleukin-10 (IL-10) production levels by spleen cells did not differ between chronic MHV(+) and MHV(−) mice, but IFN-γ neutralization by monoclonal antibody treatment of anti-CD3-stimulated spleen cell cultures showed higher levels of IL-10 synthesis in MHV(+) BALB/c mice. url: https://www.ncbi.nlm.nih.gov/pubmed/10233719/ doi: 10.1046/j.1365-2567.1999.00719.x id: cord-252950-eiphxwmn author: Trouillet-Assant, Sophie title: Type I IFN immunoprofiling in COVID-19 patients date: 2020-04-29 words: 1555.0 sentences: 118.0 pages: flesch: 53.0 cache: ./cache/cord-252950-eiphxwmn.txt txt: ./txt/cord-252950-eiphxwmn.txt summary: COVID patients in ICU present a high mortality rate and immunoprofiling reveals heterogeneous IFN-α2 production with about 20% of critically-ill patients unable to produce IFN-α2, highlighting the immune response heterogeneity and opening avenues for targeted therapies. 42 Capsule summary: 43 COVID patients in ICU present a high mortality rate and immunoprofiling reveals heterogeneous α2 production with about 20% of critically-ill patients unable to produce IFN-α2, highlighting the 45 immune response heterogeneity and opening avenues for targeted therapies. Various immunosuppressive drugs, including IL-6 blockers or JAK-STAT signaling inhibitors have been 56 suggested for the treatment of SARS-COV-2 infection 2 whereas additional clinical trials are evaluating 57 the use of recombinant interferon to foster host antiviral response. To date, IFN-I response has not been evaluated in COVID-19 60 patients and its contribution to the viral control and inflammation is unknown. We further explored a larger cohort of 26 critically ill COVID patients from one of the intensive care 75 unit (ICU) at Hospices Civils de Lyon (Lyon, France). abstract: COVID patients in ICU present a high mortality rate and immunoprofiling reveals heterogeneous IFN-α2 production with about 20% of critically-ill patients unable to produce IFN-α2, highlighting the immune response heterogeneity and opening avenues for targeted therapies. url: https://doi.org/10.1016/j.jaci.2020.04.029 doi: 10.1016/j.jaci.2020.04.029 id: cord-270498-hh6h50t2 author: Tseng, Chin-Kai title: Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells date: 2017-09-19 words: 4954.0 sentences: 277.0 pages: flesch: 47.0 cache: ./cache/cord-270498-hh6h50t2.txt txt: ./txt/cord-270498-hh6h50t2.txt summary: Celastrol-induced heme oxygenase 1 (HO-1) expression promoted antiviral interferon responses and inhibition of NS3/4A protease activity, thereby blocking HCV replication. These antiviral effects were abrogated by treatment with the HO-1-specific inhibitor SnMP or silencing of HO-1 expression by transfection of shRNA, which indicates that HO-1 induction contributes to the anti-HCV activity of celastrol. In this study, our data revealed that celastrol significantly inhibits HCV replication, and that the anti-HCV effect of celastrol was attenuated by the HO-1 specific inhibitor tin mesoporphyrin (SnMP) or HO-1 gene expression silencing. Celastrol-mediated HO-1 induction contributed to the anti-HCV action through inducing antiviral IFN response and inhibiting HCV NS3 protease activity. As shown in Fig. 7B , HO-1 RNA expression levels were induced by celastrol compared with non-celastrol treated cells and the JNK inhibitor SP600125 significantly reduced the HO-1 inductive effect of celastrol. In the present study, we found that a natural product celastrol could effectively inhibit HCV NS3/4A protease activity and enhance IFN-mediated antiviral gene expression through HO-1 induction (Figs. abstract: BACKGROUND AND PURPOSE: Celastrol, a quinone methide triterpene isolated from the root extracts of Tripterygium wilfordii, can greatly induce the gene expression activity of heme oxygenase-1 (HO-1) to achieve disease prevention and control. HO-1 induction was recently shown to result in anti-HCV activity by inducing type I interferon and inhibiting hepatitis C virus (HCV) NS3/4A protease activity. The aim of the present study is to evaluate the anti-HCV activity of celastrol and characterize its mechanism of inhibition. METHODS: The anti-HCV activity of celastrol was evaluated using the HCV subgenomic replicon and HCVcc infection systems. The anti-HCV mechanism of celastrol targeting HO-1 expression was clarified using specific inhibitors against several signaling pathways. The transcriptional regulation of celastrol on target gene expression was determined using promoter-based reporter activity assay. The synergistic effect of celastrol and a numbers of clinically used anti-HCV drugs was determined via a drug combination assay. RESULTS: Celastrol inhibited HCV replication in both the HCV subgenomic and HCVcc infection systems with EC50 values of 0.37 ± 0.022 and 0.43 ± 0.019 μM, respectively. Celastrol-induced heme oxygenase 1 (HO-1) expression promoted antiviral interferon responses and inhibition of NS3/4A protease activity, thereby blocking HCV replication. These antiviral effects were abrogated by treatment with the HO-1-specific inhibitor SnMP or silencing of HO-1 expression by transfection of shRNA, which indicates that HO-1 induction contributes to the anti-HCV activity of celastrol. JNK mitogen-activated protein kinase and nuclear factor erythroid 2-related factor 2 (Nrf2) were confirmed to be involved in the inductive effect of celastrol on HO-1 expression. Celastrol exhibited synergistic effects in combination with interferon-alpha, the NS5A inhibitor daclatasvir, and the NS5B inhibitor sofosbuvir. CONCLUSION: Celastrol can serve as a potential supplement for blocking HCV replication. Targeting the JNK/Nrf2/HO-1 axis presents a promising strategy against HCV infection. url: https://doi.org/10.1016/j.antiviral.2017.09.010 doi: 10.1016/j.antiviral.2017.09.010 id: cord-321050-yabt72jf author: Tuttle, Kathryn D. title: JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy date: 2020-04-09 words: 4121.0 sentences: 208.0 pages: flesch: 46.0 cache: ./cache/cord-321050-yabt72jf.txt txt: ./txt/cord-321050-yabt72jf.txt summary: Increasing evidence supports the notion that mortality during infections with SARS-CoV-2, which causes coronavirus disease of 2019 , is driven by the exacerbated immune response to the virus, leading to a cascade of events involving a cytokine storm and acute respiratory distress syndrome (ARDS), often accompanied by myocardial damage and multiple organ failure (5, 6) . Overall, these results have potential far-reaching significance for the treatment of COVID-19, justifying a deeper study of JAK inhibitors as a therapeutic strategy to attenuate the cytokine storm and downstream organ failure in this condition, while also indicating that individuals with DS should be considered a high-risk population during the COVID-19 pandemic. This analysis revealed that Dp16 mice have increased liver pathology even before P(I:C) treatment, as demonstrated by significantly higher levels of cell injury, inflammation, and reactive changes relative to their WT littermates (Figure 4B,C) . abstract: Cytokine storms are drivers of pathology and mortality in myriad viral infections affecting the human population. In SARS-CoV-2-infected patients, the strength of the cytokine storm has been associated with increased risk of acute respiratory distress syndrome, myocardial damage, and death. However, the therapeutic value of attenuating the cytokine storm in COVID-19 remains to be defined. Here, we report results obtained using a novel mouse model of lethal sterile anti-viral immune responses. Using a mouse model of Down syndrome (DS) with a segmental duplication of a genomic region encoding four of the six interferon receptor genes (Ifnrs), we demonstrate that these animals overexpress Ifnrs and are hypersensitive to IFN stimulation. When challenged with viral mimetics that activate Toll-like receptor signaling and IFN anti-viral responses, these animals overproduce key cytokines, show exacerbated liver pathology, rapidly lose weight, and die. Importantly, the lethal immune hypersensitivity, accompanying cytokine storm, and liver hyperinflammation are blocked by treatment with a JAK1-specific inhibitor. Therefore, these results point to JAK1 inhibition as a potential strategy for attenuating the cytokine storm and consequent organ failure during overdrive immune responses. Additionally, these results indicate that people with DS, who carry an extra copy of the IFNR gene cluster encoded on chromosome 21, should be considered at high risk during the COVID-19 pandemic. One Sentence Summary Inhibition of the JAK1 kinase prevents pathology and mortality caused by a rampant innate immune response in mice. url: https://doi.org/10.1101/2020.04.07.024455 doi: 10.1101/2020.04.07.024455 id: cord-001868-utsvsja0 author: Uematsu, Takayuki title: Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity date: 2015-12-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667252/ doi: 10.1038/srep17577 id: cord-023391-bq5w3jk9 author: Utermöhlen, O. title: Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes date: 2008-06-28 words: 16856.0 sentences: 870.0 pages: flesch: 46.0 cache: ./cache/cord-023391-bq5w3jk9.txt txt: ./txt/cord-023391-bq5w3jk9.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: The phagolysosomally localized acid sphingomyelinase (ASMase) activated by proinflammatory cytokines such as TNF and IFN‐γ generates the signalling molecule ceramide which in turn results in the activation of proteases like cathepsin D. These characteristics of ASMase suggest a possible role of this molecule in the phagocytotic uptake and phagosomal degradation processes of antigens or in antigen presentation. We show here that ASMase(–/–) mice fail to eliminate the noncytopathic lymphocytic choriomeningitis (LCM) virus as rapidly as littermate wildtype mice. Investigation of the immune response revealed a reduced expansion of CD8(+) T cells. The secretion of IFN‐γ in response to contact with target cells as well as the cytolytic activity of virus‐specific CD8(+) T cells was severely impaired. Additionally, both phases of the LCM virus‐specific DTH response, mediated by CD8(+) and CD4(+) T cells consecutively, were diminished in ASMase(–/–) mice. However, the secondary memory response of virus‐specific CTL was not altered, and the virus was effectively controlled for at least 3 months by ASMase(–/–) mice. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus‐specific CD8(+) T cells during the acute infection of mice with the LCM virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169516/ doi: 10.1111/j.0300-9475.2004.01423l.x id: cord-253077-61fmul8c author: Vabret, Nicolas title: Immunology of COVID-19: current state of the science date: 2020-05-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection. url: https://www.ncbi.nlm.nih.gov/pubmed/32505227/ doi: 10.1016/j.immuni.2020.05.002 id: cord-323756-atnrw9ew author: Vabret, Nicolas title: Sensing Microbial RNA in the Cytosol date: 2013-12-25 words: 6409.0 sentences: 355.0 pages: flesch: 45.0 cache: ./cache/cord-323756-atnrw9ew.txt txt: ./txt/cord-323756-atnrw9ew.txt summary: When Janeway formulated the theory of pattern recognition in 1989, he proposed that host cells could sense microbial infection owing to receptors able to recognize invariant molecular structures defined as pathogen-associated molecular patterns (PAMPs). They share a similar organization with three distinct domains: (i) a C-terminal repressor domain (RD) embedded within the C-terminal domain (CTD); (ii) a central ATPase containing DExD/H-box helicase domain able to bind RNA; and (iii) a N-terminal tandem CARD domain that mediates downstream signaling, and which is present in RIG-I and MDA5 but absent in LGP2. DDX60 has also been shown to enhance the IFN-I response to RNA and DNA stimulation through formation of complexes with Frontiers in Immunology | Molecular Innate Immunity RIG-I, MDA5, and LGP2 but not with MAVS. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses abstract: The innate immune system faces the difficult task of keeping a fine balance between sensitive detection of microbial presence and avoidance of autoimmunity. To this aim, key mechanisms of innate responses rely on isolation of pathogens in specialized subcellular compartments, or sensing of specific microbial patterns absent from the host. Efficient detection of foreign RNA in the cytosol requires an additional layer of complexity from the immune system. In this particular case, innate sensors should be able to distinguish self and non-self molecules that share several similar properties. In this review, we discuss this interplay between cytosolic pattern recognition receptors and the microbial RNA they detect. We describe how microbial RNAs gain access to the cytosol, which receptors they activate and counter-strategies developed by microorganisms to avoid this response. url: https://www.ncbi.nlm.nih.gov/pubmed/24400006/ doi: 10.3389/fimmu.2013.00468 id: cord-295781-b831y105 author: VanLeuven, James T. title: Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses date: 2017-06-02 words: 7213.0 sentences: 363.0 pages: flesch: 52.0 cache: ./cache/cord-295781-b831y105.txt txt: ./txt/cord-295781-b831y105.txt summary: title: Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. While these models are invaluable for evaluating pathology and host responses to infection, parallel in vitro studies can be used to identify gene expression and signaling pathway changes that occur in infected cells to mediate pathogenesis. In this study, we compare the gene expression response of murine lung epithelial cells to infection by three respiratory viruses used in murine models: rhinovirus (serotype RV1B) in the family Picornaviridae, mouse hepatitis virus (MHV strain 1) in the family Coronaviridae, and influenza A virus (strain PR8) in the family Orthomyxoviridae. abstract: The severity of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to viruses from different families while controlling other experimental parameters. Murine models are commonly used to study the pathogenesis of respiratory viral infections, and in vitro studies using murine cells provide mechanistic insight into the pathogenesis observed in vivo. We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to distinguish shared and virus-specific mechanisms of pathogenesis in the respiratory tract. url: https://www.ncbi.nlm.nih.gov/pubmed/28575086/ doi: 10.1371/journal.pone.0178408 id: cord-004685-qote5nx2 author: Vassão, R. C. title: A genetic analysis of macrophage activation and specific antibodies in relation to the resistance of heterogeneous mouse populations to MHV3 infection date: 1994 words: 2352.0 sentences: 113.0 pages: flesch: 42.0 cache: ./cache/cord-004685-qote5nx2.txt txt: ./txt/cord-004685-qote5nx2.txt summary: The data indicate, among the mechanisms of resistance against the virus infection, a role of IFN gamma macrophage-activation and of antibodies against MHV3 which may delay the mean survival time in susceptible animals. The virus replication in target cells, the antiviral state induced by interferon (IFN) and the expression of a monokine with procoagulant activity (PCA) have been implicated in the resistance/susceptibility of the genetic homogeneous or heterogeneous mouse populations to the MHV3 infection [t, 2, 4, 7, 17, 18, 23, 243 . For the study of the individual correlation between in vivo resistance and in vitro inhibition of virus replication by IFN gamma, peritoneal macrophages from Hm, Lm and F 2 segregants were collected without sacrificing the animals, which were infected with MHV3 a week later. This brings further support to our previous suggestion that one of the main mechanisms involved in the resistance of mice to the MHV3 infection is based on the ability of their macrophages to restrict the virus replication upon IFN gamma activation [10 13, 153 . abstract: The genetically selected high antibody responder mice (H(III)) are susceptible and the low antibody responder mice (L(III)) are resistant to the experimental infection with Mouse Hepatitis Virus 3 (MHV3). The mortality rates of the F(1) hybrids and of the F(2) segregants showed the codominance of the susceptible and resistant characters. The direct individual intrapopulation correlation between the induction of antiviral state in macrophages activated by IFN gamma and the resistance to the virus infection, showed that an antiviral state could be induced in resistant mouse macrophages, whereas in susceptible mouse macrophages no restriction of virus replication could be observed. A direct inter- and intrapopulation correlation of pre-existing antibody titres against MHV3 with the mortality and a direct interpopulation correlation of those titres with the mean survival time of susceptible animals was shown. The data indicate, among the mechanisms of resistance against the virus infection, a role of IFN gamma macrophage-activation and of antibodies against MHV3 which may delay the mean survival time in susceptible animals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086603/ doi: 10.1007/bf01310802 id: cord-261028-sxux2ujo author: Vatner, Ralph E. title: STING, DCs and the link between innate and adaptive tumor immunity date: 2017-12-20 words: 10018.0 sentences: 475.0 pages: flesch: 44.0 cache: ./cache/cord-261028-sxux2ujo.txt txt: ./txt/cord-261028-sxux2ujo.txt summary: Dendritic cells (DCs) are a heterogeneous population of professional antigen-presenting cells (APCs) from hematopoietic origin that serve as a key link between the innate and adaptive immune systems, and are the lynchpin in generating anti-tumor immunity (Steinman and Idoyaga, 2010) . More recently, type I IFN production and signaling through the STING pathway has been identified as having an essential role in the development of anti-tumor immunity in response to tumor derived DNA. DNA sensing by STING is the upstream link that triggers type I IFN production by DCs and facilitates effective cross-priming of tumor specific CD8+ T cells. This DNA is likely derived from stressed and dying cancer cells, and is introduced into the DC cytosol through a yet unknown mechanism where it binds to cGAS, which initiates STING mediated type I IFN transcription (Fig. 2) . abstract: Cancer and the immune system are intimately related. Much of the bulk of tumors is comprised of stromal leukocytes with immune functions, which serve to both promote and inhibit tumor growth, invasion and metastasis. The T lymphocytes of the adaptive immune system are essential for tumor immunity, and these T cells are generated by cross-priming against tumor associated antigens. Dendritic cells (DCs) are essential in this process, serving as the cellular link between innate and adaptive immunity. As a prerequisite for priming of adaptive immune responses, DCs must take up tumor antigens, process them and present them in the context of the major histocompatibility complex (MHC). DCs also serve as sensors of innate activation signals from cancer that are necessary for their activation and effective priming of cancer specific T cells. Here we discuss the role of DCs in the sensing of cancer and in priming the adaptive response against tumors. Furthermore, we present the essential role of the Stimulator of Interferon Genes (STING) signaling pathway in producing type I interferons (IFNs) that are essential in this process. url: https://doi.org/10.1016/j.molimm.2017.12.001 doi: 10.1016/j.molimm.2017.12.001 id: cord-007621-rapinodd author: Vidovic, Maria title: Induction and regulation of class II major histocompatibility complex mRNA expression in astrocytes by interferon-γ and tumor necrosis factor-α date: 2002-11-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Astrocytes can function as antigen-presenting cells (APC) upon expression of class II major histocompatibility complex (MHC) antigens, which are induced by interferon-γ (IFN-γ). Previous data from this laboratory had shown that the cytokine tumor necrosis factor-α (TNF-α) enhances IFN-γ-mediated class II antigen expression on astrocytes. We have now investigated the effect of IFN-γ and TNF-α on class II MHC mRNA expression in astrocytes using Northern blot analysis. Astrocytes do not constitutively express mRNA for class II MHC. Kinetic analysis of class II MHC mRNA expression in IFN-γ-treated cells demonstrated an 8 h time lag, which was followed by an increase over the next 16 h. Optimal expression of class II mRNA was detected after a 24 h incubation with IFN-γ. This level of expression was further enhanced by the simultaneous addition of IFN-γ and TNF-α to the astrocytes, while TNF-α alone had no effect on class II mRNA expression. TNF-α does not act by increasing the stability of IFN-γ-induced class II mRNA, indicating its action is not at that specific level of post-transcriptional control. Furthermore, astrocyte class II mRNA expression was inhibited when cycloheximide (CHX) was added together with IFN-γ or IFN-γ/TNF-α, and when CHX was added up to 4 h after treatment with IFN-γ or IFN-γ/TNF-α. These results indicate that astrocyte class II mRNA expression is mediated by newly synthesized proteins induced by IFN-γ and/or IFN-γ/TNF-α. The expression of class II antigens on astrocytes, and cytokine modulation of their expression, may be important in the initiation and perpetuation of intracerebral immune responses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119667/ doi: 10.1016/0165-5728(90)90103-t id: cord-023417-by18aczt author: Vilhelmsson, M. title: The Malassezia sympodialis Allergen Mala s 11 with Sequence Similarity to Manganese Superoxide Dismutase Induces Maturation and Production of Inflammatory Cytokines in Human Dendritic Cells date: 2008-06-28 words: 16931.0 sentences: 868.0 pages: flesch: 46.0 cache: ./cache/cord-023417-by18aczt.txt txt: ./txt/cord-023417-by18aczt.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: The chronic inflammatory skin disease atopic eczema (AE) affects almost 15% of the population in many countries today. The pathogenesis of AE is not fully understood. A combination of genetic predisposition and environmental factors like microorganisms seems to contribute to the symptoms. The yeast Malassezia sympodialis is part of our normal skin micro flora but can act as an allergen and elicit specific IgE and T‐cell reactivity in patients with AE. Recently, we identified a novel major M. sympodialis allergen, designated Mala s 11 (22.4 kDa), with sequence similarity to the mitochondrial enzyme manganese superoxide dismutase (MnSOD). Interestingly, Mala s 11 has a high degree of homology to human MnSOD. The aim of this study was to examine the effects of recombinant Mala s 11 on antigen‐presenting dendritic cells. Monocyte‐derived dendritic cells (MDDCs) from healthy blood donors were cultured with or without Mala s 11 for different time periods. It was found that the maturation marker CD83 and the costimulatory molecules CD80 and CD86 were upregulated on the MDDCs exposed to Mala s 11 for 24 h, as demonstrated by flow cytometry. Furthermore, coculture of MDDCs with Mala s 11 for 9 h induced an increased production of the inflammatory cytokines IL‐6 (200‐fold), TNF‐α (100‐fold) and IL‐8 (sixfold), as detected by the cytometric bead array (CBA) analysis. Our results suggest that Mala s 11 affects the immune response through DC maturation and production of inflammatory cytokines. The potential cross‐reactivity with human MnSOD needs to be explored and the exact role of Mala s 11 in the pathogenesis of AE assessed in clinical studies involving skin prick and atopy patch tests. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169559/ doi: 10.1111/j.0300-9475.2004.01423ae.x id: cord-344798-q34j4zxu author: Villalba, María Caridad Montalvo title: Interferon gamma, TGF-β1 and RANTES expression in upper airway samples from SARS-CoV-2 infected patients date: 2020-08-29 words: 4141.0 sentences: 232.0 pages: flesch: 44.0 cache: ./cache/cord-344798-q34j4zxu.txt txt: ./txt/cord-344798-q34j4zxu.txt summary: title: Interferon gamma, TGF-β1 and RANTES expression in upper airway samples from SARS-CoV-2 infected patients The aim of this study was evaluate inflammatory response using the expression of immune mediators with antiviral, immunosuppression and chemotactic functions in the primary site of SARS-CoV-2 replication, at early stage of infection. J o u r n a l P r e -p r o o f Taking into account that Ct value has a correlation with the amount of RNA present in the samples, it was found that medians and IQR of SARS-CoV-2 viral titer was similar in asymptomatic (33.00, 29.00-37.00) and symptomatic (30, 27 .00-37.00) cases; and comparison between groups did not show difference (p=0.4373). As show our results, SARS-CoV-2 infection induced high IFN-γ expression in swabbed cells from upper airway; its expression was higher in symptomatic patients in comparison with asymptomatic individuals. Also, positive correlation between IFN-γ and TGF-β1 provided evidence of immune response control could determinate the asymptomatic presentation of SARS-CoV-2 infection. abstract: Upper respiratory tract is the primary site of SARS-CoV-2 replication. Releasing of pro and anti-inflammatory mediators plays an important role in the immunopathogenesis of Coronavirus Disease 2019 (COVID-19). The aim of this study was to evaluate the early inflammatory response in upper airway by measuring of IFN-γ, TGF-β1 and RANTES at mRNA level. Forty five SARS-CoV-2 infected patients were enrolled, whose were divided in two groups: asymptomatic and symptomatic. Twenty healthy persons, SARS-CoV-2 negative were included as controls. Higher IFN-γ expression was detected in SARS-CoV-2 infected patients in comparison with controls (p = 0,0393). IFN-γ expression was increased in symptomatic patients (p = 0,0165). TGF-β1 and RANTES expressions were lower in SARS-CoV-2 infected patients than controls (p < 0,0001; p = 0,0011, respectively). A significant correlation between IFN-γ and TGF-β1 was observed in SARS-CoV-2 asymptomatic patients (r = +0,61, p = 0,0014). The findings suggest that imbalance between IFN-γ and TGF-β1 expression could be an impact in clinical expression of SARS-CoV-2 infection. url: https://api.elsevier.com/content/article/pii/S1521661620307361 doi: 10.1016/j.clim.2020.108576 id: cord-353337-o302vxqm author: Visser, Linda J. title: Dissecting distinct proteolytic activities of FMDV L(pro) implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression date: 2020-07-15 words: 9547.0 sentences: 514.0 pages: flesch: 54.0 cache: ./cache/cord-353337-o302vxqm.txt txt: ./txt/cord-353337-o302vxqm.txt summary: To study the effects of L pro on the induction of type I IFN in picornavirus-infected cells, we used two previously generated recombinant viruses; EMCV-L Zn , which contains inactivating mutations in the zinc-finger domain of the Leader (i.e. EMCV''s RLR signaling antagonist) [1, 43, 44] , and EMCV-L pro , which was derived from EMCV-L Zn and additionally encodes FMDV L pro at the N-terminus of its polyprotein ( Fig 1A) [45]. Cleavage of RLR signaling proteins by FMDV L pro correlates with type I IFN suppression degradation of NF-κB p65 and DUB activity as well as to impair L pro ''s ability to reduce IFN-β mRNA expression [36, 39] , also affected L pro ''s ability to cleave MAVS and TBK1. Notably, infection with EMCV L pro L143A, which displayed wt deISGylase/DUB activity but is strongly impaired in its ability to cleave/degrade RLR signaling proteins MAVS, TBK1 and NFκB p65, failed to suppress the induction of IFN-β mRNA. abstract: The type I interferon response is an important innate antiviral pathway. Recognition of viral RNA by RIG-I-like receptors (RLRs) activates a signaling cascade that leads to type I interferon (IFN-α/β) gene transcription. Multiple proteins in this signaling pathway (e.g. RIG-I, MDA5, MAVS, TBK1, IRF3) are regulated by (de)ubiquitination events. Most viruses have evolved mechanisms to counter this antiviral response. The leader protease (L(pro)) of foot-and-mouth-disease virus (FMDV) has been recognized to reduce IFN-α/β gene transcription; however, the exact mechanism is unknown. The proteolytic activity of L(pro) is vital for releasing itself from the viral polyprotein and for cleaving and degrading specific host cell proteins, such as eIF4G and NF-κB. In addition, L(pro) has been demonstrated to have deubiquitination/deISGylation activity. L(pro)’s deubiquitination/deISGylation activity and the cleavage/degradation of signaling proteins have both been postulated to be important for reduced IFN-α/β gene transcription. Here, we demonstrate that TBK1, the kinase that phosphorylates and activates the transcription factor IRF3, is cleaved by L(pro) in FMDV-infected cells as well as in cells infected with a recombinant EMCV expressing L(pro). In vitro cleavage experiments revealed that L(pro) cleaves TBK1 at residues 692–694. We also observed cleavage of MAVS in HeLa cells infected with EMCV-L(pro), but only observed decreasing levels of MAVS in FMDV-infected porcine LFPK αVβ6 cells. We set out to dissect L(pro)’s ability to cleave RLR signaling proteins from its deubiquitination/deISGylation activity to determine their relative contributions to the reduction of IFN-α/β gene transcription. The introduction of specific mutations, of which several were based on the recently published structure of L(pro) in complex with ISG15, allowed us to identify specific amino acid substitutions that separate the different proteolytic activities of L(pro). Characterization of the effects of these mutations revealed that L(pro)’s ability to cleave RLR signaling proteins but not its deubiquitination/deISGylation activity correlates with the reduced IFN-β gene transcription. url: https://www.ncbi.nlm.nih.gov/pubmed/32667958/ doi: 10.1371/journal.ppat.1008702 id: cord-005077-ejgzfzd2 author: Vogel, Wolfgang title: Treatment of chronic hepatitis C patients not responding to combination therapy with ribavirin and interferon α — hype or hope? date: 2004 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088274/ doi: 10.1007/bf03217702 id: cord-297776-k38jssr0 author: Volk, Aaron title: Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages date: 2020-05-18 words: 5843.0 sentences: 293.0 pages: flesch: 42.0 cache: ./cache/cord-297776-k38jssr0.txt txt: ./txt/cord-297776-k38jssr0.txt summary: gene expression, we report significant transcriptional upregulation of multiple genes associated with activation of ER sensors IRE1, ATF6, and PERK, such as Edem1, Hspa5 (encoding BiP protein), and Ddit3 (encoding CHOP), in response to virus replication, with the most robust response detected in cells infected with the wild-type or DUBmut virus infection (Fig. 5B, C, and D) . Overall, these differential gene expression analyses in macrophages reveal similar host responses to the wild-type and DUBmut viruses that include activation of UPR pathways and proinflammatory genes, whereas a distinct transcriptional profile during infection with the EndoUmut virus is predominately defined by a focused, robust antiviral response. The results presented here, and from studies of the MERS-CoV dORF3-5 mutant virus (26) Upon infection of a BMDM with EndoUmut, host double-stranded RNA (dsRNA) sensors (including MDA5, PKR, and OAS) are activated, resulting in robust transcription of type I IFN genes and rapid induction of apoptosis, the latter of which precludes the development of a potent inflammatory response. abstract: Coronaviruses (CoVs) encode multiple interferon (IFN) antagonists that modulate the host response to virus replication. Here, we evaluated the host transcriptional response to infection with murine coronaviruses encoding independent mutations in one of two different viral antagonists, the deubiquitinase (DUB) within nonstructural protein 3 or the endoribonuclease (EndoU) within nonstructural protein 15. We used transcriptomics approaches to compare the scope and kinetics of the host response to the wild-type (WT), DUBmut, and EndoUmut viruses in infected macrophages. We found that the EndoUmut virus activates a focused response that predominantly involves type I interferons and interferon-related genes, whereas the WT and DUBmut viruses more broadly stimulate upregulation of over 2,800 genes, including networks associated with activating the unfolded protein response (UPR) and the proinflammatory response associated with viral pathogenesis. This study highlights the role of viral interferon antagonists in shaping the kinetics and magnitude of the host response during virus infection and demonstrates that inactivating a dominant viral antagonist, the coronavirus endoribonuclease, dramatically alters the host response in macrophages. IMPORTANCE Macrophages are an important cell type during coronavirus infections because they “notice” the infection and respond by inducing type I interferons, which limits virus replication. In turn, coronaviruses encode proteins that mitigate the cell’s ability to signal an interferon response. Here, we evaluated the host macrophage response to two independent mutant coronaviruses, one with reduced deubiquitinating activity (DUBmut) and the other containing an inactivated endoribonuclease (EndoUmut). We observed a rapid, robust, and focused response to the EndoUmut virus, which was characterized by enhanced expression of interferon and interferon-related genes. In contrast, wild-type virus and the DUBmut virus elicited a more limited interferon response and ultimately activated over 2,800 genes, including players in the unfolded protein response and proinflammatory pathways associated with progression of significant disease. This study reveals that EndoU activity substantially contributes to the ability of coronaviruses to evade the host innate response and to replicate in macrophages. url: https://www.ncbi.nlm.nih.gov/pubmed/32188729/ doi: 10.1128/jvi.00178-20 id: cord-323713-bc00vths author: Volpi, Stefano title: Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome date: 2019-05-29 words: 3225.0 sentences: 192.0 pages: flesch: 46.0 cache: ./cache/cord-323713-bc00vths.txt txt: ./txt/cord-323713-bc00vths.txt summary: RESULTS: We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Stimulator of IFN genes (STING)-associated vasculopathy with onset in infancy (SAVI) is caused by gain of function mutations in TMEM173 [3] , which lead to a constitutive production of high levels of type I IFNs without infectious triggers [3] [4] [5] . Notably, the clinical responses did not correlate with decreased type I IFN signatures, which improved only transiently in P1 during concomitant treatment with high dose steroids and ruxolitinib (Fig. 2b) . P3 (follow-up of 12 months) after ten months on treatment on ruxolitinib presented clinical and radiological relapse of lung disease requiring glucocorticoid therapy (2 mg/kg/day of prednisone) with a prompt response (Fig. 2a) . abstract: OBJECTIVES: Mutations affecting the TMEM173 gene cause STING-associated vasculopathy with onset in infancy (SAVI). No standard immunosuppressive treatment approach is able to control disease progression in patients with SAVI. We studied the efficacy and safety of targeting type I IFN signaling with the Janus kinase inhibitor, ruxolitinib. METHODS: We used DNA sequencing to identify mutations in TMEM173 in patients with peripheral blood type I IFN signature. The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis. RESULTS: We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Indirect echocardiographic signs of pulmonary hypertension were present in one case. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Efficacy was persistent in one patient and only transitory in the other two patients. Clinical control of skin complications was obtained, and one patient discontinued steroid treatment. One patient, who presented with kidney involvement, showed resolution of hematuria. One patient experienced increased recurrence of severe viral respiratory infections. Monitoring of peripheral blood type I interferon signature during ruxolitinib treatment did not show a stable decrease. CONCLUSIONS: We conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-019-00645-0) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/31144250/ doi: 10.1007/s10875-019-00645-0 id: cord-259748-x7dq1sy4 author: Wan, Dongshan title: Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response date: 2020-04-28 words: 14147.0 sentences: 850.0 pages: flesch: 41.0 cache: ./cache/cord-259748-x7dq1sy4.txt txt: ./txt/cord-259748-x7dq1sy4.txt summary: Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immune-surveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. In 2008, several research teams discovered a new protein on the endoplasmic reticulum (ER) which can be activated by immune-stimulatory DNA (ISD) and initiate type-I interferon (IFN) responses, which was named "stimulator of interferon genes" (STING, also known as MITA, ERIS) (2) (3) (4) . Mitochondrial outer membrane permeabilization (MOMP) activation, which is executed by BCL-2-associated X protein (BAX) and BCL-2 antagonist or killer (BAK), is a highly controlled conserved process in regulated cell FIGURE 3 | Interaction of the cGAS-STING pathway with other DNA-sensing pathways and its role in cell survival. Human plasmacytoid dentritic cells elicit a Type I interferon response by sensing DNA via the cGAS-STING signaling pathway abstract: Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immune-surveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. cGAS-STING pathway interplays with other innate immune pathways, by which it participates in regulating infection, inflammatory disease, and cancer. The therapeutic approaches targeting this pathway show promise for future translation into clinical applications. Here, we present a review of the important previous works and recent advances regarding the cGAS-STING pathway, and provide a comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states. url: https://www.ncbi.nlm.nih.gov/pubmed/32411126/ doi: 10.3389/fimmu.2020.00615 id: cord-305263-fgwf6wy3 author: Wang, Ben X. title: The yin and yang of viruses and interferons date: 2012-02-07 words: 6285.0 sentences: 294.0 pages: flesch: 38.0 cache: ./cache/cord-305263-fgwf6wy3.txt txt: ./txt/cord-305263-fgwf6wy3.txt summary: IFN therapy therefore has the advantage over DAA treatments in that, in addition to stimulating genes that block viral replication in infected cells, IFNs activate other innate and adaptive immune responses to combat the virus. For example, polymorphisms in host genes encoding proteins associated with regulation of an IFN response such as interferon receptor a-chain (IFNAR1) [10] , the IFN-inducible myxovirus resistance GTPase protein, Mx [11] , the IFN-inducible 2 0 ,5 0 -oligoadenylate synthetase (OAS) [12] and the suppressor of cytokine signaling (SOCS) 3 associated with regulation of an IFN response [13] , are predictive markers linked with the rate of sustained virological response (SVR) to HCV infection following IFN-a treatment. Remarkably, distinct highly pathogenic respiratory viruses, namely influenza viruses and the SARS-CoV, encode nonstructural proteins in their genomes that function as virulence factors that specifically target the host innate IFN response, further emphasizing the importance of IFNs as broad-spectrum antivirals. abstract: Interferons (IFNs)-α/β are critical effectors of the innate immune response to virus infections. Through activation of the IFN-α/β receptor (IFNAR), they induce expression of IFN-stimulated genes (ISGs) that encode antiviral proteins capable of suppressing viral replication and promoting viral clearance. Many highly pathogenic viruses have evolved mechanisms to evade an IFN response and the balance between the robustness of the host immune response and viral antagonistic mechanisms determines whether or not the virus is cleared. Here, we discuss IFNs as broad-spectrum antivirals for treatment of acute virus infections. In particular, they are useful for treatment of re-emerging virus infections, where direct-acting antivirals (DAAs) have limited utility due to DAA-resistant mutations, and for newly emerging virus strains in which the time to vaccine availability precludes vaccination at the onset of an outbreak. url: https://doi.org/10.1016/j.it.2012.01.004 doi: 10.1016/j.it.2012.01.004 id: cord-252772-f3fctcru author: Wang, Changlin title: The Coronavirus PEDV Evades Type III Interferon Response Through the miR-30c-5p/SOCS1 Axis date: 2020-05-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine epidemic diarrhea virus (PEDV) is an economically important pathogen that has evolved several mechanisms to evade type I IFN responses. Type III interferon (IFN-λ), an innate cytokine that primarily targets the mucosal epithelia, is critical in fighting mucosal infection in the host and has been reported to potently inhibit PEDV infection in vitro. However, how PEDV escapes IFN-λ antiviral response remains unclear. In this study, we found that PEDV infection induced significant IFN-λ expression in type I IFN-defective Vero E6 cells, but virus-induced endogenous IFN-λ did not reduce PEDV titers. Moreover, we demonstrated that PEDV escaped IFN-λ responses by substantially upregulating the suppressor of cytokine signaling protein 1 (SOCS1) expression, which impaired the induction of IFN-stimulated genes (ISGs) and dampened the IFN-λ antiviral response and facilitated PEDV replication in Vero E6 cells. We further showed that PEDV infection increased SOCS1 expression by decreasing host miR-30c-5p expression. MiR-30c-5p suppressed SOCS1 expression through targeting the 3′ untranslated region (UTR) of SOCS1. The inhibition of IFN-λ elicited ISGs expression by SOCS1 was specifically rescued by overexpression of miR-30c-5p. Collectively, our findings identify a new strategy by PEDV to escape IFN-λ-mediated antiviral immune responses by engaging the SOCS1/miR-30c axis, thus improving our understanding of its pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/32574254/ doi: 10.3389/fmicb.2020.01180 id: cord-333423-jhm7u8ka author: Wang, Dang title: Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Type I Interferon Signaling by Targeting IRF9 date: 2019-05-15 words: 7204.0 sentences: 390.0 pages: flesch: 48.0 cache: ./cache/cord-333423-jhm7u8ka.txt txt: ./txt/cord-333423-jhm7u8ka.txt summary: Furthermore, the nsp11-IRF9 interaction impaired the formation and nuclear translocation of the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) in both nsp11-overexpressed and PRRSV-infected cells. Taking the results together, our study demonstrated that PRRSV nsp11 antagonizes type I IFN signaling by targeting IRF9 via a NendoU activity-independent mechanism, and this report describes a novel strategy evolved by PRRSV to counteract host innate antiviral responses, revealing a potential new function for PRRSV nsp11 in type I IFN signaling. The type I IFN-activated ISGF3 transcription complex containing tyrosine-phosphorylated STAT1 and STAT2 associated with IRF9 is rapidly translocated to the nucleus FIG 3 PRRSV nsp11 inhibits ISGF3-induced ISRE promoter activity. This provided further support for the notion that the ability of PRRSV nsp11 to block type I IFN signaling is independent of its endoribonuclease activity and cell cytotoxicity, because these three mutants had similar effects with respect to inhibiting the formation and nuclear translocation of ISGF3 compared with WT nsp11. abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus from the Nidovirales order that causes reproductive failure and respiratory disease in pigs and poses a constant threat to the global pig industry. The PRRSV-encoded nonstructural protein 11 (nsp11) is a nidovirus-specific endoribonuclease (NendoU) that is conserved throughout the Arteriviridae and Coronaviridae families. Previously, our research and that of others demonstrated that PRRSV nsp11 inhibits type I interferon (IFN) production through NendoU activity-dependent mechanisms. Here, we found that PRRSV nsp11 also inhibited IFN-stimulated response element (ISRE) promoter activity and subsequent transcription of IFN-stimulated genes (ISGs). Detailed analysis showed that nsp11 targeted interferon regulatory factor 9 (IRF9), but not transducer and activator of transcription 1 (STAT1) or STAT2, key molecules in the type I IFN signaling pathway. Furthermore, the nsp11-IRF9 interaction impaired the formation and nuclear translocation of the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) in both nsp11-overexpressed and PRRSV-infected cells. Importantly, nsp11 mutations (H129A, H144A, and K173A) that ablate NendoU activity or its cell cytotoxicity also interacted with IRF9 and retained the ability to block IFN signaling, indicating that the nsp11-IRF9 interaction is independent of NendoU activity or cell cytotoxicity of nsp11. Taking the results together, our study demonstrated that PRRSV nsp11 antagonizes type I IFN signaling by targeting IRF9 via a NendoU activity-independent mechanism, and this report describes a novel strategy evolved by PRRSV to counteract host innate antiviral responses, revealing a potential new function for PRRSV nsp11 in type I IFN signaling. IMPORTANCE The nidovirus-specific endoribonuclease (NendoU) encoded by PRRSV nonstructural protein 11 (nsp11) is a unique NendoU of nidoviruses that infect vertebrates; thus, it is an attractive target for the development of antinidovirus drugs. Previous studies have revealed that the NendoU of nidoviruses, including porcine reproductive and respiratory syndrome virus (PRRSV) and human coronavirus 229E (HCoV-229E), acts as a type I interferon (IFN) antagonist. Here, for the first time, we demonstrated that overexpression of PRRSV nsp11 also inhibits IFN signaling by targeting the C-terminal interferon regulatory factor (IRF) association domain of IRF9. This interaction impaired the ability of IRF9 to form the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) and to act as a signaling protein of IFN signaling. Collectively, our data identify IRF9 as a natural target of PRRSV NendoU and reveal a novel mechanism evolved by an arterivirus to counteract innate immune signaling. url: https://jvi.asm.org/content/jvi/93/15/e00623-19.full.pdf doi: 10.1128/jvi.00623-19 id: cord-287874-wl0wlxh6 author: Wang, Ling title: Quadruple therapy for asymptomatic COVID-19 infection patients date: 2020-05-03 words: 5530.0 sentences: 267.0 pages: flesch: 45.0 cache: ./cache/cord-287874-wl0wlxh6.txt txt: ./txt/cord-287874-wl0wlxh6.txt summary: From 31 January 2020 to 10 February 2020, the patient was given quadruple therapy, including lopinavir/ritonavir tablets (400/100 mg every 12 h), arbidol tablets (0.2 g every 8 h), Lianhuaqingwen granules (a Chinese patent medicine, 6 g every 8 h) orally, and recombinant human interferon-α2b injection via aerosol (6.0 × 10 6 IU with 2 ml of sterilized water for injection every 12 h). • Quadruple therapy, which is lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol, is a common regimen for patients with COVID-19 in China. From 31 January 2020 to 10 February 2020, the patient was treated with four drugs, which are oral administration of lopinavir/ritonavir tablets (400/100 mg every 12 h), arbidol tablets (0.2 g every 8 h), and Lianhuaqingwen granules (a Chinese patent medicine, 6 g every 8 h) and atomization inhalation of recombinant human interferon-α2b injection (6.0 × 10 6 IU with 2 ml of sterilized water for injection every 12 h). abstract: Introduction: The novel coronavirus (COVID-19) is currently in epidemic stage. After large-scale interpersonal infection, asymptomatic patients appear. Whether asymptomatic patients are contagious or not and whether they need medication are the arguments among clinical experts. Areas covered: This paper reports a special asymptomatic couple with COVID-19, of which the male patient is an intercity bus driver but has not induced confirmed infection of his 188 passengers. The patients were treated with four combinations of lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol. Their clinical characteristics and medication were summarized and analyzed. Expert opinion: The two asymptomatic patients far away from Wuhan did not seem to be highly contagious. They improved obviously, after treatment with the quadruple therapy, but the effective drug is still unknown. It should be noted that lopinavir/ritonavir tablets have many drug interactions and are the most likely drugs to cause hyperlipidemia and hyperglycemia in these two patients. IFN-α2b is more effective in the early stage of virus infection. Arbidol instruction dose may not be sufficient to inhibit the novel coronavirus in vivo. The evidence-based medicine of Lianhuaqingwen granules for treating various viral infections is just based on Chinese patients. url: https://www.ncbi.nlm.nih.gov/pubmed/32362193/ doi: 10.1080/14787210.2020.1758066 id: cord-280005-i9fp5rys author: Wang, Mengmei title: Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide -- a Single-Center, Randomized, Controlled Clinical Trial date: 2020-09-21 words: 3185.0 sentences: 172.0 pages: flesch: 49.0 cache: ./cache/cord-280005-i9fp5rys.txt txt: ./txt/cord-280005-i9fp5rys.txt summary: title: Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide -a Single-Center, Randomized, Controlled Clinical Trial CONCLUSIONS: In COVID-19 patients with prolonged PCR positivity, no benefit in terms of the duration of viral shedding was observed with the combined treatment of leflunomide and IFN α-2a beyond IFN α-2a alone. Based on that background, we conducted a prospective randomized, controlled, open-label trial, to evaluate the efficacy and safety of oral leflunomide to treat hospitalized COVID-19 patients with prolonged post-symptomatic viral shedding. Fifty eligible patients were randomly assigned to a combination treatment group that received leflunomide (50 mg, q12h, three consecutive times, orally; then 20 mg, once a day for 8 days; a total course of 10 days) plus nebulized IFN -2a (3 million IU each time, adding 2 ml of sterilized water, atomization inhalation twice daily for 10 days), or to a control group that received nebulized IFN -2a This was an open-label, prospective randomized, controlled trial, which was conducted at East Campus, Renmin Hospital of Wuhan University. abstract: OBJECTIVE: To evaluate the efficacy and safety of leflunomide, an approved dihydroorotate dehydrogenase inhibitor, to treat COVID-19 patients with prolonged post-symptomatic viral shedding. METHODS: We conducted a prospective, randomized, controlled, open-label trial involving hospitalized adult COVID-19 patients with prolonged PCR positivity. Patients were randomly assigned to receive either leflunomide (50 mg, q12h, three consecutive times, orally; then 20 mg, once daily for 8 days), in addition to nebulized interferon alpha 2a (IFN α-2a, 3 million IU each time, twice daily for 10 days), or nebulized IFN α-2a alone for 10 days. The primary end point was the duration of viral shedding. RESULTS: A total of 50 COVID-19 patients with prolonged PCR positivity were randomized into 2 groups; 26 were assigned to the leflunomide group, and 24 were assigned to the interferon alone group. Treatment with leflunomide was not associated with a difference from the interferon alone group in the duration of viral shedding (hazard ratio for negative RT-PCR, 0.70; 95% confidence interval, 0.391-1.256; P=0.186). In addition, the patients given leflunomide did not have a substantially shorter length of hospital stay than patients treated with interferon alone, with median (IQRs) durations of 29.0 (19.3-47.3) days and 33.0 (29.3-42.8) days, respectively, P=0.170. Two leflunomide recipients were unable to complete the full 10-day course of administration due to adverse events. CONCLUSIONS: In COVID-19 patients with prolonged PCR positivity, no benefit in terms of the duration of viral shedding was observed with the combined treatment of leflunomide and IFN α-2a beyond IFN α-2a alone. url: https://www.ncbi.nlm.nih.gov/pubmed/32955081/ doi: 10.1093/cid/ciaa1417 id: cord-354730-hfau2odb author: Wang, Rong title: Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus date: 2014-07-03 words: 4923.0 sentences: 312.0 pages: flesch: 45.0 cache: ./cache/cord-354730-hfau2odb.txt txt: ./txt/cord-354730-hfau2odb.txt summary: PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. This review summarizes the recent advances in the research of PRRSV interference with IFN-mediated innate immunity, the viral proteins involved, and their molecular mechanisms, as well as diverse effects by different strains and in different cell types. These transcription activation factors translocate into the nucleus and result in induction of type I IFNs and expression of inflammatory cytokines, which not only lead to an antiviral state of the neighboring uninfected cells, but also serve as key regulators to evoke adaptive immune response. Porcine reproductive and respiratory syndrome virus nonstructural protein 1 modulates host innate immune response by antagonizing IRF3 activation Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear translocation abstract: Interferons (IFNs) are important components in innate immunity involved in the first line of defense to protect host against viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) leads to severe economic losses for swine industry since being first identified in early 1990s. PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. PRRSV encodes several proteins that act as antagonists for the IFN signaling. In this review, we summarized the various strategies used by PRRSV to antagonize IFN production and thwart IFN-activated antiviral signaling, as well as the variable interference with IFN-mediated immune response by different PRRSV strains. Thorough understanding of the interaction between PRRSV and host innate immune response will facilitate elucidation of PRRSV pathogenesis and development of a better strategy to control PRRS. url: https://www.ncbi.nlm.nih.gov/pubmed/25101271/ doi: 10.1155/2014/315470 id: cord-009813-o8ai730r author: Wang, Wei title: Major vault protein plays important roles in viral infection date: 2019-11-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viral replication and related protein expression inside the host cells, and host antiviral immune responses can lead to the occurrence of diverse diseases. With the outbreak of viral infection, a large number of newly diagnosed and died patients infected with various viruses are still reported every year. Viral infection has already been one of the major global public health issues and lead to huge economic and social burdens. Studying of viral pathogenesis is a very important way to find methods for prevention, diagnosis, and cure of viral infection; more evidence has confirmed that major vault protein (MVP) is closely associated with viral infection and pathogenesis, and this review is intended to provide a broad relationship between viruses and MVP to stimulate the interest of related researchers. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165711/ doi: 10.1002/iub.2200 id: cord-270380-1me7ugkg author: Wang, Xiaona title: Cloning, Prokaryotic Soluble Expression, and Analysis of Antiviral Activity of Two Novel Feline IFN-ω Proteins date: 2020-03-19 words: 5963.0 sentences: 300.0 pages: flesch: 46.0 cache: ./cache/cord-270380-1me7ugkg.txt txt: ./txt/cord-270380-1me7ugkg.txt summary: Both proteins exhibited effective anti-vesicular stomatitis virus (VSV) activity in Vero, F81 (feline kidney cell), Madin–Darby bovine kidney (MDBK), Madin–Darby canine kidney (MDCK), and porcine kidney (PK-15) cells, showing broader cross-species antiviral activity than the INTERCAT IFN antiviral drug. Furthermore, the recombinant feIFN-ωa and feIFN-ωb proteins demonstrated antiviral activity against VSV, feline coronavirus (FCoV), canine parvovirus (CPV), bovine viral diarrhea virus (BVDV), and porcine epidemic diarrhea virus (PEDV), indicating better broad-spectrum antiviral activity than the INTERCAT IFN. As shown in Figure 6 , the purified recombinant feIFN-ωa and feIFN-ωb proteins showed antiviral activity in both homologous animal cells (F81 cells) and heterologous animal cells (Vero, MDCK, MDBK, and PK-15 cells) in vitro. Our data showed that purified recombinant feIFN-ωa and feIFN-ωb had broad-spectrum antiviral activity in homologous and heterologous animal cells, suggesting they are candidates for the development of effective therapeutic agents to be used against viral infections in pet cats. abstract: Cats are becoming more popular as household companions and pets, forming close relationships with humans. Although feline viral diseases can pose serious health hazards to pet cats, commercialized preventative vaccines are lacking. Interferons (IFNs), especially type I IFNs (IFN-α, IFN-β, and interferon omega (IFN-ω)), have been explored as effective therapeutic drugs against viral diseases in cats. Nevertheless, there is limited knowledge regarding feline IFN-ω (feIFN-ω), compared to IFN-α and IFN-β. In this study, we cloned the genes encoding feIFN-ωa and feIFN-ωb from cat spleen lymphocytes. Homology and phylogenetic tree analysis revealed that these two genes belonged to new subtypes of feIFN-ω. The recombinant feIFN-ωa and feIFN-ωb proteins were expressed in their soluble forms in Escherichia coli, followed by purification. Both proteins exhibited effective anti-vesicular stomatitis virus (VSV) activity in Vero, F81 (feline kidney cell), Madin–Darby bovine kidney (MDBK), Madin–Darby canine kidney (MDCK), and porcine kidney (PK-15) cells, showing broader cross-species antiviral activity than the INTERCAT IFN antiviral drug. Furthermore, the recombinant feIFN-ωa and feIFN-ωb proteins demonstrated antiviral activity against VSV, feline coronavirus (FCoV), canine parvovirus (CPV), bovine viral diarrhea virus (BVDV), and porcine epidemic diarrhea virus (PEDV), indicating better broad-spectrum antiviral activity than the INTERCAT IFN. The two novel feIFN-ω proteins (feIFN-ωa and feIFN-ωb) described in this study show promising potential to serve as effective therapeutic agents for treating viral infections in pet cats. url: https://doi.org/10.3390/v12030335 doi: 10.3390/v12030335 id: cord-252671-uf96jgig author: Wang, Yi title: The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism date: 2016-02-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Most of the intracellular pattern recognition receptors (PRRs) reside in either the endolysosome or the cytoplasm to sense pathogen-derived RNAs, DNAs, or synthetic analogs of double-stranded RNA (dsRNA), such as poly(I:C). However, it remains elusive whether or not a pathogen-derived protein can function as a cytosolic pathogen-associated molecular pattern (PAMP). In this study, we demonstrate that delivering the membrane gene of severe acute respiratory syndrome coronavirus (SARS-CoV) into HEK293T, HEK293ET, and immobilized murine bone marrow-derived macrophage (J2-Mφ) cells significantly upregulates beta interferon (IFN-β) production. Both NF-κB and TBK1-IRF3 signaling cascades are activated by M gene products. M protein rather than M mRNA is responsible for M-mediated IFN-β induction that is preferentially associated with the activation of the Toll-like receptor (TLR) adaptor proteins MyD88, TIRAP, and TICAM2 but not the RIG-I signaling cascade. Blocking the secretion of M protein by brefeldin A (BFA) failed to reverse the M-mediated IFN-β induction. The antagonist of both TLR2 and TLR4 did not impede M-mediated IFN-β induction, indicating that the driving force for the activation of IFN-β production was generated from inside the cells. Inhibition of TRAF3 expression by specific small interfering RNA (siRNA) did not prevent M-mediated IFN-β induction. SARS-CoV pseudovirus could induce IFN-β production in an M rather than M(V68A) dependent manner, since the valine-to-alanine alteration at residue 68 in M protein markedly inhibited IFN-β production. Overall, our study indicates for the first time that a pathogen-derived protein is able to function as a cytosolic PAMP to stimulate type I interferon production by activating a noncanonical TLR signaling cascade in a TRAF3-independent manner. url: https://www.ncbi.nlm.nih.gov/pubmed/26861016/ doi: 10.1128/mbio.01872-15 id: cord-266914-3eatplc2 author: Wang, Yongjin title: Nsp1 proteins of group I and SARS coronaviruses share structural and functional similarities date: 2010-06-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The nsp1 protein of the highly pathogenic SARS coronavirus suppresses host protein synthesis, including genes involved in the innate immune system. A bioinformatic analysis revealed that the nsp1 proteins of group I and SARS coronaviruses have similar structures. Nsp1 proteins of group I coronaviruses interacted with host ribosomal 40S subunit and did not inhibit IRF-3 activation. However, synthesis of host immune and non-immune proteins was inhibited by nsp1 proteins at both transcriptional and translational levels, similar to SARS coronavirus nsp1. These results indicate that different coronaviruses might employ the same nsp1 mechanism to antagonize host innate immunity and cell proliferation. However, nsp1 may not be the key determinant of viral pathogenicity, or the factor used by the SARS coronavirus to evade host innate immunity. url: https://www.sciencedirect.com/science/article/pii/S1567134810001371 doi: 10.1016/j.meegid.2010.05.014 id: cord-273050-reez33md author: Wang, Zhenling title: Type I IFN deficiency: an immunological characteristic of severe COVID-19 patients date: 2020-09-14 words: 1337.0 sentences: 85.0 pages: flesch: 46.0 cache: ./cache/cord-273050-reez33md.txt txt: ./txt/cord-273050-reez33md.txt summary: reported that type I interferon (IFN) deficiency, could be a hallmark of severe coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compared with patients that had mild-to-moderate infection, the ISG score (based on the mean expression value of six ISGs defining a type I IFN signature) was significantly reduced in critical patients. By correlated analysis of viral loading with IFN-α production either on protein or on gene level, the authors suggest that the most severe cases of COVID-19 are featured by impaired IFN-α production. To further explore the transcription factors that may cause the excessive inflammatory response of COVID-19, the authors observed that upregulated genes in severe or critical patients mainly belonged to the NF-κB pathway by a kinetic analysis. Impaired type I IFN response featured immunological characteristics of severe COVID-19 patients, accompanied by lymphocytopenia, hypercytokinaemia, and high blood viral load. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients abstract: nan url: https://doi.org/10.1038/s41392-020-00306-4 doi: 10.1038/s41392-020-00306-4 id: cord-272237-gnno6elo author: Wang, Ziran title: A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids date: 2020-07-31 words: 4472.0 sentences: 241.0 pages: flesch: 53.0 cache: ./cache/cord-272237-gnno6elo.txt txt: ./txt/cord-272237-gnno6elo.txt summary: A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). Moreover, Tween 80 is used to modify the graphene surface to effectively suppress nonspecific adsorption, thus enabling the biosensor to detect cytokines (TNF-α and IFN-γ, significant inflammatory cytokines, were used as representatives) in artificial tears (used as a biofluid representative). abstract: A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, a nonionic surfactant is employed to minimize the nonspecific adsorption of the biosensor, hence enabling cytokine detection (TNF-α and IFN-γ, significant inflammatory cytokines, are used as representatives) in artificial tears (used as a biofluid representative). The experimental results demonstrate that the biosensor very consistently and sensitively detects TNF-α and IFN-γ, with limits of detection down to 2.75 and 2.89 pM, respectively. The biosensor, which undergoes large deformations, can thus potentially provide a consistent and sensitive detection of cytokines in the human body. url: https://doi.org/10.3390/nano10081503 doi: 10.3390/nano10081503 id: cord-354000-jxqskt4k author: Warren, Cody J. title: The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date: 2014-05-14 words: 4420.0 sentences: 265.0 pages: flesch: 47.0 cache: ./cache/cord-354000-jxqskt4k.txt txt: ./txt/cord-354000-jxqskt4k.txt summary: Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. IFITM protein expression induced by type I IFN inhibits infection of many RNA viruses [22] [23] [24] [25] [26] [27] [28] [29] [30] . Therefore, we analyzed induction of IFITM1, 2 and 3 expression by IFN-b treatment in human keratinocytes, the natural host cells for HPV. To determine the effect of IFITMs on HPV16 entry, HeLa cells stably expressing c-Myc-tagged IFITM1, 2 or 3 or with vector alone ( Fig. 2A-B) were infected with HPV16-LucF. Using various epithelial cell lines and primary keratinocytes expressing IFITMs, we show that HPV infection is surprisingly enhanced by IFITM1 and IFITM3 overexpression (Fig. 2) . Taken together, our results suggest that HPV and other DNA viruses may have evolved to avoid IFITM1, 2 and 3 restriction during entry into host cells. abstract: Type I interferons (IFN-α and β) induce dynamic host defense mechanisms to inhibit viral infections. It has been recently recognized that the interferon-inducible transmembrane proteins (IFITM) 1, 2 and 3 can block entry of a broad spectrum of RNA viruses. However, no study to date has focused on the role of IFITM proteins in DNA virus restriction. Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. However, IFITM1, 2 and 3 overexpression did not inhibit HPV16 infection; rather, IFITM1 and IFITM3 modestly enhanced HPV16 infection in various cell types including primary keratinocytes. Moreover, IFITM1, 2 and 3 did not inhibit infection by two other DNA viruses, human cytomegalovirus (HCMV) and adenovirus type 5 (Ad5). Taken together, we reveal that the entry of several DNA viruses, including HPV, HCMV, and Ad5 is not affected by IFITM1, 2 and 3 expression. These results imply that HPV, and other DNA viruses, may bypass IFITM restriction during intracellular trafficking. url: https://doi.org/10.1371/journal.pone.0096579 doi: 10.1371/journal.pone.0096579 id: cord-328947-3l9ydspz author: Webb, L. G. title: Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date: 2020-10-15 words: 9857.0 sentences: 544.0 pages: flesch: 51.0 cache: ./cache/cord-328947-3l9ydspz.txt txt: ./txt/cord-328947-3l9ydspz.txt summary: CHIKV is no exception, the type-I interferon (IFN) response has been demonstrated to be key in controlling CHIKV infection [21] [22] [23] [24] [25] [26] and primary sensing of the virus is via the pattern recognition receptor (PRR) retinoic acid-inducible gene I (RIG-I)-mitochondrial antiviral signaling protein (MAVS) axis [24, 26] . The lack of cGAS degradation seen in the exogenous expression system when compared to the infected cells shows that although there is a clear interaction of cGAS with nsP4, the degradation of cGAS observed is not mediated by the non-structural proteins of CHIKV, but must require other viral or host factors. Chikungunya virus inhibits DNA sensing by degrading cGAS both mock and infected cells by 4 hpi suggesting that the stress produced during the process of infection (mock or CHIKV) in HFF-1s stimulates increased translation at early timepoints ( Fig 4D, lanes 2 and 5) . abstract: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which in rare cases cause long term debilitating arthritis and arthralgia. Significant progress has been made in understanding the roles of canonical RNA sensing pathways in the host recognition of CHIKV; however, less is known regarding antagonism of CHIKV by cytosolic DNA sensing pathways like that of cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). With the use of cGAS or STING null cells we demonstrate that the pathway restricts CHIKV replication in fibroblasts and immune cells. We show that DNA accumulates in the cytoplasm of infected cells and that CHIKV blocks DNA dependent IFN-β transcription. This antagonism of DNA sensing is via an early autophagy-mediated degradation of cGAS and expression of the CHIKV capsid protein is sufficient to induce cGAS degradation. Furthermore, we identify an interaction of CHIKV nsP1 with STING and map the interaction to 23 residues in the cytosolic loop of the adaptor protein. This interaction stabilizes the viral protein and increases the level of palmitoylated nsP1 in cells. Together, this work supports previous publications highlighting the relevance of the cGAS-STING pathway in the early detection of (+)ssRNA viruses and provides direct evidence that CHIKV interacts with and antagonizes cGAS-STING signaling. url: https://doi.org/10.1371/journal.ppat.1008999 doi: 10.1371/journal.ppat.1008999 id: cord-280130-ewqe9edq author: Weber, Friedemann title: Viral suppression of the interferon system date: 2007-01-27 words: 4298.0 sentences: 224.0 pages: flesch: 39.0 cache: ./cache/cord-280130-ewqe9edq.txt txt: ./txt/cord-280130-ewqe9edq.txt summary: In most nucleated body cells, viral infections activate transcription of the ''''classic'''' IFN-b gene [1] by a signaling chain which is initiated by the RNA sensors RIG-I and MDA-5, which in turn act trough the adaptor IPS-1 and the kinases TBK-1 and IKK-3 to activate the transcription factor IRF-3 (see reviews by P. Many RNA and DNA viruses therefore express proteins which bind this key molecule to avoid both IFN induction and activation of dsRNA-dependent antiviral enzymes [7, 8] . Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling Double-stranded RNA binding of influenza B virus nonstructural NS1 protein inhibits protein kinase R but is not essential to antagonize production of alpha/beta interferon abstract: Type I interferons (IFN-α/β) were originally discovered by their strong and direct antiviral activity [A. Isaacs, J. Lindenmann, Virus interference. I. The interferon, Proc. R. Soc. Lond. B Biol. Sci. 147 (1957) 258–267]. (see review by J. Lindenmann on p. 719, in this issue). Nevertheless, only very recently it was entirely realized that viruses would not succeed without efficient tools to undermine this potent host defense system. Current investigations are revealing an astonishing variety of viral IFN antagonistic strategies targeting virtually all parts of the IFN system, often in a highly specific manner. Viruses were found to interfere with induction of IFN synthesis, IFN-induced signaling events, the antiviral effector proteins, or simply shut off the host cell macromolecule synthesis machinery to avoid booting of the antiviral host defense. Here, we will describe a few well-characterized examples to illustrate the sophisticated and often multi-layered anti-IFN mechanisms employed by viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/17336442/ doi: 10.1016/j.biochi.2007.01.005 id: cord-330176-1ugzkf22 author: Weeratunga, Prasanna title: RETRACTED ARTICLE: Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components date: 2016-01-05 words: 7948.0 sentences: 396.0 pages: flesch: 53.0 cache: ./cache/cord-330176-1ugzkf22.txt txt: ./txt/cord-330176-1ugzkf22.txt summary: In vitro, an effective dose of Angelica tenuissima Nakai markedly inhibited the replication of Influenza A virus (PR8), Vesicular stomatitis virus (VSV), Herpes simplex virus (HSV), Coxsackie virus, and Enterovirus (EV-71) on epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. To investigate the antiviral effects in immune cells, we first assessed the replication of divergent GFP-expressing viruses that were treated or untreated with cytotoxic-free (data not shown) Angelica tenuissima Nakai in RAW264.7 cells. These results suggest that the aqueous extract of Angelica tenuissima Nakai can induce the secretion of IFNs and pro-inflammatory cytokines, which can stimulate the cellular antiviral state for inhibition of viral replication. The aqueous extract of Angelica tenuissima Nakai inhibit the diverse viral infection through the induction of Type I IFN signaling and pro-inflammatory cytokines, leading to an antiviral state in epithelial and immune cells. abstract: Angelica tenuissima Nakai is a widely used commodity in traditional medicine. Nevertheless, no study has been conducted on the antiviral and immune-modulatory properties of an aqueous extract of Angelica tenuissima Nakai. In the present study, we evaluated the antiviral activities and the mechanism of action of an aqueous extract of Angelica tenuissima Nakai both in vitro and in vivo. In vitro, an effective dose of Angelica tenuissima Nakai markedly inhibited the replication of Influenza A virus (PR8), Vesicular stomatitis virus (VSV), Herpes simplex virus (HSV), Coxsackie virus, and Enterovirus (EV-71) on epithelial (HEK293T/HeLa) and immune (RAW264.7) cells. Such inhibition can be described by the induction of the antiviral state in cells by antiviral, IFNrelated gene induction and secretion of IFNs and pro-inflammatory cytokines. In vivo, Angelica tenuissima Nakai treated BALB/c mice displayed higher survivability and lower lung viral titers when challenged with lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3, and H9N2). We also found that Angelica tenuissima Nakai can induce the secretion of IL-6, IFN-λ, and local IgA in bronchoalveolar lavage fluid (BALF) of Angelica tenuissima Nakai treated mice, which correlating with the observed prophylactic effects. In HPLC analysis, we found the presence of several compounds in the aqueous fraction and among them; we evaluated antiviral properties of ferulic acid. Therefore, an extract of Angelica tenuissima Nakai and its components, including ferulic acid, play roles as immunomodulators and may be potential candidates for novel anti-viral/anti-influenza agents. url: https://www.ncbi.nlm.nih.gov/pubmed/26727903/ doi: 10.1007/s12275-016-5555-4 id: cord-023389-ilrp8vb7 author: Wefer, J. title: Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: DNA vaccine coding for the encephalitogenic peptide MOG(91‐108) protects LEW.1AV1 from subsequent development of experimental autoimmune encephalomyelitis (EAE). Protection is associated with a type 1 immune response and is dependent on the presence of CpG DNA motifs. The mechanisms underlying the observed reduction of EAE development in protected rats have not been fully clarified. We investigated immunological characteristics of lymphocytes after DNA vaccinaton and subsequent EAE induction. We confirm that protection was not associated with suppression of T1 cells, as transcription of the novel molecule rat T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule (TIM‐3), reported to be exclusively expressed on differentiated T1 cells, was not altered by DNA vaccination. We did not note any clonal deletion upon tolerization, but detected an antigen‐specific lymphocyte population upregulating IFNγ upon recall stimulation 3 weeks after protective DNA vaccination. In protected rats, we observed (1) no alterations in antigen‐specific Th2 or Th3 responses, (2) reduced MHC II expression on splenocytes early after EAE induction, (3) antigen‐specific upregulation of IFNβ upon recall stimulation and (4) reduced IL‐12Rβ2 on lymphocytes. We thus demonstrate an association of the protective effect of DNA vaccination with expression of IFNβ. We are currently investigating the cellular mechanisms behind this IFNβ‐mediated protection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169512/ doi: 10.1111/j.0300-9475.2004.01423j.x id: cord-007646-yh8zi1ee author: Weiss, R.C. title: Effect of recombinant human interferon-alpha in vitro and in vivo on mitogen-induced lymphocyte blastogenesis in cats() date: 2002-11-12 words: 3828.0 sentences: 199.0 pages: flesch: 48.0 cache: ./cache/cord-007646-yh8zi1ee.txt txt: ./txt/cord-007646-yh8zi1ee.txt summary: The effect of recombinant human interferon-alpha (rHuIFN-α) in vitro and in vivo on mitogen-induced lymphocyte blastogenesis was evaluated in specific-pathogen-free cats. Pre-incubation of isolated feline peripheral blood lymphocytes (PBL) in vitro with either 104 or 103 International Units (U) of rHuIFN-o~ for 24 h significantly suppressed (P < 0.001 and 0.01, respectively) blastogenic responses to the phytomitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Pre-incubation of isolated feline peripheral blood lymphocytes (PBL) in vitro with either 104 or 103 International Units (U) of rHuIFN-o~ for 24 h significantly suppressed (P < 0.001 and 0.01, respectively) blastogenic responses to the phytomitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Although the suppressive mechanism (s) associated with rHuIFN-c~ on DNA synthesis and lymphocyte blastogenesis were not investigated in our study, it is possible that high doses of IFN in vitro enhanced lectin-binding on lymphocytes and stimulated suppressor cell activities. abstract: The effect of recombinant human interferon-alpha (rHuIFN-α) in vitro and in vivo on mitogen-induced lymphocyte blastogenesis was evaluated in specific-pathogen-free cats. Pre-incubation of isolated feline peripheral blood lymphocytes (PBL) in vitro with either 10(4) or 10(3) International Units (U) of rHuIFN-α for 24 h significantly suppressed (P<0.001 and 0.01, respectively) blastogenic responses to the phytomitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Lower doses of IFN (range, 10–10(−3) U/ml) neither suppressed nor enhanced mitogenesis. In the absence of phytomitogens, incubation of PBL with 10(4)–10(2) U (P<0.001) or 10 U (P<0.05) of rHuIFN-α/ml resulted in a significant decrease in incorporation of [methyl-(3)H] thymidine into newly synthesized cellular DNA. Cultures of PBL exposed continuously for 4 days to rHuIFN-α doses of 10(4) U/ml or less did not demonstrate specific reductions in cell viability, indicating that the observed antiproliferative actions of IFN apparently were independent of any direct cytotoxic effects. To investigate the dose-response effects of rHuIFN-α in vivo on lymphocyte blastogenesis, individual groups of cats were evaluated on 3 consecutive days before and then 24 h after each cat was inoculated intramuscularly with either a high dose (10(6) U/kg), moderate dose (10(4) U/kg), or a relatively low dose (10(2) U/kg) of rHuIFN-α. Cats inoculated with 10(6) U ofrHuIFN-α/kg had significantly reduced (P=0.037) blastogenic responses to Con a at 24 h postinoculation compared to preinoculation values; mean PWM responses were also decreased, but this effect was not statistically significant. In contrast, inoculation of cats with either 10(4) or 10(2) U of rHuIFN-α/kg significantly enhanced (P=0.05 or 0.008, respectively) Con A-induced blastogenesis and had no discernible effect on PWM responses. These findings suggest that very high doses of rHuIFN-α given parenterally may be associated with suppression of certain T-cell responses in cats; conversely, much lower doses may be immunoenhancing. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119795/ doi: 10.1016/0165-2427(90)90017-m id: cord-258691-cd83w9o6 author: Whitman, Lucia title: IFN-γ-mediated suppression of coronavirus replication in glial-committed progenitor cells date: 2009-02-01 words: 4938.0 sentences: 257.0 pages: flesch: 40.0 cache: ./cache/cord-258691-cd83w9o6.txt txt: ./txt/cord-258691-cd83w9o6.txt summary: IFN-γ-mediated control of JHMV replication is dampened in glial cultures derived from the neural progenitor cells of type I receptor knock-out mice. These data indicate that JHMV is capable of infecting glial cells generated from neural progenitor cells and that IFN-γ-mediated control of viral replication is dependent, in part, on type I IFN secretion. In the present study, we demonstrate that primary cultures of glia derived from neural progenitor cells are susceptible to JHMV infection and support viral replication. Therefore, these findings provide, to our knowledge, the first demonstration that glia-committed cells derived from neural precursors are susceptible to JHMV infection as well as identify a potential mechanism responsible for controlling viral replication. These findings indicate that differentiated cells derived from neural progenitors are susceptible to JHMV infection and are capable of supporting replicating virus which results in extensive cytopathology. abstract: The neurotropic JHM strain of mouse hepatitis virus (JHMV) replicates primarily within glial cells following intracranial inoculation of susceptible mice, with relative sparing of neurons. This study demonstrates that glial cells derived from neural progenitor cells are susceptible to JHMV infection and that treatment of infected cells with IFN-γ inhibits viral replication in a dose-dependent manner. Although type I IFN production is muted in JHMV-infected glial cultures, IFN-β is produced following IFN-γ-treatment of JHMV-infected cells. Also, direct treatment of infected glial cultures with recombinant mouse IFN-α or IFN-β inhibits viral replication. IFN-γ-mediated control of JHMV replication is dampened in glial cultures derived from the neural progenitor cells of type I receptor knock-out mice. These data indicate that JHMV is capable of infecting glial cells generated from neural progenitor cells and that IFN-γ-mediated control of viral replication is dependent, in part, on type I IFN secretion. url: https://api.elsevier.com/content/article/pii/S0042682208006971 doi: 10.1016/j.virol.2008.10.036 id: cord-021872-rhi7hi9m author: Wilkes, Rebecca P. title: Update on Antiviral Therapies date: 2015-12-04 words: 9933.0 sentences: 524.0 pages: flesch: 47.0 cache: ./cache/cord-021872-rhi7hi9m.txt txt: ./txt/cord-021872-rhi7hi9m.txt summary: Topical antiviral therapy has been mainly used for herpetic ocular disease, but studies have evaluated a systemic antiviral compound (famciclovir) for treatment of multiple clinical syndromes associated with FHV-1 infections. 7 A related drug, (R)-9-(2-phosphonylmethoxypropyl)-2,6diaminopurine (PMPDAP), has been shown previously to be a potent inhibitor of FIV replication in cell culture and has reduced the viral load in three of four cats experimentally infected with FIV when treated at 20 mg/kg SC three times per week for 6 weeks. 1 A prodrug of acyclovir, valacyclovir, was developed for increased bioavailability in humans, but use for FHV-1 treatment in experimentally infected cats induced fatal renal and hepatic necrosis and bone marrow suppression, and did not reduce viral shedding or clinical disease severity. 20 Even though this study did not mimic how cats with natural infection would be treated, results from a clinical case study suggested this drug is likely effective for treatment of clinical cases, though it was not blinded and placebo controlled. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152142/ doi: 10.1016/b978-0-323-22652-3.00007-4 id: cord-282947-3hgku2e4 author: Wong, Hui Hui title: Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3 date: 2017-12-30 words: 8714.0 sentences: 423.0 pages: flesch: 46.0 cache: ./cache/cord-282947-3hgku2e4.txt txt: ./txt/cord-282947-3hgku2e4.txt summary: title: Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3 Through the construction of recombinant IBV expressing proteins 8a, 8b and 8ab encoded by SARS-CoV ORF8, we demonstrate that expression of 8b and 8ab enables the corresponding recombinant viruses to partially overcome the inhibitory actions of IFN activation to achieve higher replication efficiencies in cells. Compared to wild type and rIBV8a/b, however, rIBV8b and rIBV8ab were observed to replicate significantly better and express higher levels of N protein in cells stimulated by poly (I:C) (Fig. 2a) . In view of the central role of IRF3 in regulating IFN activation during virus infection, 8b and 8ab with Flag epitope-tagged to their Ntermini were co-expressed with Myc-tagged IRF3 (Fig. 3a) in Cos-7 cells using the vaccinia/T7 expression system (Anderson et al., 1996; Lim and Liu, 2001) for co-immunoprecipitation assays to determine if there is any physical interaction between the proteins. abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) is an inefficient inducer of interferon (IFN) response. It expresses various proteins that effectively circumvent IFN production at different levels via distinct mechanisms. Through the construction of recombinant IBV expressing proteins 8a, 8b and 8ab encoded by SARS-CoV ORF8, we demonstrate that expression of 8b and 8ab enables the corresponding recombinant viruses to partially overcome the inhibitory actions of IFN activation to achieve higher replication efficiencies in cells. We also found that proteins 8b and 8ab could physically interact with IRF3. Overexpression of 8b and 8ab resulted in the reduction of poly (I:C)-induced IRF3 dimerization and inhibition of the IFN-β signaling pathway. This counteracting effect was partially mediated by protein 8b/8ab-induced degradation of IRF3 in a ubiquitin-proteasome-dependent manner. Taken together, we propose that SARS-CoV may exploit the unique functions of proteins 8b and 8ab as novel mechanisms to overcome the effect of IFN response during virus infection. url: https://api.elsevier.com/content/article/pii/S0042682217304427 doi: 10.1016/j.virol.2017.12.028 id: cord-319501-a2x1hvkk author: Wong, Lok-Yin Roy title: A molecular arms race between host innate antiviral response and emerging human coronaviruses date: 2016-01-15 words: 7759.0 sentences: 460.0 pages: flesch: 51.0 cache: ./cache/cord-319501-a2x1hvkk.txt txt: ./txt/cord-319501-a2x1hvkk.txt summary: Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. This suggests SARS-CoV N may interfere with RNA recognition by host immune sensors such as RIG-I and MDA5 thus achieving suppressive role in IFN production. Our group demonstrated that MERS-CoV ORF4a interacts with PACT, a cellular dsRNA-binding protein that optimally activates RIG-Iand MDA5-induced type I IFN production, in an RNAdependent manner (Siu et al., 2014c) . Infection with SARS-CoV and MERS-CoV has been accompanied with suppression of innate immune response, most notably with the suppression of type I IFN production and signaling pathways. Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses pact-induced activation of RIG-I and MDA5 in the innate antiviral response abstract: Coronaviruses have been closely related with mankind for thousands of years. Communityacquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived. [Image: see text] url: https://doi.org/10.1007/s12250-015-3683-3 doi: 10.1007/s12250-015-3683-3 id: cord-343963-99rd3o79 author: Wong, Mun-Teng title: Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection date: 2014-12-29 words: 17253.0 sentences: 1074.0 pages: flesch: 42.0 cache: ./cache/cord-343963-99rd3o79.txt txt: ./txt/cord-343963-99rd3o79.txt summary: 13, 14 Upon infection by viruses such as HCV, viral RNA is first sensed by cellular pattern recognition receptors (PRRs), and the PRR-mediated recruitment of adaptor proteins and the activation of downstream signaling lead to IFN production. First, we briefly discuss the signaling triggered by the retinoic acid-inducible gene 1-like receptor (RLR) and the Toll-like receptor (TLR), which leads to type I IFN synthesis and IFN-mediated signaling pathway activation, resulting in the expression of a variety of effector ISGs. We also summarize the strategies that HCV uses to escape IFN antiviral surveillance. 156 demonstrated that HCVinduced SG formation is IFN-and PKR-dependent and is inversely correlated with the induction of ISG proteins, such as myxovirus resistance gene A (MxA) and Ub-like (UBL)specific protease 18 (USP18), in HCV-infected cells without affecting the mRNA levels of these ISGs. Furthermore, the SG proteins TIA-1, TIAR and G3BP1 have been shown to play a critical role in HCV replication and infectious virus production. abstract: Infection with hepatitis C virus (HCV), a major viral cause of chronic liver disease, frequently progresses to steatosis and cirrhosis, which can lead to hepatocellular carcinoma. HCV infection strongly induces host responses, such as the activation of the unfolded protein response, autophagy and the innate immune response. Upon HCV infection, the host induces the interferon (IFN)-mediated frontline defense to limit virus replication. Conversely, HCV employs diverse strategies to escape host innate immune surveillance. Type I IFN elicits its antiviral actions by inducing a wide array of IFN-stimulated genes (ISGs). Nevertheless, the mechanisms by which these ISGs participate in IFN-mediated anti-HCV actions remain largely unknown. In this review, we first outline the signaling pathways known to be involved in the production of type I IFN and ISGs and the tactics that HCV uses to subvert innate immunity. Then, we summarize the effector mechanisms of scaffold ISGs known to modulate IFN function in HCV replication. We also highlight the potential functions of emerging ISGs, which were identified from genome-wide siRNA screens, in HCV replication. Finally, we discuss the functions of several cellular determinants critical for regulating host immunity in HCV replication. This review will provide a basis for understanding the complexity and functionality of the pleiotropic IFN system in HCV infection. Elucidation of the specificity and the mode of action of these emerging ISGs will also help to identify novel cellular targets against which effective HCV therapeutics can be developed. url: https://www.ncbi.nlm.nih.gov/pubmed/25544499/ doi: 10.1038/cmi.2014.127 id: cord-306533-lvm11o4r author: Woo, Bean title: Regulatory interplay between deubiquitinating enzymes and cytokines date: 2019-06-08 words: 7585.0 sentences: 449.0 pages: flesch: 49.0 cache: ./cache/cord-306533-lvm11o4r.txt txt: ./txt/cord-306533-lvm11o4r.txt summary: DUBs interact with some of the key molecules in the IFN signaling pathway, which include, but are not limited to, RIG-I, stimulator of interferon genes (STING), tumor necrosis factor receptor-associated factors (TRAFs), interferon regulatory factor are summarized in Table 1 . A study conducted using human kidney mesangial cells (MC) showed slightly different results: silencing CYLD in MC cells and stimulating them with poly IC increased the toll-like receptor 3 (TLR3)-induced activation of RIG-I and MDA5 [26] ; however, the level of mRNA of RIG-I and MDA5 actually decreased [26] . However, when USP18 -/-MEF cells with either WT USP18 or DUB activity-mutated USP18 were induced with HSV-1, HCMV or cytosolic DNA, Ifnb, Ifna4, Tnf, IL-6 or Cxcl1 genes increased in expression, indicating that the deubiquitinating activity of USP18 is not responsible for this phenomenon [41] . In a study by Malakhova et al., USP18 inhibited IFN-induced gene activation by affecting JAK-STAT signaling pathway in 293 T cells [44] . abstract: Deubiquitinating enzymes (DUBs) are cysteine protease proteins that reverse the ubiquitination by removing ubiquitins from the target protein. With over 100 DUBs identified and categorized into at least 7 families, many DUBs interact with one or more cytokines, influencing cellular processes, such as antiviral responses, inflammatory responses, apoptosis, etc. While some DUBs influence cytokine pathway or production, some DUBs are cytokine-inducible. In this article, we summarize a list of DUBs, their interaction with cytokines, target proteins and mechanisms of action. url: https://www.ncbi.nlm.nih.gov/pubmed/31208841/ doi: 10.1016/j.cytogfr.2019.06.001 id: cord-255607-dbexsugq author: Wu, Yang title: Porcine Epidemic Diarrhea Virus nsp15 Antagonizes Interferon Signaling by RNA Degradation of TBK1 and IRF3 date: 2020-05-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine epidemic diarrhea virus (PEDV) causes a porcine disease associated with swine epidemic diarrhea. The type I interferon (IFN-I or IFN α/β) is a key mediator of innate antiviral response during virus infection. Different antagonistic strategies have been identified and determined as to how PEDV infection inhibits the host’s IFN responses to escape the host innate immune pathway, but the pathogenic mechanisms of PEDV infection are not fully elucidated. Our preliminary results revealed that endogenous TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3), the key components in the IFN signaling pathway were downregulated in PEDV infected IPEC-J2 cells by iTRAQ analysis. In this study, we screened nsp15 as the most important viral encoded protein involved in TBK1 and IRF3 reduction. Endoribonuclease (EndoU) activity has been well determined for coronavirus nsp15. Three residues (H226, H241, and K282) of PEDV nsp15 were identified as critical amino acids for PEDV EndoU but not D265, which was not well correlated with published results of other coronaviruses, such as severe acute respiratory syndrome virus (SARS-CoV). Moreover, PEDV nsp15 can directly degrade the RNA levels of TBK1 and IRF3 dependent on its EndoU activity to suppress IFN production and constrain the induction of IFN stimulated genes (ISGs), by which PEDV antagonizes the host innate response to facilitate its replication. Collectively, these results have confirmed that PEDV nsp15 was capable of subverting the IFN response by the RNA degradation of TBK1 and IRF3. url: https://doi.org/10.3390/v12060599 doi: 10.3390/v12060599 id: cord-003300-994731g9 author: Wuerth, Jennifer Deborah title: NSs Protein of Sandfly Fever Sicilian Phlebovirus Counteracts Interferon (IFN) Induction by Masking the DNA-Binding Domain of IFN Regulatory Factor 3 date: 2018-11-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Sandfly fever Sicilian virus (SFSV) is one of the most widespread and frequently identified members of the genus Phlebovirus (order Bunyavirales, family Phenuiviridae) infecting humans. Being transmitted by Phlebotomus sandflies, SFSV causes a self-limiting, acute, often incapacitating febrile disease (“sandfly fever,” “Pappataci fever,” or “dog disease”) that has been known since at least the beginning of the 20th century. We show that, similarly to other pathogenic phleboviruses, SFSV suppresses the induction of the antiviral type I interferon (IFN) system in an NSs-dependent manner. SFSV NSs interfered with the TBK1-interferon regulatory factor 3 (IRF3) branch of the RIG-I signaling pathway but not with NF-κB activation. Consistently, we identified IRF3 as a host interactor of SFSV NSs. In contrast to IRF3, neither the IFN master regulator IRF7 nor any of the related transcription factors IRF2, IRF5, and IRF9 were bound by SFSV NSs. In spite of this specificity for IRF3, NSs did not inhibit its phosphorylation, dimerization, or nuclear accumulation, and the interaction was independent of the IRF3 activation or multimerization state. In further studies, we identified the DNA-binding domain of IRF3 (amino acids 1 to 113) as sufficient for NSs binding and found that SFSV NSs prevented the association of activated IRF3 with the IFN-β promoter. Thus, unlike highly virulent phleboviruses, which either destroy antiviral host factors or sequester whole signaling chains into inactive aggregates, SFSV modulates type I IFN induction by directly masking the DNA-binding domain of IRF3. IMPORTANCE Phleboviruses are receiving increased attention due to the constant discovery of new species and the ongoing spread of long-known members of the genus. Outbreaks of sandfly fever were reported in the 19th century, during World War I, and during World War II. Currently, SFSV is recognized as one of the most widespread phleboviruses, exhibiting high seroprevalence rates in humans and domestic animals and causing a self-limiting but incapacitating disease predominantly in immunologically naive troops and travelers. We show how the nonstructural NSs protein of SFSV counteracts the upregulation of the antiviral interferon (IFN) system. SFSV NSs specifically inhibits promoter binding by IFN transcription factor 3 (IRF3), a molecular strategy which is unique among phleboviruses and, to our knowledge, among human pathogenic RNA viruses in general. This IRF3-specific and stoichiometric mechanism, greatly distinct from the ones exhibited by the highly virulent phleboviruses, correlates with the intermediate level of pathogenicity of SFSV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232482/ doi: 10.1128/jvi.01202-18 id: cord-298131-zolwjl9u author: Xiao, Shuqi title: Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing date: 2010-06-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine reproductive and respiratory syndrome (PRRS) has been one of the most economically important diseases affecting swine industry worldwide and causes great economic losses each year. PRRS virus (PRRSV) replicates mainly in porcine alveolar macrophages (PAMs) and dendritic cells (DCs) and develops persistent infections, antibody-dependent enhancement (ADE), interstitial pneumonia and immunosuppression. But the molecular mechanisms of PRRSV infection still are poorly understood. Here we report on the first genome-wide host transcriptional responses to classical North American type PRRSV (N-PRRSV) strain CH 1a infection using Solexa/Illumina's digital gene expression (DGE) system, a tag-based high-throughput transcriptome sequencing method, and analyse systematically the relationship between pulmonary gene expression profiles after N-PRRSV infection and infection pathology. Our results suggest that N-PRRSV appeared to utilize multiple strategies for its replication and spread in infected pigs, including subverting host innate immune response, inducing an anti-apoptotic and anti-inflammatory state as well as developing ADE. Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. N-PRRSV-induced immunosuppression might be mediated by apoptosis of infected cells, which caused depletion of immune cells and induced an anti-inflammatory cytokine response in which they were unable to eradicate the primary infection. Our systems analysis will benefit for better understanding the molecular pathogenesis of N-PRRSV infection, developing novel antiviral therapies and identifying genetic components for swine resistance/susceptibility to PRRS. url: https://www.ncbi.nlm.nih.gov/pubmed/20614006/ doi: 10.1371/journal.pone.0011377 id: cord-329618-kywhulpc author: Xu, Cheng title: A de novo transcriptome analysis shows that modulation of the JAK-STAT signaling pathway by salmonid alphavirus subtype 3 favors virus replication in macrophage/dendritic-like TO-cells date: 2016-05-23 words: 8323.0 sentences: 426.0 pages: flesch: 55.0 cache: ./cache/cord-329618-kywhulpc.txt txt: ./txt/cord-329618-kywhulpc.txt summary: To elucidate the effect of type I IFN on the Jak/stat pathway in salmonid alphavirus subtype 3 (SAV3) infected macrophage/dendritic like TO-cells derived from Atlantic salmon (Salmo salar L) headkidney leukocytes, we used a differential transcriptome analysis by RNA-seq and the Kyoto encyclopedia of genes and genomes (KEGGs) pathway analysis to generate a repertoire of de novo assembled genes from type I IFN treated and non-treated TO-cells infected with SAV3. CONCLUSION: Data presented in this study shows that SAV3 infection downregulates several genes of the Jak/stat pathway, which could be an immune evasion strategy, used to block the transcription of antiviral genes that would interfere with SAV3 replication in TO-cells. Hence, in this study we used the KEGG pathway analysis software which is a third generation PT based software to identify networks of genes that form the Jak/stat signaling pathway from a de novo assembled transcriptome with the aim to better understand the modulation of genes expressed by TO cells infected with SAV3. abstract: BACKGROUND: The Janus kinase (Jak) and signaling transducer activator of transcription (Stat) pathway mediates the signaling of genes required for cellular development and homeostasis. To elucidate the effect of type I IFN on the Jak/stat pathway in salmonid alphavirus subtype 3 (SAV3) infected macrophage/dendritic like TO-cells derived from Atlantic salmon (Salmo salar L) headkidney leukocytes, we used a differential transcriptome analysis by RNA-seq and the Kyoto encyclopedia of genes and genomes (KEGGs) pathway analysis to generate a repertoire of de novo assembled genes from type I IFN treated and non-treated TO-cells infected with SAV3. RESULTS: Concurrent SAV3 infection with type I IFN treatment of TO-cells suppressed SAV3 structural protein (SP) expression by 2log(10) at 2 days post infection compared to SAV3 infection without IFN treatment which paved way to evaluating the impact of type I IFN on expression of Jak/stat pathway genes in SAV3 infected TO-cells. In the absence of type I IFN treatment, SAV3 downregulated several Jak/stat pathway genes that included type I and II receptor genes, Jak2, tyrosine kinase 2 (Tyk2), Stat3 and Stat5 pointing to possible failure to activate the Jak/stat signaling pathway and inhibition of signal transducers caused by SAV3 infection. Although the suppressor of cytokine signaling (SOCS) genes 1 and 3 were upregulated in the IFN treated cells, only SOCS3 was downregulated in the SAV3 infected cells which points to inhibition of SOCS3 by SAV3 infection in TO-cells. CONCLUSION: Data presented in this study shows that SAV3 infection downregulates several genes of the Jak/stat pathway, which could be an immune evasion strategy, used to block the transcription of antiviral genes that would interfere with SAV3 replication in TO-cells. Overall, we have shown that combining de novo assembly with pathway based transcriptome analyses provides a contextual approach to understanding the molecular networks of genes that form the Jak/stat pathway in TO-cells infected by SAV3. url: https://doi.org/10.1186/s12864-016-2739-6 doi: 10.1186/s12864-016-2739-6 id: cord-342800-62jklwiy author: Xu, Shuqin title: mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection date: 2020-09-09 words: 13579.0 sentences: 706.0 pages: flesch: 43.0 cache: ./cache/cord-342800-62jklwiy.txt txt: ./txt/cord-342800-62jklwiy.txt summary: The RNActive ® vaccine platform designed by CureVac used co-delivered RNA and protamine complex as the adjuvant to induce Th1 T cell responses, and naked, unmodified, and sequence-optimized mRNA as the antigen to develop mRNA vaccines [54] . used LNP to deliver self-amplified RNA vaccines, which caused the mRNA expression level in mice to be significantly higher than that of naked mRNA, CD4 + , and CD8 + T cell immune responses were also effectively induced. Overall development steps of those vaccines are (1) constructing the core antigen-encoding mRNA sequence optimized or combined based on selected antigen(s) from the target pathogen; (2) trying and choosing a proper combination of mRNA construction type, adjuvants, carrier materials and the route of administration; (3) detecting in vivo expression of the encoded antigen and the level of elicited immune responses; (4) providing research and demonstrations of immune induction mechanisms. abstract: Messenger ribonucleic acid (mRNA)-based drugs, notably mRNA vaccines, have been widely proven as a promising treatment strategy in immune therapeutics. The extraordinary advantages associated with mRNA vaccines, including their high efficacy, a relatively low severity of side effects, and low attainment costs, have enabled them to become prevalent in pre-clinical and clinical trials against various infectious diseases and cancers. Recent technological advancements have alleviated some issues that hinder mRNA vaccine development, such as low efficiency that exist in both gene translation and in vivo deliveries. mRNA immunogenicity can also be greatly adjusted as a result of upgraded technologies. In this review, we have summarized details regarding the optimization of mRNA vaccines, and the underlying biological mechanisms of this form of vaccines. Applications of mRNA vaccines in some infectious diseases and cancers are introduced. It also includes our prospections for mRNA vaccine applications in diseases caused by bacterial pathogens, such as tuberculosis. At the same time, some suggestions for future mRNA vaccine development about storage methods, safety concerns, and personalized vaccine synthesis can be found in the context. url: https://www.ncbi.nlm.nih.gov/pubmed/32916818/ doi: 10.3390/ijms21186582 id: cord-013280-kczj24se author: Yang, Bo title: Molecular Mechanisms of Immune Escape for Foot-and-Mouth Disease Virus date: 2020-09-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Foot-and-mouth disease virus (FMDV) causes a highly contagious vesicular disease in cloven-hoofed livestock that results in severe consequences for international trade, posing a great economic threat to agriculture. The FMDV infection antagonizes the host immune responses via different signaling pathways to achieve immune escape. Strategies to escape the cell immune system are key to effective infection and pathogenesis. This review is focused on summarizing the recent advances to understand how the proteins encoded by FMDV antagonize the host innate and adaptive immune responses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558374/ doi: 10.3390/pathogens9090729 id: cord-295508-yhdj5m0e author: Yang, Li-Tao title: Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients date: 2006-06-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The role of cell-mediated immunity in human SARS-CoV infection is still not well understood. In this study, we found that memory T-cell responses against the spike (S) protein were persistent for more than 1 year after SARS-CoV infection by detecting the production of IFN-γ using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4(+) and CD8(+) T cells were involved in cellular responses against SARS-CoV infection. Interestingly, most of SARS-CoV S-specific memory CD4(+) T cells were central memory cells expressing CD45RO(+) CCR7(+) CD62L(−). However, the majority of memory CD8(+) T cells revealed effector memory phenotype expressing CD45RO(−) CCR7(−) CD62L(−). Thus, our study provides the evidence that SARS-CoV infection in humans can induce cellular immune response that is persistent for a long period of time. These data may have an important implication in the possibility of designing effective vaccine against SARS-CoV infection, specifically in defining T-cell populations that are implicated in protective immunity. url: https://www.sciencedirect.com/science/article/pii/S1521661606007352 doi: 10.1016/j.clim.2006.05.002 id: cord-307813-elom30nx author: Yip, Tsz-Fung title: Advancements in Host-Based Interventions for Influenza Treatment date: 2018-07-10 words: 15075.0 sentences: 735.0 pages: flesch: 38.0 cache: ./cache/cord-307813-elom30nx.txt txt: ./txt/cord-307813-elom30nx.txt summary: Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. A recent study using RNAi also demonstrated that cholesterol homeostasis can be regulated via acid phosphatase 2 (ACP2)-mediated Niemann-Pick C2 activity and impaired the membrane fusion of IAV and influenza B virus (IBV) (52) , further suggesting the importance of controlling cholesterol homeostasis in the release of viral genome to cytoplasm. Furthermore, FPR2 antagonists have been described to possess antiviral activity against not only IAV but also IBV infection (111) , promoting the idea that antagonizing FPR2 to suppress Raf/MEK/ERK signaling cascade could potentially be a novel approach for the treatment of a broad spectrum of influenza viruses. abstract: Influenza is a major acute respiratory infection that causes mortality and morbidity worldwide. Two classes of conventional antivirals, M2 ion channel blockers and neuraminidase inhibitors, are mainstays in managing influenza disease to lessen symptoms while minimizing hospitalization and death in patients with severe influenza. However, the development of viral resistance to both drug classes has become a major public health concern. Vaccines are prophylaxis mainstays but are limited in efficacy due to the difficulty in matching predicted dominant viral strains to circulating strains. As such, other potential interventions are being explored. Since viruses rely on host cellular functions to replicate, recent therapeutic developments focus on targeting host factors involved in virus replication. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. In this review, we will discuss the advancements in novel host-based interventions for treating influenza disease. url: https://doi.org/10.3389/fimmu.2018.01547 doi: 10.3389/fimmu.2018.01547 id: cord-252485-cxi3cr15 author: Yoshida, Asuka title: IFN-β-inducing, unusual viral RNA species produced by paramyxovirus infection accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner date: 2015-08-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The interferon (IFN) system is one of the most important defensive responses of mammals against viruses, and is rapidly evoked when the pathogen-associated molecular patterns (PAMPs) of viruses are sensed. Non-self, virus-derived RNA species have been identified as the PAMPs of RNA viruses. In the present study, we compared different types of IFN-β-inducing and -non-inducing viruses in the context of Sendai virus infection. We found that some types of unusual viral RNA species were produced by infections with IFN-β-inducing viruses and accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner. One of these structures was similar to the so-called antiviral stress granules (avSGs) formed by an infection with IFN-inducing viruses whose C proteins were knocked-out or mutated. Non-encapsidated, unusual viral RNA harboring the 5′-terminal region of the viral genome as well as RIG-I and typical SG markers accumulated in these granules. Another was a non-SG-like inclusion formed by an infection with the Cantell strain; a copyback-type DI genome, but not an authentic viral genome, specifically accumulated in the inclusion, whereas RIG-I and SG markers did not. The induction of IFN-β was closely associated with the production of these unusual RNAs as well as the formation of the cytoplasmic structures. url: https://doi.org/10.3389/fmicb.2015.00804 doi: 10.3389/fmicb.2015.00804 id: cord-002238-fyztb8d9 author: Young, D. F. title: Human IFIT1 Inhibits mRNA Translation of Rubulaviruses but Not Other Members of the Paramyxoviridae Family date: 2016-09-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We have previously shown that IFIT1 is primarily responsible for the antiviral action of interferon (IFN) alpha/beta against parainfluenza virus type 5 (PIV5), selectively inhibiting the translation of PIV5 mRNAs. Here we report that while PIV2, PIV5, and mumps virus (MuV) are sensitive to IFIT1, nonrubulavirus members of the paramyxoviridae such as PIV3, Sendai virus (SeV), and canine distemper virus (CDV) are resistant. The IFIT1 sensitivity of PIV5 was not rescued by coinfection with an IFIT1-resistant virus (PIV3), demonstrating that PIV3 does not specifically inhibit the antiviral activity of IFIT1 and that the inhibition of PIV5 mRNAs is regulated by cis-acting elements. We developed an in vitro translation system using purified human IFIT1 to further investigate the mechanism of action of IFIT1. While the translations of PIV2, PIV5, and MuV mRNAs were directly inhibited by IFIT1, the translations of PIV3, SeV, and CDV mRNAs were not. Using purified human mRNA-capping enzymes, we show biochemically that efficient inhibition by IFIT1 is dependent upon a 5′ guanosine nucleoside cap (which need not be N7 methylated) and that this sensitivity is partly abrogated by 2′O methylation of the cap 1 ribose. Intriguingly, PIV5 M mRNA, in contrast to NP mRNA, remained sensitive to inhibition by IFIT1 following in vitro 2′O methylation, suggesting that other structural features of mRNAs may influence their sensitivity to IFIT1. Thus, surprisingly, the viral polymerases (which have 2′-O-methyltransferase activity) of rubulaviruses do not protect these viruses from inhibition by IFIT1. Possible biological consequences of this are discussed. IMPORTANCE Paramyxoviruses cause a wide variety of diseases, and yet most of their genes encode structural proteins and proteins involved in their replication cycle. Thus, the amount of genetic information that determines the type of disease that paramyxoviruses cause is relatively small. One factor that will influence disease outcomes is how they interact with innate host cell defenses, including the interferon (IFN) system. Here we show that different paramyxoviruses interact in distinct ways with cells in a preexisting IFN-induced antiviral state. Strikingly, all the rubulaviruses tested were sensitive to the antiviral action of ISG56/IFIT1, while all the other paramyxoviruses tested were resistant. We developed novel in vitro biochemical assays to investigate the mechanism of action of IFIT1, demonstrating that the mRNAs of rubulaviruses can be directly inhibited by IFIT1 and that this is at least partially because their mRNAs are not correctly methylated. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5044818/ doi: 10.1128/jvi.01056-16 id: cord-265723-6k8196p2 author: Yu, Chengjun title: Evaluation of safety, efficacy, tolerability, and treatment-related outcomes of type I interferons for Human coronaviruses (HCoVs) infection in clinical practice: An updated critical systematic review and meta-analysis date: 2020-06-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: There is no vaccine or specific antiviral treatment for HCoVs infection. The use of type I interferons for coronavirus is still under great debate in clinical practice. MATERIALS AND METHODS: A literature search of all relevant studies published on PubMed, Cochrane library, Web of Science database, Science Direct, Wanfang Data, and China National Knowledge Infrastructure (CNKI) until February 2020 was performed. RESULTS: Of the 1081 identified articles, only 15 studies were included in the final analysis. Comorbidities and delay in diagnosis were significantly associated with case mortality. Type I interferons seem to improve respiratory distress, relieve lung abnormalities, present better saturation, reduce needs for supplemental oxygen support. Type I interferons seem to be well tolerated, and don’t increase life threating adverse effects. Data on IFNs in HCoVs are limited, heterogenous and mainly observational. CONCLUSIONS: Current data do not allow making regarding robust commendations for the use of IFNs in HCoVs in general or in specific subtype. But we still recommend type I interferons serving as first-line antivirals in HCoVs infections within local protocols, and interferons may be adopted to the treatments of the SARS-CoV-2 as well. Well-designed large-scale prospective randomized control trials are greatly needed to provide more robust evidence on this topic. url: https://www.sciencedirect.com/science/article/pii/S1567576920315526?v=s5 doi: 10.1016/j.intimp.2020.106740 id: cord-351489-tzmev77c author: Yuan, Shuofeng title: Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19) date: 2020-06-10 words: 5002.0 sentences: 238.0 pages: flesch: 40.0 cache: ./cache/cord-351489-tzmev77c.txt txt: ./txt/cord-351489-tzmev77c.txt summary: They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. In this primary screening, chloroquine, lopinavir, and remdesivir which were recently reported to have anti-SARS-CoV-2 activity, exhibited about 1.3-2.0 log10 copies/mL reduction in viral RNA load ( Figure 1 ). In comparison, recombinant IFN-β demonstrated the most potent anti-SARS-CoV-2 activity, with Avonex (IFN-β1a), Rebif (IFN-β1a), and Betaferon (IFN-β1b) each achieving about 3 log10 copies/mL reduction in viral load. In our primary screening using a fixed antiviral agent concentration and virus inoculum, we identified recombinant IFNs and lipogenesis modulators to be the most potent anti-SARS-CoV-2 agents among 22 broad-spectrum antivirals. abstract: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-β1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC(50) at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials. url: https://www.ncbi.nlm.nih.gov/pubmed/32532085/ doi: 10.3390/v12060628 id: cord-263141-n200x6z1 author: Zelaya, Hortensia title: Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection date: 2016-12-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation–coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract. url: https://www.ncbi.nlm.nih.gov/pubmed/28066442/ doi: 10.3389/fimmu.2016.00633 id: cord-256816-gd7y3ggj author: Zhang, Can title: Grass carp reovirus VP56 represses interferon production by degrading phosphorylated IRF7 date: 2020-02-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Grass carp reovirus (GCRV) is an efficient pathogen causing high mortality in grass carp, meanwhile, fish interferon (IFN) is a powerful cytokine enabling host cells to establish an antiviral state; therefore, the strategies used by GCRV to escape the cellular IFN response need to be investigated. Here, we report that GCRV VP56 inhibits host IFN production by degrading the transcription factor IFN regulatory factor 7 (IRF7). First, overexpression of VP56 inhibited the IFN production induced by the polyinosinic-polycytidylic acid (poly I:C) and mitochondrial antiviral signaling protein (MAVS), while the capacity of IRF7 on IFN induction was unaffected. Second, VP56 interacted with RLRs but did not affect the stabilization of the proteins in the normal state, while the phosphorylated IRF7 activated by TBK1 was degraded by VP56 through K48-linked ubiquitination. Finally, overexpression of VP56 remarkably reduced the host cellular ifn transcription and facilitated viral proliferation. Taken together, our results demonstrate that GCRV VP56 suppresses the host IFN response by targeting phosphorylated IRF7 for ubiquitination and degradation. url: https://doi.org/10.1016/j.fsi.2020.02.004 doi: 10.1016/j.fsi.2020.02.004 id: cord-324674-yd7idp90 author: Zhang, Chengfei title: IFN-stimulated P2Y(13) protects mice from viral infection by suppressing the cAMP/EPAC1 signaling pathway date: 2018-08-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Among the most important sensors of extracellular danger signals, purinergic receptors have been demonstrated to play crucial roles in host defense against infection. However, the function of P2 receptors in viral infection has been little explored. Here we demonstrated that P2Y(13) and its ligand ADP play an important role in protecting hosts from viral infections. First, we demonstrate that P2Y(13), as a typical interferon-stimulated gene, is induced together with extracellular ADP during viral infection. Most importantly, extracellular ADP restricts the replication of different kinds of viruses, including vesicular stomatitis virus, Newcastle disease virus, herpes simplex virus 1, and murine leukemia virus. This kind of protection is dependent on P2Y(13) but not P2Y(1) or P2Y(12), which are also considered as receptors for ADP. Furthermore, cyclic adenosine monophosphate and EPAC1 are downregulated by extracellular ADP through the P2Y(13)-coupled Gi alpha subunit. Accordingly, inhibition or deletion of EPAC1 significantly eliminates ADP/P2Y(13)-mediated antiviral activities. Taken together, our results show that P2Y(13) and ADP play pivotal roles in the clearance of invaded virus and have the potential as antiviral targets. url: https://doi.org/10.1093/jmcb/mjy045 doi: 10.1093/jmcb/mjy045 id: cord-299549-bjqwwzam author: Zhang, Lei title: Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis date: 2015-01-01 words: 3644.0 sentences: 191.0 pages: flesch: 47.0 cache: ./cache/cord-299549-bjqwwzam.txt txt: ./txt/cord-299549-bjqwwzam.txt summary: When the viral infection proceeds to the terminal stage, the key factor would be applying a non-specific immune modulation approach to suppress the cytokine storm that causes multiple organ failure, in an attempt to open a time window for the host''s immune system to recover. In most patients, Ebola viral burden elevates by time and triggers an extremely strong immune attack-a phenomenon called ''cytokine storm'' (Sullivan et al., 2003) , during which monocytes and/or macrophages produce a massive amount of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukins (ILs), and The virus burden, inflammatory response, and specific antibodies are the main contributors to different outcomes: mortality, survival, or symptomless infection (Fig. 2) , suggesting that the appropriate intervention strategy in each stage would accordingly be able to control the Ebola virus. Nonetheless, this phenomenon does give clues to the treatment against Ebola virus disease (EVD)-early activated innate immune responses may prevent the viral infection. abstract: The 2014 Ebola outbreak in West Africa triggered a global crisis. Nine countries have reported more than 20 000 infection cases in total and nearly 8000 lives have been lost. The actual death toll is likely much higher than this figure; the death rate is as high as 70%, considering confirmed cases. The Ebola virus launches its destruction by shutting down the host’s innate and adaptive immune systems. The virus then replicates itself out of control and causes a cytokine storm in the host. Consequently, the host’s overdriven immune system attacks its own endothelial cells and this leads to multiple organ hemorrhagic damage, the host dies of septic shock finally. Under current circumstances where no specific interventions have shown effectiveness against the virus, our opinions are justified in applying a non-specific anti-viral approach during the incubation period of virus infection as an essential protection to put the host’s immune system into an alert state and henceforth to slow down the viral replication. When the viral infection proceeds to the terminal stage, the key factor would be applying a non-specific immune modulation approach to suppress the cytokine storm that causes multiple organ failure, in an attempt to open a time window for the host’s immune system to recover. url: https://www.ncbi.nlm.nih.gov/pubmed/25559950/ doi: 10.1631/jzus.b1400365 id: cord-322683-wkrj6n1d author: Zhang, Pengfei title: Cellular Poly(C) Binding Protein 2 Interacts with porcine epidemic diarrhea virus Papain-Like Protease 1 and Supports Viral Replication date: 2020-07-13 words: 4063.0 sentences: 276.0 pages: flesch: 57.0 cache: ./cache/cord-322683-wkrj6n1d.txt txt: ./txt/cord-322683-wkrj6n1d.txt summary: title: Cellular Poly(C) Binding Protein 2 Interacts with porcine epidemic diarrhea virus Papain-Like Protease 1 and Supports Viral Replication Taken together, these data demonstrated that PLP1 negatively regulated the production of type 1 interferon by interacting with PCBP2 and promoted PEDV replication. The PEDV N protein interacts with the TANK-binding kinase, blocking its association with interferon regulatory factor 3 (IRF3) and thus inhibiting IRF3 activation and type I IFN production (Ding et al., 2014; Hu et al., 2018) . PCBP2 expression is induced following viral infection and acts as a negative regulator of mitochondrial antiviral signaling protein (MAVS), triggering its degradation (You et al., 2009) . Although significant progress has been made in understanding PEDV evasion of innate immune responses, the mechanism of interaction between viral and host cell proteins remains unclear. In the present study, we demonstrated that PLP1 interacted with PCBP2 to inhibit IFN-β production and promote PEDV replication. abstract: Porcine epidemic diarrhea virus (PEDV) belongs to the Alphacoronavirus genus in the Coronaviridae family. Similar to other coronaviruses, PEDV encodes two papain-like proteases. Papain-like protease (PLP)2 has been proposed to play a key role in antagonizing host innate immunity. However, the function of PLP1 remains unclear. In this study, we found that overexpression of PLP1 significantly promoted PEDV replication and inhibited production of interferon-β. Immunoprecipitation and mass spectrometry were used to identify cellular interaction partners of PLP1. Host cell poly(C) binding protein 2 (PCBP2) was determined to bind and interact with PLP1. Both endogenous and overexpressed PCBP2 co-localized with PLP1 in the cytoplasm. Overexpression of PLP1 upregulated expression of PCBP2. Furthermore, overexpression of PCBP2 promoted PEDV replication. Silencing of endogenous PCBP2 using small interfering RNAs attenuated PEDV replication. Taken together, these data demonstrated that PLP1 negatively regulated the production of type 1 interferon by interacting with PCBP2 and promoted PEDV replication. url: https://api.elsevier.com/content/article/pii/S0378113520302698 doi: 10.1016/j.vetmic.2020.108793 id: cord-255773-b4re5bky author: Zhang, Qingzhan title: Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1 date: 2016-01-14 words: 9880.0 sentences: 584.0 pages: flesch: 52.0 cache: ./cache/cord-255773-b4re5bky.txt txt: ./txt/cord-255773-b4re5bky.txt summary: title: Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1 We showed that PEDV suppressed the type I interferon production and ISGs expression in these cells, and identified nsp1, nsp3, nsp7, nsp14, nsp15, nsp16, E, M, N and ORF3 as the viral IFN antagonists. The CBP degradation is a novel mechanism of coronavirus nsp1 for IFN suppression and our study provides a new insight into the immune modulation and evasion strategy of PEDV. MARC-145 cells have been used to study type I IFN signaling of porcine arterivirus (Kim et al., 2010; Overend et al., 2007; Patel et al., 2010) , and thus infection of these cells One μg of each of the cloned genes was transfected to HeLa cells in 12-well plates, and protein expression was determined by immunofluorescence (B) and abstract: Type I interferons (IFN-α/β) are the major components of the innate immune response of hosts, and in turn many viruses have evolved to modulate the host response during infection. We found that the IFN-β production was significantly suppressed during PEDV infection in cells. To identify viral IFN antagonists and to study their suppressive function, viral coding sequences for the entire structural and nonstructural proteins were cloned and expressed. Of 16 PEDV nonstructural proteins (nsps), nsp1, nsp3, nsp7, nsp14, nsp15 and nsp16 were found to inhibit the IFN-β and IRF3 promoter activities. The sole accessory protein ORF3, structure protein envelope (E), membrane (M), and nucleocapsid (N) protein were also shown to inhibit such activities. PEDV nsp1 did not interfere the IRF3 phosphorylation and nuclear translocation but interrupted the enhanceosome assembly of IRF3 and CREB-binding protein (CBP) by degrading CBP. A further study showed that the CBP degradation by nsp1 was proteasome-dependent. Our data demonstrate that PEDV modulates the host innate immune responses by degrading CBP and suppressing ISGs expression. url: https://api.elsevier.com/content/article/pii/S0042682215005310 doi: 10.1016/j.virol.2015.12.010 id: cord-000403-vzbh457k author: Zhang, Weijun title: Identification of CD8(+ )cytotoxic T lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in BALB/c mice date: 2011-05-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Twenty-seven nanopeptides derived from the matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were screened for their ability to elicit a recall interferon-γ (IFN-γ) response from the splenocytes of BALB/c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus rWR-PRRSV-M. We identified two peptides (amino acid residues K(93)FITSRCRL and F(57)GYMTFVHF) as CD8(+ )cytotoxic T lymphocyte (CTL) epitopes. These peptides elicited significant numbers of IFN-γ secreting cells, compared with other M nonapeptides and one irrelevant nonapeptide. Bioinformatics analysis showed that the former is an H-2K(d)-restricted CTL epitope, and the latter is an H-2D(d)-restricted CTL epitope. Multiple amino acid sequence alignment among different PRRSV M sequences submitted to GenBank indicated that these two CTL epitopes are strongly conserved, and they should therefore be considered for further research on the mechanisms of cellular immune responses to PRRSV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126774/ doi: 10.1186/1743-422x-8-263 id: cord-318070-8txogxek author: Zhang, Xiao-Nan title: Hyper-activated IRF-1 and STAT1 contribute to enhanced Interferon stimulated gene (ISG) expression by Interferon α and γ co-treatment in human hepatoma cells date: 2006-09-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Previous reports suggest that type I and type II Interferon can co-operatively inhibit some virus replication, e.g. HCV, SARS-CoV, HSV-1. To find out the molecular mechanism underlying this phenomenon, we analyzed the transcription profile stimulated by IFN-α and IFN-γ in Huh-7 cells and found that the transcription of a subset of IFN stimulated genes (ISGs) including BclG, XAF1, TRAIL and TAP1 was enhanced when IFN-α and γ were both present. Promoter analysis of BclG revealed that IRF-1 and STAT1 were both required in this process. Enhanced IRF-1/DNA complex formation was observed in interferon co-treatment group by gel shift analysis. Furthermore, IRF-1 activation was found to be generally required in this cluster of ISGs. STAT1 tyrosine phosphorylation was elevated by IFN combination treatment, however, only the hyper-transactivation of GAS but not ISRE was observed. In conclusion, hyper-activation of IRF-1 and elevated STAT1 dimer formation may be two general switches which contribute to a much more robust antiviral symphony against virus replication when type I and type II IFNs are co-administered. url: https://www.sciencedirect.com/science/article/pii/S0167478106001175 doi: 10.1016/j.bbaexp.2006.08.003 id: cord-258286-lodjcj8c author: Zhang, Xuming title: Expression of Interferon-γ by a Coronavirus Defective-Interfering RNA Vector and Its Effect on Viral Replication, Spread, and Pathogenicity date: 1997-07-07 words: 5866.0 sentences: 296.0 pages: flesch: 54.0 cache: ./cache/cord-258286-lodjcj8c.txt txt: ./txt/cord-258286-lodjcj8c.txt summary: Previous studies have shown that immunocoma large plaque variant derived from the parental JHM petent mice infected with MHV exhibited increased exstrain (Stohlman et al., 1982) ; the small plaque variant pression of a number of cytokines, including IL-1, IL-6, DS (Stohlman et al., 1982) ; the neutralization-escape mu-TNF-a, and IFN-g, in the CNS at the time of viral cleartant 2.2-V-1 (Fleming et al., 1987; Wang et al., 1992) , and ance (Pearce et al., 1994) . The expressed IFNg exhibited antiviral activity, prevented virus spread in layers of DBT cells grown at approximately 70% confluence in 60-mm petri dishes were infected with MHV at vitro, and altered viral pathogenesis in mice. Expression of IFN-g using an MHV DI RNA vector cell metabolism prior to infection or it may be that interferon acts at an early stage of viral replication. abstract: Abstract A defective-interfering (DI) RNA of the murine coronavirus mouse hepatitis virus (MHV) was developed as a vector for expressing interferon-γ (IFN-γ). The murine IFN-γ gene was cloned into the DI vector under the control of an MHV transcriptional promoter and transfected into MHV-infected cells. IFN-γ was secreted into culture medium as early as 6 hr posttransfection and reached a peak level (up to 180 U/ml) at 12 hr posttransfection. The DI-expressed IFN-γ (DE-IFN-γ) exhibited an antiviral activity comparable to that of recombinant IFN-γ and was blocked by a neutralizing monoclonal antibody against IFN-γ. Treatment of macrophages with DE-IFN-γ selectively induced the expression of the cellular inducible nitric oxide synthase and the IFN-γ-inducing factor (IGIF) but did not affect the amounts of the MHV receptor mRNA. Antiviral activity was detected only when cells were pretreated with IFN-γ for 24 hr prior to infection; no inhibition of virus replication was detected when cells were treated with IFN-γ during or after infection. Furthermore, addition of IFN-γ together with MHV did not prevent infection, but appeared to prevent subsequent viral spread. MHV variants with different degrees of neurovirulence in mice had correspondingly different levels of sensitivities to IFN-γ treatmentin vitro,with the most virulent strain being most resistant to IFN-γ treatment. Infection of susceptible mice with DE-IFN-γ-containing virus caused significantly milder disease, accompanied by more pronounced mononuclear cell infiltrates into the CNS and less virus replication, than that caused by virus containing a control DI vector. This study thus demonstrates the feasibility and usefulness of this MHV DI vector for expressing cytokines and may provide a model for studying the role of cytokines in MHV pathogenesis. url: https://api.elsevier.com/content/article/pii/S0042682297985986 doi: 10.1006/viro.1997.8598 id: cord-011438-imbpgsub author: Zhang, Yun title: Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection date: 2020-03-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza A viruses (IAVs) are highly contagious pathogens infecting human and numerous animals. The viruses cause millions of infection cases and thousands of deaths every year, thus making IAVs a continual threat to global health. Upon IAV infection, host innate immune system is triggered and activated to restrict virus replication and clear pathogens. Subsequently, host adaptive immunity is involved in specific virus clearance. On the other hand, to achieve a successful infection, IAVs also apply multiple strategies to avoid be detected and eliminated by the host immunity. In the current review, we present a general description on recent work regarding different host cells and molecules facilitating antiviral defenses against IAV infection and how IAVs antagonize host immune responses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232439/ doi: 10.3390/v12040376 id: cord-313445-4v7pjqt2 author: Zhao, Jun title: Porcine interferon lambda 3 (IFN-λ3) shows potent anti-PRRSV activity in primary porcine alveolar macrophages (PAMs) date: 2020-10-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a serious viral disease of swine. At present, there are vaccines for the control of PRRSV infection, but the effect is not satisfactory. The recombination of attenuated vaccines causes significant difficulties with the prevention and control of PRRSV. Type III interferons (IFNs), also called IFN-λs, were newly identified and showed potent antiviral activity within the mucosal surface and immune organs. RESULTS: Therefore, primary porcine alveolar macrophages (PAMs) were used for this investigation. To this end, we found that the replication of PRRSV in PAMs was significantly reduced after pre-treatment with IFN-λ3, and such inhibition was dose- and time-dependent. The plaque formation of PRRSV abrogated entirely, and virus yields were reduced by four orders of magnitude when the primary PAMs were treated with IFN-λ3 at 1000 ng/ml. In addition, IFN-λ3 in our study was able to induce the expression of interferon-stimulated genes 15 (ISG15), 2′-5′-oligoadenylate synthase 1 (OAS1), IFN-inducible transmembrane 3 (IFITM3), and myxoma resistance protein 1(Mx1) in primary PAMs. CONCLUSIONS: IFN-λ3 had antiviral activity against PRRSV and can stimulate the expression of pivotal interferon-stimulated genes (ISGs), i.e., ISG15, Mx1, OAS1, and IFITM3. So, IFN-λ3 may serve as a useful antiviral agent. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-020-02627-6. url: https://www.ncbi.nlm.nih.gov/pubmed/33115475/ doi: 10.1186/s12917-020-02627-6 id: cord-025181-eg108wcd author: Zheng, Zhihang title: Establishment of Murine Infection Models with Biological Clones of Dengue Viruses Derived from a Single Clinical Viral Isolate date: 2020-05-25 words: 5919.0 sentences: 340.0 pages: flesch: 59.0 cache: ./cache/cord-025181-eg108wcd.txt txt: ./txt/cord-025181-eg108wcd.txt summary: In this study, with biologically cloned viruses from a single clinical isolate, we have established two mouse models of DENV infection, one is severe lethal infection in immunocompromised mice, and the other resembles self-limited disease manifestations in Balb/c mice with transient blockage of type I IFN responses. Further, we compared the infectivity of these two viral variants in a self-limited infection model, in which type I IFN receptor of wild-type Balb/c mice had been transiently blocked before infection, and found only the virus strain exhibiting larger plaque size caused infectious viral particles in sera. We have recently developed a ZIKV infection model in Balb/c mice with transient blockage of type I IFN Fig. 2 Phylogenetic analysis of DENV-2 1D4-5-SP and DENV-2 8H2-7-LP with representative serotype-2 dengue viruses of different genotypes isolated from different geographical regions. abstract: Dengue virus (DENV) is a single-stranded RNA virus transmitted by mosquitoes in tropical and subtropical regions. It causes dengue fever, dengue hemorrhagic fever and dengue shock syndrome in patients. Each year, 390 million people are estimated to be infected by four serotypes of dengue virus, creating a great burden on global public health and local economy. So far, no antiviral drug is available for dengue disease, and the newly licensed vaccine is far from satisfactory. One large obstacle for dengue vaccine and drug development is the lack of suitable small animal models. Although some DENV infection models have been developed, only a small number of viral strains can infect immunodeficient mice. In this study, with biologically cloned viruses from a single clinical isolate, we have established two mouse models of DENV infection, one is severe lethal infection in immunocompromised mice, and the other resembles self-limited disease manifestations in Balb/c mice with transient blockage of type I IFN responses. This study not only offers new small animal models of dengue viral infection, but also provides new viral variants for further investigations on dengue viral pathogenesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246292/ doi: 10.1007/s12250-020-00229-y id: cord-276034-a8pixbuc author: Zhi, Yan title: Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein date: 2005-04-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The causative agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus, SARS-associated coronavirus (SARS-CoV). CD8 T cells play an important role in controlling diseases caused by other coronaviruses and in mediating vaccine-induced protective immunity in corresponding animal models. The spike protein, a main surface antigen of SARS-CoV, is one of the most important antigen candidates for vaccine design. Overlapping peptides were used to identify major histocompatibility complex class I-restricted epitopes in mice immunized with vectors encoding codon-optimized SARS-CoV spike protein. CD8 T-cell responses were mapped to two H-2(b)-restricted epitopes (S436–443 and S525–532) and one H-2(d)-restricted epitope (S366–374). The identification of these epitopes will facilitate the evaluation of vaccine strategies in murine models of SARS-CoV infection. Furthermore, codon and promoter optimizations can greatly enhance the overall immunogenicity of spike protein in the context of replication-defective human and simian adenoviral vaccine carriers. The optimized recombinant adenoviral vaccine vectors encoding spike can generate robust antigen-specific cellular immunity in mice and may potentially be useful for control of SARS-CoV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/15823604/ doi: 10.1016/j.virol.2005.01.050 id: cord-351520-c5fi2uoh author: Zhong, Bo title: Regulation of virus-triggered type I interferon signaling by cellular and viral proteins date: 2010-02-01 words: 10571.0 sentences: 637.0 pages: flesch: 46.0 cache: ./cache/cord-351520-c5fi2uoh.txt txt: ./txt/cord-351520-c5fi2uoh.txt summary: Recently, we and others identified a new adapter protein called mediator of IRF3 activation (MITA, also known as STING), which plays a critical role in virus-induced type I IFN expression (Ishikawa and Barber, 2008; Zhong et al., 2008) . abstract: Host pattern recognition receptors (PRRs) recognize invading viral pathogens and initiate a series of signaling cascades that lead to the expression of type I interferons (IFNs) and inflammatory cytokines. During the past decade, significant progresses have been made to characterize PRRs such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) and elucidate the molecular mechanisms of TLR- and RLR-mediated signaling. To avoid excessive and harmful immune effects caused by over-activation of these signaling pathways, host cells adopt a number of strategies to regulate them. In addition, invading viruses also employ a variety of mechanisms to inhibit the production of type I IFNs, thereby evading the supervision and clearance by the host. In this review, we briefly summarize the TLR- and RLR-mediated type I IFN signaling and then focus on the mechanisms by which host cellular and viral components regulate the expression of type I IFNs. url: https://doi.org/10.1007/s11515-010-0013-x doi: 10.1007/s11515-010-0013-x id: cord-278523-djjtgbh6 author: Zhou, Bei-xian title: β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling date: 2020-06-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: β-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of β-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that β-sitosterol (150–450 μg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of β-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, β-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of β-sitosterol (50, 200 mg·kg(−1)·d(−1), i.g., for 2 days) dose-dependently ameliorated IAV-mediated recruitment of pathogenic cytotoxic T cells and immune dysregulation. In addition, pre-administration of β-sitosterol protected mice from lethal IAV infection. Our data suggest that β-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza. url: https://doi.org/10.1038/s41401-020-0403-9 doi: 10.1038/s41401-020-0403-9 id: cord-327534-f2wvh6la author: Zhou, Peng title: IRF7 in the Australian Black Flying Fox, Pteropus alecto: Evidence for a Unique Expression Pattern and Functional Conservation date: 2014-08-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: As the only flying mammal, bats harbor a number of emerging and re-emerging viruses, many of which cause severe diseases in humans and other mammals yet result in no clinical symptoms in bats. As the master regulator of the interferon (IFN)-dependent immune response, IFN regulatory factor 7 (IRF7) plays a central role in innate antiviral immunity. To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Our results demonstrate that bat IRF7 retains the ability to bind to MyD88 and activate the IFN response despite unique changes in the MyD88 binding domain. We also demonstrate that bat IRF7 has a unique expression pattern across both immune and non-immune related tissues and is inducible by double-strand RNA. The broad tissue distribution of IRF7 may provide bats with an enhanced ability to rapidly activate the IFN response in a wider range of tissues compared to other mammals. The importance of IRF7 in antiviral activity against the bat reovirus, Pulau virus was confirmed by siRNA knockdown of IRF7 in bat cells resulting in enhanced viral replication. Our results highlight the importance of IRF7 in innate antiviral immunity in bats. url: https://doi.org/10.1371/journal.pone.0103875 doi: 10.1371/journal.pone.0103875 id: cord-356197-js7l86fh author: Zhou, Ping title: Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo date: 2011-08-07 words: 4640.0 sentences: 219.0 pages: flesch: 40.0 cache: ./cache/cord-356197-js7l86fh.txt txt: ./txt/cord-356197-js7l86fh.txt summary: Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Genome-wide transcriptional responses of lungs of Landrace×Yorkshire crossbred piglets to a classical North American type PRRSV strain infection was analyzed by Solexa/Illumina''s Digital Gene Expression (DGE) System, which is a tag-based high-throughput transcriptome sequencing method [6] . This systematic analysis of the pulmonary gene expression profiles suggested that upregulation expression of pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during PRRSV infection processes [6] . Microarray analysis revealed that HP-PRRSV infection has affected PAMs in vivo in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) infects mainly the porcine alveolar macrophages (PAMs) and causes porcine reproductive and respiratory syndrome (PRRS). Previous studies have analyzed the global gene expression profiles of lung tissue in vivo and PAMs in vitro following infection with PRRSV, however, transcriptome-wide understanding of the interaction between highly pathogenic PRRSV (HP-PRRSV) and PAMs in vivo has not yet been established. In this study, we employed Affymetrix microarrays to investigate the gene expression patterns of PAMs isolated from Tongcheng piglets (a Chinese indigenous breed) after infection with HP-PRRSV. During the infection, Tongcheng piglets exhibited typical clinical signs, e.g. fever, asthma, coughing, anorexia, lethargy and convulsion, but displayed mild regional lung damage at 5 and 7 dpi. Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Several potential antiviral strategies might be employed in PAMs, including upregulating IFN-induced genes and increasing intracellular zinc ion concentration. And inhibition of the complement system likely attenuated the lung damage during HP-PRRSV infection. Transcriptomic analysis of PAMs in vivo could lead to a better understanding of the HP-PRRSV-host interaction, and to the identification of novel antiviral therapies and genetic components of swine tolerance/susceptibility to HP-PRRS. url: https://www.ncbi.nlm.nih.gov/pubmed/21850204/ doi: nan id: cord-257116-6td3efjw author: Zhou, Yanrong title: Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production date: 2017-08-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus (CoV) of porcine, causes lethal watery diarrhea and severe dehydration in piglets and leads to severe economic losses in the swine industry. Unlike most CoVs that antagonize type I interferon (IFN) production, previous studies showed that TGEV infection induces IFN-I production both in vivo and in vitro. However, the underlying mechanism(s) remain largely unknown. In this study, we found that TGEV infection significantly facilitated IFN-β production as well as activation of the transcription factors IFN regulatory factor 3 (IRF3) and nuclear factor-kappaB (NF-κB) in porcine kidney (PK-15) cells. Screening of TGEV-encoded proteins demonstrated that non-structural protein 14 (nsp14) was the most potent IFN-β inducer and induced IFN-β production mainly by activating NF-κB but not IRF3. Further analysis showed that nsp14 interacted with DDX1, a member of the DExD/H helicase family. Knockdown of DDX1 by specific small interfering RNA (siRNA) significantly decreased nsp14-induced IFN-β production and NF-κB activation. Furthermore, TGEV-induced IFN-β production and IFN-stimulated gene (ISG) expression were decreased in cells transfected with DDX1-specific siRNA, indicating the vital role of DDX1 to TGEV-induced IFN-β responses. In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEV-encoded proteins. url: https://doi.org/10.3389/fimmu.2017.00940 doi: 10.3389/fimmu.2017.00940 id: cord-297712-yy4g5npi author: Zhu, Xinyu title: Porcine deltacoronavirus nsp5 inhibits interferon-β production through the cleavage of NEMO date: 2016-12-13 words: 3284.0 sentences: 190.0 pages: flesch: 57.0 cache: ./cache/cord-297712-yy4g5npi.txt txt: ./txt/cord-297712-yy4g5npi.txt summary: Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-β production by targeting the NF-κB essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV. A study published by our lab also demonstrated that nsp5, the 3C-like protease of porcine epidemic diarrhea virus (PEDV), which is classified into the Alphacoronavirus family, antagonizes IFN-β production by cleavage of NEMO . In this study, we reveal that nsp5 of PDCoV antagonizes the type I IFN signaling pathway through the cleavage of NEMO, a critical constituent of the IKK complex, thus representing a newly identified mechanism by which PDCoV evades the innate immune response. In contrast, TBK1induced activation of the IFN-β promoter was not affected by nsp5 (Fig. 3A) , suggesting that PDCoV nsp5 inhibits RIG-I/MDA5 signaling by targeting NEMO or other upstream proteins. abstract: Porcine deltacoronavirus (PDCoV) causes acute enteric disease and mortality in seronegative neonatal piglets. Previously we have demonstrated that PDCoV infection suppresses the production of interferon-beta (IFN-β), while the detailed mechanisms are poorly understood. Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-β production by targeting the NF-κB essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV. The PDCoV nsp5 cleavage site in the NEMO protein was identified as glutamine 231, and was identical to the porcine epidemic diarrhea virus nsp5 cleavage site, revealing the likelihood of a common target in NEMO for coronaviruses. Furthermore, this cleavage impaired the ability of NEMO to activate the IFN response and downstream signaling. Taken together, our findings reveal PDCoV nsp5 to be a newly identified IFN antagonist and enhance the understanding of immune evasion by deltacoronaviruses. url: https://www.sciencedirect.com/science/article/pii/S0042682216303786 doi: 10.1016/j.virol.2016.12.005 id: cord-300648-ixiam7qr author: Zhu, Xun title: IFITM3‐containing exosome as a novel mediator for anti‐viral response in dengue virus infection date: 2014-08-30 words: 8229.0 sentences: 367.0 pages: flesch: 47.0 cache: ./cache/cord-300648-ixiam7qr.txt txt: ./txt/cord-300648-ixiam7qr.txt summary: At 24 h post infection when the infected cells were examined by real-time RT-PCR assay, strikingly, DENV-2 infection was suppressed potently by the IFITM3-containing exosomes in a dose-dependent manner in parental HeLa cells (Fig. 4A ) or in HeLa cells with endogenous IFITM3 knocked down (Fig. 4C) , and the copy number of DENV-2 viral RNA was reduced in the culture supernatant ( Fig. 4B and D), indicating that the observed antiviral effect was mediated by the exosome-transferred IFITM3. To verify that the enhanced antiviral effects caused by IFITM3-exosome transfer was a result of IFITM3 action rather than a stimulated paracrine IFNs response, the concentration of human IFN-α/β in culture supernatant of HeLa cells or HeLa-siIFITM3 cells treated with IFITM3laden exosomes was measured with ELISA by using Sendai virus (SeV; 100 HAU ml −1 ) as a positive stimulus control. abstract: Interferon‐inducible transmembrane proteins 1, 2 and 3 (IFITM1, IFITM2 and IFITM3) have recently been identified as potent antiviral effectors that function to suppress the entry of a broad range of enveloped viruses and modulate cellular tropism independent of viral receptor expression. However, the antiviral effect and mechanisms of IFITMs in response to viral infections remain incompletely understood and characterized. In this work, we focused our investigation on the function of the extracellular IFITM3 protein. In cell models of DENV‐2 infection, we found that IFITM3 contributed to both the baseline and interferon‐induced inhibition of DENV entry. Most importantly, our study for the first time demonstrated the presence of IFITM‐containing exosome in the extracellular environment, and identified an ability of cellular exosome to intercellularly deliver IFITM3 and thus transmit its antiviral effect from infected to non‐infected cells. Thus, our findings provide new insights in the basic mechanisms underlying the actions of IFITM3, which might lead to future development of exosome‐mediated anti‐viral strategies using IFITM3 as a therapeutic agent. Conceivably, variations in the basal and inducible levels of IFITMs, as well as in intracellular and extracellular levels of IFITMs, might predict the severity of dengue virus infections among individuals or across species. url: https://www.ncbi.nlm.nih.gov/pubmed/25131332/ doi: 10.1111/cmi.12339 id: cord-003239-nph2ezii author: Zhu, Zixiang title: Early Growth Response Gene-1 Suppresses Foot-and-Mouth Disease Virus Replication by Enhancing Type I Interferon Pathway Signal Transduction date: 2018-09-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Early growth response gene-1 (EGR1) is a multifunctional transcription factor that is implicated in viral infection. In this study, we observed that foot-and-mouth disease virus (FMDV) infection significantly triggered EGR1 expression. Overexpression of EGR1 suppressed FMDV replication in porcine cells, and knockdown of EGR1 considerably promoted FMDV replication. A previously reported FMDV mutant virus (with two amino acids mutations in SAP domain) that displays a strong type I interferon (IFN) induction activity was used in this study. We found that SAP mutant FMDV infection induced a higher expression of EGR1 than wildtype FMDV infection, and also triggered higher IFN-β and IFN-stimulated genes (ISGs) expression than wildtype FMDV infection. This implied a link between EGR1 and type I IFN signaling. Further study showed that overexpression of EGR1 resulted in Sendai virus (SeV)-induced IFN-stimulated response element (ISRE) and NF-κB promoter activation. In addition, the SeV-induced ISGs expression was impaired in EGR1 knockdown cells. EGR1 upregulation promoted type I IFN signaling activation and suppressed FMDV and Seneca Valley virus replication. Suppression of the transcriptional activity of EGR1 did not affect its antiviral effect against FMDV. This study reveals a new mechanism evolved by EGR1 to enhance type I IFN signaling and suppress FMDV replication. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170816/ doi: 10.3389/fmicb.2018.02326 id: cord-007696-83v9yfa6 author: Zisman, David A. title: Pulmonary Fibrosis date: 2005 words: 13991.0 sentences: 691.0 pages: flesch: 40.0 cache: ./cache/cord-007696-83v9yfa6.txt txt: ./txt/cord-007696-83v9yfa6.txt summary: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease limited to the lungs and associated with the histologic appearance of usual interstitial pneumonia (UIP) on surgical lung biopsy. Factors that predict poor outcome include older age, male gender, severe dyspnea, history of cigarette smoking, severe loss of lung function, appearance and severity of fibrosis on radiological studies, lack of response to therapy, and prominent fibroblastic foci on histopathologic evaluation. With greater comprehension of the clinical relevance of the different histopathological subgroups that make up the idiopathic interstitial pneumonias, the term idiopathic pulmonary fibrosis (IPF) is now reserved to patients with idiopathic usual interstitial pneumonia (UIP) on surgical lung biopsy. Tang In a recent study, human T-lymphtropic virus type I (HTVL-I) positive IPF patients had more affected lung parenchyma, demonstrated traction bronchiectasis with honeycomb change, and exhibited increased levels of specific cytokines that correlated with activated T-cells in the bronchoalveolar lavage fluid (BALF). abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease limited to the lungs and associated with the histologic appearance of usual interstitial pneumonia (UIP) on surgical lung biopsy. The estimated prevalence in the United States is between 35,000 and 55,000 cases, and evidence suggests that the prevalence is increasing for IPF. Risk factors associated with pulmonary fibrosis include smoking, environmental exposures, gastroesophageal reflux disease, commonly prescribed drugs, diabetes mellitus, infectious agents, and genetic factors. The diagnosis requires a careful history and physical examination, characteristic physiological and radiological studies, and, in some cases, a surgical lung biopsy. The natural history of IPF is not known, but evidence supports the concept of a continuum of idiopathic interstitial pneumonias that may overlap in time. Most patients with IPF succumb to respiratory failure, cardiovascular disease, lung cancer, pulmonary embolism, infection, and other health problems. The median survival time for patients with IPF is less than 3 yr. Factors that predict poor outcome include older age, male gender, severe dyspnea, history of cigarette smoking, severe loss of lung function, appearance and severity of fibrosis on radiological studies, lack of response to therapy, and prominent fibroblastic foci on histopathologic evaluation. Conventional therapy (corticosteroids, azathioprine, cyclophosphamide) provides only marginal benefit. Lung transplantation should be considered for patients with IPF refractory to medical therapy. In light of the poor prognosis and lack of response to available anti-inflammatory therapy, alternative approaches to therapy are being pursued. Emerging strategies to treat patients with IPF include agents that inhibit epithelial injury or enhance repair, anticytokine approaches, agents that inhibit fibroblast proliferation or induce fibroblast apoptosis, and other novel approaches. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120641/ doi: 10.1385/1-59259-940-0:003 id: cord-260729-b12v3c8c author: de Lang, Anna title: Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques date: 2007-08-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS. url: https://www.ncbi.nlm.nih.gov/pubmed/17696609/ doi: 10.1371/journal.ppat.0030112 id: cord-000083-3p81yr4n author: nan title: Poster Exhibition date: 2009-01-31 words: 112815.0 sentences: 7542.0 pages: flesch: 56.0 cache: ./cache/cord-000083-3p81yr4n.txt txt: ./txt/cord-000083-3p81yr4n.txt summary: R. China Background: The objective of this study was to evaluate the early virologic response for prediction of achievement of HBeAg seroconversion and hepatitis B virus (HBV) DNA negativity after two years of lamivudine treatment in chronic hepatitis B (CHB) patients. Methods: A total of 620 patients who tested positive for hepatitis B surface antigen and were referred to Chiba University Hospital between February 1985 and March 2008 were included in the study, and their following characteristics were analyzed: age, gender, the status of HBeAg, ALT, HBV-DNA level, and PLT. Methods: A total of 60 patients with chronic hepatitis B, 32 (53.3%) were HBeAg positive (group A) while 28(46.7%) were HBeAg negative (group B) were included in this study after meeting the following criteria: age 18 to 60 years, HBsAg positive for more than 6 months, serum HBV-DNA was >5 log(10) copies/mL and ALT more than two times the upper normal limit. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712310/ doi: 10.1007/s12072-009-9123-4 id: cord-004675-n8mlxe7p author: nan title: 2019 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date: 2019-02-26 words: 86427.0 sentences: 5050.0 pages: flesch: 46.0 cache: ./cache/cord-004675-n8mlxe7p.txt txt: ./txt/cord-004675-n8mlxe7p.txt summary: However, the mean infusion rate per site was similar between patients aged <18 years ( XMEN disease (X-linked Immunodeficency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a primary immune deficiency caused by mutations in MAGT1 and characterized by chronic infection with Epstein-Barr virus (EBV), EBV-driven lymphoma, CD4 T-cell lymphopenia, and dysgammaglobulinemia. We present the case of a 1-year old Hispanic infant with a pathogenic variant in MAGT1 gene that clinically manifested with early Pneumocystis jirovecii and cytomegalovirus (CMV) interstitial pneumonia, and EBV chronic infection with good response to intravenous immunoglobulins supplementation without hematopoietic stem cell transplantation or gene therapy. Chief, Laboratory of Clinical Immunology and Microbiology, IDGS, DIR, NIAID, NIH, Bethesda, MD, USA Hypomorphic Recombination Activating Gene 1 (RAG1) mutations result in residual T-and B-cell development in both humans and mice and have been found in patients presenting with delayed-onset combined immune deficiency with granulomas and/or autoimmunity (CID-G/AI). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086569/ doi: 10.1007/s10875-019-00597-5 id: cord-005953-5z89yeb6 author: nan title: Abstracts des 114. Internistenkongresses 2008 date: 2008 words: 16135.0 sentences: 1522.0 pages: flesch: 49.0 cache: ./cache/cord-005953-5z89yeb6.txt txt: ./txt/cord-005953-5z89yeb6.txt summary: Die anderen beiden Gruppen zeigten zwar in Hinblick auf die Wandstärken einen positiven Effekt, hinsichtlich der Herzfunktion konnten sie jedoch bei bereits deutlich erniedrigten Funktionswerten zum Baseline-Zeitpunkt lediglich stabilisiert werden (Reduktion der Wandstärke nach 3 Jahren ERT: Gruppe wenig Fibrose= 10 mm; Gruppe viel Fibrose= 12 mm) Schlussfolgerung: Die Enzymersatztherapie ist eine effektive Langzeitbehandlung bei Patienten mit Fabry Kardiomyopathie. Der Einfluss der sauren Sphingomyelinase auf die Expression von Matrix-Metalloproteinase-1 in intestinalen Epithelzellen und Fibroblasten Background: The calcineurin (Cn)/NF-AT signaling cascade takes a crucial role during T-cell activation and the development of myocardial hypertrophy. Effective and safe reduction of blood pressue by the combination of amlodipine 5/valsartan 160 mg in patients with hypertension and metabolic risk factors not controlled by amlodipine 5 mg or felodipine 5 mga subanalysis of the express-m trial Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia and frequently occurs in patients with coronary heart disease. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096012/ doi: 10.1007/s00063-008-1026-y id: cord-006444-eq56zhtd author: nan title: Abstracts of oral presentations and posters date: 1993 words: 40668.0 sentences: 2121.0 pages: flesch: 53.0 cache: ./cache/cord-006444-eq56zhtd.txt txt: ./txt/cord-006444-eq56zhtd.txt summary: The results from ongoing preclinical studies continue to confirm the broad spectrum of biological activities possessed by rhiL-1 1 in vitro and suggest this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation. We performed a phase H trial to assess the ability of G-CSF -mobilized PBPC to rapidly and completely restore hemopeiesis after high dose chemotherapy in the absence of bone marrow infusions, with selection for PBPC-only infusions based on yield of granulocyte -macrophage colony -forming cells (GM-CFC) after G-CSF treatment. Our approach for high-dose (HD) chemotherapy is to first treat patients eligible for dose intensification with a standard dose chemotherapy (VIP: VP26 = etoposide: 500 mg/m 2, ifosfamide: 4 g/m 2, cis-platinum: 50 mg/m 2) followed by the application of colony stimulating factors (G-CSF, GM-CSF or IL-3 + GM-CSF) in order to combine a regimen with broad anti-tumor activity with the recruitment of peripheral blood progenitor cells (PBPCs). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101830/ doi: 10.1007/bf01695978 id: cord-006828-i88on326 author: nan title: Abstracts DGRh-Kongress 2013 date: 2013-09-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103148/ doi: 10.1007/s00393-013-1255-1 id: cord-007890-bie1veti author: nan title: ECC-4 Abstracts date: 2002-04-16 words: 85992.0 sentences: 5665.0 pages: flesch: 50.0 cache: ./cache/cord-007890-bie1veti.txt txt: ./txt/cord-007890-bie1veti.txt summary: Effects of Interferon alpha plus ribavirine therapy on frequencies of HCV, HIV and CMV specific CD4-T-cell responses in peripheral blood of HIV/HCV coinfected patients after 6 months of treatment SoA9.5 Methods: Two groups of patients with chronic HCV infection were studied: 26 HIV coinfected progressors with antiretroviral therapy and 13 HIV-negative controls. In order to assess the local temporal trend of antibiotic sensitivity of the most common urinary tract bacterial pathogen, all urine-cultured Escherichia coli isolates were reviewed as to susceptibility profile, and specimen source (community-versus hospital-acquired infection). Methods: A total of 87 penicillin resistant clinical strains isolated from patients at Hacettepe Children''s Hospital, Ankara, Turkey between 1999 and 2001 were tested for their in vitro susceptibility to various antibiotics that are commonly used in the treatment of respiratory tract infections. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126403/ doi: 10.1016/s0924-8579(02)00033-x id: cord-009567-osstpum6 author: nan title: Abstracts Oral date: 2008-04-23 words: 131214.0 sentences: 7728.0 pages: flesch: 53.0 cache: ./cache/cord-009567-osstpum6.txt txt: ./txt/cord-009567-osstpum6.txt summary: Introduction: Previously, it has been demonstrated that FOXP3, a gene required for the development and function of regulatory T cells, was highly expressed in the graft during cardiac rejection, suggesting infiltration of regulatory T cells in the transplanted organ during an allogeneic response. Efficacy and safety parameters assessed at follow-up included: acute rejection; patient and graft survival; renal function, vital signs, basic lab results and immunosuppressive regimen for the patients 10 years after completion of the original study. We analyzed, for the first time, the expression of TLR4 in PBMC from kidney recipients with contrasted situations: operational tolerance and chronic immune-mediated rejection (Banff 2005), compared to patients with normal histology and stable graft function, non transplant patients with renal failure and healthy volunteers. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159651/ doi: 10.1111/j.1600-6143.2008.02254.x id: cord-015021-pol2qm74 author: nan title: Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date: 1994 words: 162327.0 sentences: 9379.0 pages: flesch: 50.0 cache: ./cache/cord-015021-pol2qm74.txt txt: ./txt/cord-015021-pol2qm74.txt summary: It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095072/ doi: 10.1007/bf02258437 id: cord-015147-h0o0yqv8 author: nan title: Oral Communications and Posters date: 2014-09-12 words: 73711.0 sentences: 3862.0 pages: flesch: 43.0 cache: ./cache/cord-015147-h0o0yqv8.txt txt: ./txt/cord-015147-h0o0yqv8.txt summary: Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095932/ doi: 10.1007/bf03353884 id: cord-017184-1ewi3dka author: nan title: Primary Immunodeficiencies date: 2008 words: 44492.0 sentences: 2035.0 pages: flesch: 45.0 cache: ./cache/cord-017184-1ewi3dka.txt txt: ./txt/cord-017184-1ewi3dka.txt summary: In this disease, microorganism phagocytosis by polymorphonuclear (PMN) leukocytes appears annulled, and the patient is subject to severe infections supported by capsular bacteria: the deficiency, described in association with severe and recurrent infantile infections [175, 485, 487] , depends on the lack of mannose-binding lectin (MBL) [487] , its Primary Immunodeficiencies a possible atopy dependence on IgA underproduction rather than on IgE hyperproduction ( Fig. 4.1 ): in children with levels of IgA at the minimum normal level, and followed from birth until the age of 18-23 months, a greater severity of atopic manifestations and an increased cumulative incidence of asthma, AD and otitis media with effusion (OME) were observed compared to controls. abstract: Primary immunodeficiencies (PIDs), once considered to be very rare, are now increasingly recognized because of growing knowledge in the immunological field and the availability of more sophisticated diagnostic techniques and therapeutic modalities [161]. However in a database of >120,000 inpatients of a general hospital for conditions suggestive of ID 59 patients were tested, and an undiagnosed PID was found in 17 (29%) of the subjects tested [107]. The publication of the first case of agammaglobulinemia by Bruton in 1952 [60] demonstrated that the PID diagnosis is first done in the laboratory. However, PIDs require specialized immunological centers for diagnosis and management [33]. A large body of epidemiological evidence supports the hypothesis of the existence of a close etiopathogenetic relation between PID and atopy [73]. In particular, an elevated frequency of asthma, food allergy (FA), atopic dermatitis and enteric pathologies can be found in various PIDs. In addition we will discuss another subject that is certainly of interest: the pseudo-immunodepressed child with recurrent respiratory infections (RRIs), an event that often requires medical intervention and that very often leads to the suspicion that it involves antibody deficiencies [149]. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121684/ doi: 10.1007/978-3-540-33395-1_22 id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 words: 188640.0 sentences: 9313.0 pages: flesch: 45.0 cache: ./cache/cord-022888-dnsdg04n.txt txt: ./txt/cord-022888-dnsdg04n.txt summary: Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. abstract: No Abtract url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163517/ doi: 10.1002/eji.200990224 id: cord-023017-k6edtg58 author: nan title: AASLD Abstracts (pp. 282A–382A) date: 2006-02-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165819/ doi: 10.1002/hep.1840380505 id: cord-023033-tgt69ir6 author: nan title: Poster Session (pp. 78A–178A) date: 2006-02-10 words: 16102.0 sentences: 855.0 pages: flesch: 45.0 cache: ./cache/cord-023033-tgt69ir6.txt txt: ./txt/cord-023033-tgt69ir6.txt summary: Methods: We performed a retrospective analysis comparing outcomes, and the incidence, timing, and severity of histologic recurrence of HCV following transplantation in patients who underwent living donor liver transplant compared to recipients of cadaveric organs. Local liver immune responses are thought to play a major role in chronic autoimmune diseases directed at biliary epithelium.Using the apical sodium dependent bile acid transporter (ASBT) promoter to drive biliary epithelial cell -specific expression of a membrane form of ovalbumin (OVA), we have previously developed OVA-BIL transgenic mice. Thus, our AIM was to ascertain whether Kupffer cells express death ligands and contribute to hepatocyte apoptosis and liver fibrosis in the bile duct ligated mouse, an animal model of cholestasis. Control experiments confirmed that Y2 protein inhibited IFNa-induced ISRE-mediated signaling in Huh-T7 cells; relative luciferase activity was reduced from 653 (pH771 IFNP nAb increased HCV core Ag replication by 42% and 23% compared to no treatment (p=O.O1). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165951/ doi: 10.1002/hep.1840380503 id: cord-023143-fcno330z author: nan title: Molecular aspects of viral immunity date: 2004-02-19 words: 43425.0 sentences: 2056.0 pages: flesch: 47.0 cache: ./cache/cord-023143-fcno330z.txt txt: ./txt/cord-023143-fcno330z.txt summary: Based on a variety of experimental evidence, it is clear that demyelination induced in SJUJ mice by infection with the BeAn strain of TMEV is a Thl-mediated event: (a) disease induction is suppressed in T cell-deprived mice and by in vivo treatment with anti-I-A and anti-CD4 antibodies; (b) disease susceptibility correlates temporally with the development of TMEV-specific, MHC-class Il-restricted DTH responses and with a predominance of anti-viral lgG2a antibody; (c) activated (Le., lL-2RC) T cells infiltrating the CNS are exclusively of the CD4+ phenotype, and (d) proinflammatory cytokines (IFNq and TNF-p) are predominantly produced in the CNS. These results have important implications for a possible viral trigger in MS as they indicate that chronic demyelination in TMEV-infected mice is initiated in the absence of demonstrable neuroantigen-specific autoimmune responses and are consistent with a model wherein early myelin damage is mediated via primarily by mononuclear phagocytes recruited to the CNS and activated by pro-inflammatory cytokines produced by TMEV-specific Thl cells. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167094/ doi: 10.1002/jcb.240591009 id: cord-023306-3gdfo6vd author: nan title: TSANZ Oral Abstracts date: 2010-03-01 words: 23387.0 sentences: 1370.0 pages: flesch: 54.0 cache: ./cache/cord-023306-3gdfo6vd.txt txt: ./txt/cord-023306-3gdfo6vd.txt summary: Conflict of Interest No. Purpose We examined age trends in the distribution of stage at diagnosis in patients presenting with non-small cell lung cancer (NSCLC) at tertiary hospitals. Methods Eleven healthy male subjects, aged 28(8) (SD) years completed separate visits with (a) no restriction and (b) chest wall strapping to reduce FVC by 30 (7) Introduction Glossopharyngeal breathing (GPB) is used by competitive breath-hold divers to increase lung gas content above TLC to improve performance. Our DC culture results showed that both MHC-I and MHC-II expression on DCs from COPD were significantly down regulated compare to healthy controls, which could affect MHC restricted Ag presentation, and lead to a failure to activate responder T cells. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169109/ doi: 10.1111/j.1440-1843.2010.01735.x id: cord-023443-pvz7dll9 author: nan title: Abstracts for the Scandinavian Society for Immunology 35th Annual Meeting and 20th Summer School date: 2004-06-02 words: 16643.0 sentences: 857.0 pages: flesch: 46.0 cache: ./cache/cord-023443-pvz7dll9.txt txt: ./txt/cord-023443-pvz7dll9.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169613/ doi: 10.1111/j.1365-3083.2004.01423.x id: cord-024651-578c9ut5 author: nan title: 2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date: 2020-05-11 words: 84560.0 sentences: 5089.0 pages: flesch: 47.0 cache: ./cache/cord-024651-578c9ut5.txt txt: ./txt/cord-024651-578c9ut5.txt summary: Abstract/Case Report Text Introduction: Mutations in the gene encoding signal transducer and activator of transcription 3 (STAT3) cause autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES) characterized by recurrent skin and sinopulmonary infections, atopic dermatitis, and elevated serum immunoglobulin E (IgE) levels. Objective: The purpose of this study is to increase awareness and improve diagnosis of primary immune deficiency (PID) in the heterogenous group of patients with autoimmune cytopenia (AIC) by identifying clinical characteristics and laboratory biomarkers that distinguish those with underlying PID, disease activity and guide mechanism-based targeted therapy. 7 Chief, Laboratory of Clinical Immunology and Microbiology/National Institute of Allergy and Infectious Diseases, NIAID/National Institutes of Health, NIH Abstract/Case Report Text We have previously used the artificial thymic organoid (ATO) system, based on the 3D aggregation and culture of a delta-like canonical Notch ligand 4-expressing stromal cell line (MS5-Dll4) with CD34+ cells, to study T cell differentiation from CD34+ cells obtained from patients carrying defects that are intrinsic to hematopoietic cells (RAG1-2, AK2, IL2RG) or that affect thymus development (DiGeorge syndrome). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212516/ doi: 10.1007/s10875-020-00764-z id: cord-299754-tgexahwd author: van Tol, Sarah title: The TRIMendous Role of TRIMs in Virus–Host Interactions date: 2017-08-22 words: 18211.0 sentences: 1015.0 pages: flesch: 41.0 cache: ./cache/cord-299754-tgexahwd.txt txt: ./txt/cord-299754-tgexahwd.txt summary: Downstream of the initial pattern recognition, TRIMs also influence the recruitment and interaction of adaptor molecules (stimulator of IFN genes (STING), mitochondrial antiviral signaling protein (MAVS), TGF-β-activated kinase 1(TAK1)/MAP3K7-binding protein (TAB) 2, Myeloid differentiation primary response gene 88 (MyD88), TIR-domain-containing adapterinducing interferon-β (TRIF), NF-κB essential modulator (NEMO), nucleosome assembly protein (NAP-1), and tumor necrosis factor (TNF) receptor-associated factors (TRAF) family memberassociated NF-κB activator (TANK)) and enzymes (TRAF3, TRAF6, TAK1, inhibitor of NF-κB (IκB) kinase (IKK) α,β,ε, TANK binding kinase 1 (TBK1)) to signaling complexes in order to activate transcription factors. Downstream of the initial pattern recognition, TRIMs also influence the recruitment and interaction of adaptor molecules (stimulator of IFN genes (STING), mitochondrial antiviral signaling protein (MAVS), TGF-β-activated kinase 1(TAK1)/MAP3K7-binding protein (TAB) 2, Myeloid differentiation primary response gene 88 (MyD88), TIR-domain-containing adapter-inducing interferon-β (TRIF), NF-κB essential modulator (NEMO), nucleosome assembly protein (NAP-1), and tumor necrosis factor (TNF) receptor-associated factors (TRAF) family member-associated NF-κB activator (TANK)) and enzymes (TRAF3, TRAF6, TAK1, inhibitor of NF-κB (IκB) kinase (IKK) α,β,ε, TANK binding kinase 1 (TBK1)) to signaling complexes in order to activate transcription factors. abstract: The innate antiviral response is integral in protecting the host against virus infection. Many proteins regulate these signaling pathways including ubiquitin enzymes. The ubiquitin-activating (E1), -conjugating (E2), and -ligating (E3) enzymes work together to link ubiquitin, a small protein, onto other ubiquitin molecules or target proteins to mediate various effector functions. The tripartite motif (TRIM) protein family is a group of E3 ligases implicated in the regulation of a variety of cellular functions including cell cycle progression, autophagy, and innate immunity. Many antiviral signaling pathways, including type-I interferon and NF-κB, are TRIM-regulated, thus influencing the course of infection. Additionally, several TRIMs directly restrict viral replication either through proteasome-mediated degradation of viral proteins or by interfering with different steps of the viral replication cycle. In addition, new studies suggest that TRIMs can exert their effector functions via the synthesis of unconventional polyubiquitin chains, including unanchored (non-covalently attached) polyubiquitin chains. TRIM-conferred viral inhibition has selected for viruses that encode direct and indirect TRIM antagonists. Furthermore, new evidence suggests that the same antagonists encoded by viruses may hijack TRIM proteins to directly promote virus replication. Here, we describe numerous virus–TRIM interactions and novel roles of TRIMs during virus infections. url: https://www.ncbi.nlm.nih.gov/pubmed/28829373/ doi: 10.3390/vaccines5030023 id: cord-028945-p3hhd5ed author: Şahar, Esra Atalay title: Development of a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V and determination of its protective efficacy against acute toxoplasmosis date: 2020-07-10 words: 7383.0 sentences: 433.0 pages: flesch: 55.0 cache: ./cache/cord-028945-p3hhd5ed.txt txt: ./txt/cord-028945-p3hhd5ed.txt summary: Thereafter, we developed a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V and administered to a murine model to determine its immunogenicity and protection efficiency against lethal toxoplasmosis. Hexavalent recombinant protein mixture (+) Montanide ISA 50 V vaccine induced significantly high levels of IgG1 and IgG2a at day 42 compared to the controls groups (P < 0.001, **). Overall, in mice administered with Hexavalent recombinant protein mixture (+) Montanide ISA 50 V, IgG2a and IgG1 levels showed a strong and balanced immune response. Overall, the Th1 part of the immune response elicited by hexavalent recombinant protein mixture (+) Montanide ISA 50 V induced significant levels of CD4 + and CD8 + T lymphocytes secreting IFN-γ and conferred significant protection in Swiss Outbred mice challenged with lethal dose of T. abstract: BACKGROUND: Toxoplasma gondii is an obligate intracellular parasite that can infect almost all warm-blooded animals, avian species and humans. Toxoplasmosis is asymptomatic in healthy individuals, whereas it may lead to death in immune suppressed or deficient patients. A vaccine against T. gondii is required to prevent consequences of the infection. The aim of this study is to generate a multivalent recombinant protein vaccine against T. gondii. METHODS: 49 previously discovered antigenic proteins of T gondii were evaluated by their expression level in E. coli and by comprehensive bioinformatics analyses to determine antigenic epitopes. Based on these analyses, six vaccine candidate proteins were selected to generate a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V. Humoral and cellular immune responses were determined by flow cytometry and ELISA. Vaccinated mice were challenged with T. gondii Ankara strain tachyzoites. RESULTS: In mice vaccinated with hexavalent vaccine, strong total IgG (P < 0.0001) and IgG2a (P < 0.001) responses were induced compared to controls, the ratio of CD4(+) and CD8(+) T lymphocytes secreting IFN-γ increased, and significantly higher extracellular IFN-γ secretion was achieved compared to the controls (P < 0.001). The survival time of the vaccinated mice increased to 8.38 ± 2.13 days which was significantly higher than controls (P < 0.01). CONCLUSIONS: Altogether, these results show that the hexavalent vaccine which is developed for the first time against T. gondii induced strong and balanced Th1 and Th2 immune responses as well as conferred significant protection against challenge with lethal toxoplasmosis in murine model. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348124/ doi: 10.1186/s12879-020-05220-2 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel