Carrel name: journal-viruses-cord Creating study carrel named journal-viruses-cord Initializing database parallel: Warning: Only enough available processes to run 19 jobs in parallel. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf parallel: Warning: or /proc/sys/kernel/pid_max may help. file: cache/cord-000808-pxryt8wn.json key: cord-000808-pxryt8wn authors: Leroy, Eric; Gonzalez, Jean Paul title: Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa date: 2012-09-13 journal: Viruses DOI: 10.3390/v4091592 sha: doc_id: 808 cord_uid: pxryt8wn file: cache/cord-001972-1zisomq5.json key: cord-001972-1zisomq5 authors: Wang, Xue; Tan, Jiying; Biswas, Santanu; Zhao, Jiangqin; Devadas, Krishnakumar; Ye, Zhiping; Hewlett, Indira title: Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells date: 2016-02-02 journal: Viruses DOI: 10.3390/v8020033 sha: doc_id: 1972 cord_uid: 1zisomq5 file: cache/cord-002076-7t4d4vvo.json key: cord-002076-7t4d4vvo authors: Li, Yongfeng; Li, Lian-Feng; Yu, Shaoxiong; Wang, Xiao; Zhang, Lingkai; Yu, Jiahui; Xie, Libao; Li, Weike; Ali, Razim; Qiu, Hua-Ji title: Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology date: 2016-05-06 journal: Viruses DOI: 10.3390/v8050127 sha: doc_id: 2076 cord_uid: 7t4d4vvo file: cache/cord-003407-f5v3hhr8.json key: cord-003407-f5v3hhr8 authors: Hung, Ting-Chun; Jassey, Alagie; Lin, Chien-Ju; Liu, Ching-Hsuan; Lin, Chun-Ching; Yen, Ming-Hong; Lin, Liang-Tzung title: Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection date: 2018-11-27 journal: Viruses DOI: 10.3390/v10120669 sha: doc_id: 3407 cord_uid: f5v3hhr8 file: cache/cord-002590-24o2viv3.json key: cord-002590-24o2viv3 authors: Rahe, Michael C.; Murtaugh, Michael P. title: Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus date: 2017-06-13 journal: Viruses DOI: 10.3390/v9060148 sha: doc_id: 2590 cord_uid: 24o2viv3 file: cache/cord-000804-0hlj6r10.json key: cord-000804-0hlj6r10 authors: Brauburger, Kristina; Hume, Adam J.; Mühlberger, Elke; Olejnik, Judith title: Forty-Five Years of Marburg Virus Research date: 2012-10-01 journal: Viruses DOI: 10.3390/v4101878 sha: doc_id: 804 cord_uid: 0hlj6r10 file: cache/cord-001974-wjf3c7a7.json key: cord-001974-wjf3c7a7 authors: Friis-Nielsen, Jens; Kjartansdóttir, Kristín Rós; Mollerup, Sarah; Asplund, Maria; Mourier, Tobias; Jensen, Randi Holm; Hansen, Thomas Arn; Rey-Iglesia, Alba; Richter, Stine Raith; Nielsen, Ida Broman; Alquezar-Planas, David E.; Olsen, Pernille V. S.; Vinner, Lasse; Fridholm, Helena; Nielsen, Lars Peter; Willerslev, Eske; Sicheritz-Pontén, Thomas; Lund, Ole; Hansen, Anders Johannes; Izarzugaza, Jose M. G.; Brunak, Søren title: Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers date: 2016-02-19 journal: Viruses DOI: 10.3390/v8020053 sha: doc_id: 1974 cord_uid: wjf3c7a7 file: cache/cord-002589-xq3iq8ai.json key: cord-002589-xq3iq8ai authors: Frossard, Jean-Pierre; Grierson, Sylvia; Cheney, Tanya; Steinbach, Falko; Choudhury, Bhudipa; Williamson, Susanna title: UK Pigs at the Time of Slaughter: Investigation into the Correlation of Infection with PRRSV and HEV date: 2017-06-09 journal: Viruses DOI: 10.3390/v9060110 sha: doc_id: 2589 cord_uid: xq3iq8ai file: cache/cord-003284-hjx2d5rq.json key: cord-003284-hjx2d5rq authors: Márquez-Jurado, Silvia; Nogales, Aitor; Ávila-Pérez, Ginés; Iborra, Francisco J.; Martínez-Sobrido, Luis; Almazán, Fernando title: An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo date: 2018-10-07 journal: Viruses DOI: 10.3390/v10100547 sha: doc_id: 3284 cord_uid: hjx2d5rq file: cache/cord-002691-synm1cyw.json key: cord-002691-synm1cyw authors: Hou, Jiun-Nan; Chen, Tien-Huang; Chiang, Yi-Hsuan; Peng, Jing-Yun; Yang, Tsong-Han; Cheng, Chih-Chieh; Sofiyatun, Eny; Chiu, Cheng-Hsun; Chiang-Ni, Chuan; Chen, Wei-June title: PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication date: 2017-09-20 journal: Viruses DOI: 10.3390/v9090262 sha: doc_id: 2691 cord_uid: synm1cyw file: cache/cord-001831-3aonqyub.json key: cord-001831-3aonqyub authors: Royle, Jamie; Dobson, Samuel John; Müller, Marietta; Macdonald, Andrew title: Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals? date: 2015-10-16 journal: Viruses DOI: 10.3390/v7102880 sha: doc_id: 1831 cord_uid: 3aonqyub file: cache/cord-002561-7j43yic1.json key: cord-002561-7j43yic1 authors: Donato, Celeste; Vijaykrishna, Dhanasekaran title: The Broad Host Range and Genetic Diversity of Mammalian and Avian Astroviruses date: 2017-05-10 journal: Viruses DOI: 10.3390/v9050102 sha: doc_id: 2561 cord_uid: 7j43yic1 file: cache/cord-003334-ion97n4b.json key: cord-003334-ion97n4b authors: De Silva Senapathi, Upasama; Abdul-Cader, Mohamed Sarjoon; Amarasinghe, Aruna; van Marle, Guido; Czub, Markus; Gomis, Susantha; Abdul-Careem, Mohamed Faizal title: The In Ovo Delivery of CpG Oligonucleotides Protects against Infectious Bronchitis with the Recruitment of Immune Cells into the Respiratory Tract of Chickens date: 2018-11-15 journal: Viruses DOI: 10.3390/v10110635 sha: doc_id: 3334 cord_uid: ion97n4b file: cache/cord-002994-1zjrunzc.json key: cord-002994-1zjrunzc authors: Faye, Martin; Faye, Oumar; Diagne, Moussa Moise; Fall, Gamou; Weidmann, Manfred; Sembene, Mbacke; Sall, Amadou Alpha; Faye, Ousmane title: Full-Genome Characterization and Genetic Evolution of West African Isolates of Bagaza Virus date: 2018-04-13 journal: Viruses DOI: 10.3390/v10040193 sha: doc_id: 2994 cord_uid: 1zjrunzc file: cache/cord-003453-p2buyrcj.json key: cord-003453-p2buyrcj authors: Batista, Mariana N.; Braga, Ana Cláudia S.; Campos, Guilherme Rodrigues Fernandes; Souza, Marcos Michel; de Matos, Renata Prandini Adum; Lopes, Tairine Zara; Candido, Natalia Maria; Lima, Maria Leticia Duarte; Machado, Francielly Cristina; de Andrade, Stephane Tereza Queiroz; Bittar, Cíntia; Nogueira, Maurício L.; Carneiro, Bruno M.; Mariutti, Ricardo B.; Arni, Raghuvir Krishnaswamy; Calmon, Marilia Freitas; Rahal, Paula title: Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus date: 2019-01-11 journal: Viruses DOI: 10.3390/v11010049 sha: doc_id: 3453 cord_uid: p2buyrcj file: cache/cord-002808-84np9brx.json key: cord-002808-84np9brx authors: Campos, Samuel K. title: Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2 date: 2017-12-03 journal: Viruses DOI: 10.3390/v9120370 sha: doc_id: 2808 cord_uid: 84np9brx file: cache/cord-002185-oz7hras7.json key: cord-002185-oz7hras7 authors: Nelson, Elizabeth A.; Barnes, Alyson B.; Wiehle, Ronald D.; Fontenot, Gregory K.; Hoenen, Thomas; White, Judith M. title: Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications date: 2016-08-02 journal: Viruses DOI: 10.3390/v8080206 sha: doc_id: 2185 cord_uid: oz7hras7 file: cache/cord-003130-p2h8p5bm.json key: cord-003130-p2h8p5bm authors: Lindqvist, Richard; Upadhyay, Arunkumar; Överby, Anna K. title: Tick-Borne Flaviviruses and the Type I Interferon Response date: 2018-06-21 journal: Viruses DOI: 10.3390/v10070340 sha: doc_id: 3130 cord_uid: p2h8p5bm file: cache/cord-001887-d6ycc8ci.json key: cord-001887-d6ycc8ci authors: Romero-Brey, Inés; Bartenschlager, Ralf title: Viral Infection at High Magnification: 3D Electron Microscopy Methods to Analyze the Architecture of Infected Cells date: 2015-12-03 journal: Viruses DOI: 10.3390/v7122940 sha: doc_id: 1887 cord_uid: d6ycc8ci file: cache/cord-003516-l1lq8yga.json key: cord-003516-l1lq8yga authors: Zhang, Jing; Kang, June; Dehghan, Shoaleh; Sridhar, Siddharth; Lau, Susanna K. P.; Ou, Junxian; Woo, Patrick C. Y.; Zhang, Qiwei; Seto, Donald title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations date: 2019-01-31 journal: Viruses DOI: 10.3390/v11020129 sha: doc_id: 3516 cord_uid: l1lq8yga file: cache/cord-003646-kjkuet78.json key: cord-003646-kjkuet78 authors: López-Camacho, César; Chan Kim, Young; Blight, Joshua; Lazaro Moreli, Marcos; Montoya-Diaz, Eduardo; T Huiskonen, Juha; Mareike Kümmerer, Beate; Reyes-Sandoval, Arturo title: Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus date: 2019-04-03 journal: Viruses DOI: 10.3390/v11040322 sha: doc_id: 3646 cord_uid: kjkuet78 file: cache/cord-003761-ikni2acz.json key: cord-003761-ikni2acz authors: Li, Zengbin; Zou, Zixiao; Jiang, Zeju; Huang, Xiaotian; Liu, Qiong title: Biological Function and Application of Picornaviral 2B Protein: A New Target for Antiviral Drug Development date: 2019-06-04 journal: Viruses DOI: 10.3390/v11060510 sha: doc_id: 3761 cord_uid: ikni2acz file: cache/cord-003586-afnto2tz.json key: cord-003586-afnto2tz authors: Baillet, Nicolas; Krieger, Sophie; Journeaux, Alexandra; Caro, Valérie; Tangy, Frédéric; Vidalain, Pierre-Olivier; Baize, Sylvain title: Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses date: 2019-03-23 journal: Viruses DOI: 10.3390/v11030293 sha: doc_id: 3586 cord_uid: afnto2tz file: cache/cord-003775-1axsebya.json key: cord-003775-1axsebya authors: Lelli, Davide; Lavazza, Antonio; Prosperi, Alice; Sozzi, Enrica; Faccin, Francesca; Baioni, Laura; Trogu, Tiziana; Cavallari, Gian Luca; Mauri, Matteo; Gibellini, Anna Maria; Chiapponi, Chiara; Moreno, Ana title: Hypsugopoxvirus: A Novel Poxvirus Isolated from Hypsugo savii in Italy date: 2019-06-19 journal: Viruses DOI: 10.3390/v11060568 sha: doc_id: 3775 cord_uid: 1axsebya file: cache/cord-003865-24lz9tf1.json key: cord-003865-24lz9tf1 authors: Zhou, Hongzhuan; Su, Xia; Lin, Lulu; Zhang, Jin; Qi, Qi; Guo, Fangfang; Xu, Fuzhou; Yang, Bing title: Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells date: 2019-08-13 journal: Viruses DOI: 10.3390/v11080742 sha: doc_id: 3865 cord_uid: 24lz9tf1 file: cache/cord-003859-k8wfyj9b.json key: cord-003859-k8wfyj9b authors: Paweska, Janusz T.; Moolla, Naazneen; Storm, Nadia; Msimang, Veerle; Conteh, Ousman; Weyer, Jacqueline; van Vuren, Petrus Jansen title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera date: 2019-07-24 journal: Viruses DOI: 10.3390/v11080678 sha: doc_id: 3859 cord_uid: k8wfyj9b file: cache/cord-003807-e2txo10z.json key: cord-003807-e2txo10z authors: Ke, Fei; Wang, Zi-Hao; Ming, Cheng-Yue; Zhang, Qi-Ya title: Ranaviruses Bind Cells from Different Species through Interaction with Heparan Sulfate date: 2019-06-29 journal: Viruses DOI: 10.3390/v11070593 sha: doc_id: 3807 cord_uid: e2txo10z file: cache/cord-004020-qtwcbn7m.json key: cord-004020-qtwcbn7m authors: Gao, Yaning; Tai, Wanbo; Wang, Ning; Li, Xiang; Jiang, Shibo; Debnath, Asim K.; Du, Lanying; Chen, Shizhong title: Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors date: 2019-11-02 journal: Viruses DOI: 10.3390/v11111019 sha: doc_id: 4020 cord_uid: qtwcbn7m file: cache/cord-003772-1345qct4.json key: cord-003772-1345qct4 authors: Kummer, Susann; Avinoam, Ori; Kräusslich, Hans-Georg title: IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells date: 2019-06-12 journal: Viruses DOI: 10.3390/v11060548 sha: doc_id: 3772 cord_uid: 1345qct4 file: cache/cord-003961-gs75ebo4.json key: cord-003961-gs75ebo4 authors: Yin, Xin; Feng, Zongdi title: Hepatitis E Virus Entry date: 2019-09-20 journal: Viruses DOI: 10.3390/v11100883 sha: doc_id: 3961 cord_uid: gs75ebo4 file: cache/cord-003697-vmmlxr0o.json key: cord-003697-vmmlxr0o authors: Zhu, Yang; Ma, Yuanmei; Lu, Mijia; Zhang, Yu; Li, Anzhong; Liang, Xueya; Li, Jianrong title: Efficient Production of Human Norovirus-Specific IgY in Egg Yolks by Vaccination of Hens with a Recombinant Vesicular Stomatitis Virus Expressing VP1 Protein date: 2019-05-16 journal: Viruses DOI: 10.3390/v11050444 sha: doc_id: 3697 cord_uid: vmmlxr0o file: cache/cord-003962-lg6gvgwt.json key: cord-003962-lg6gvgwt authors: Zhou, Shaochuan; Ge, Xinna; Kong, Can; Liu, Teng; Liu, Aijing; Gao, Peng; Song, Jiangwei; Zhou, Lei; Guo, Xin; Han, Jun; Yang, Hanchun title: Characterizing the PRRSV nsp2 Deubiquitinase Reveals Dispensability of Cis-Activity for Replication and a Link of nsp2 to Inflammation Induction date: 2019-09-26 journal: Viruses DOI: 10.3390/v11100896 sha: doc_id: 3962 cord_uid: lg6gvgwt file: cache/cord-003861-qeao4ghg.json key: cord-003861-qeao4ghg authors: Aris-Brosou, Stéphane; Parent, Louis; Ibeh, Neke title: Viral Long-Term Evolutionary Strategies Favor Stability over Proliferation date: 2019-07-24 journal: Viruses DOI: 10.3390/v11080677 sha: doc_id: 3861 cord_uid: qeao4ghg file: cache/cord-003915-kje8lvgl.json key: cord-003915-kje8lvgl authors: Pigeyre, Laetitia; Schatz, Malvina; Ravallec, Marc; Gasmi, Leila; Nègre, Nicolas; Clouet, Cécile; Seveno, Martial; El Koulali, Khadija; Decourcelle, Mathilde; Guerardel, Yann; Cot, Didier; Dupressoir, Thierry; Gosselin-Grenet, Anne-Sophie; Ogliastro, Mylène title: Interaction of a Densovirus with Glycans of the Peritrophic Matrix Mediates Oral Infection of the Lepidopteran Pest Spodoptera frugiperda date: 2019-09-17 journal: Viruses DOI: 10.3390/v11090870 sha: doc_id: 3915 cord_uid: kje8lvgl file: cache/cord-003917-bswndfvk.json key: cord-003917-bswndfvk authors: Lalle, Eleonora; Biava, Mirella; Nicastri, Emanuele; Colavita, Francesca; Di Caro, Antonino; Vairo, Francesco; Lanini, Simone; Castilletti, Concetta; Langer, Martin; Zumla, Alimuddin; Kobinger, Gary; Capobianchi, Maria R.; Ippolito, Giuseppe title: Pulmonary Involvement during the Ebola Virus Disease date: 2019-08-24 journal: Viruses DOI: 10.3390/v11090780 sha: doc_id: 3917 cord_uid: bswndfvk file: cache/cord-004018-33zi29bg.json key: cord-004018-33zi29bg authors: Coombs, Kevin M.; Simon, Philippe F.; McLeish, Nigel J.; Zahedi-Amiri, Ali; Kobasa, Darwyn title: Aptamer Profiling of A549 Cells Infected with Low-Pathogenicity and High-Pathogenicity Influenza Viruses date: 2019-11-05 journal: Viruses DOI: 10.3390/v11111028 sha: doc_id: 4018 cord_uid: 33zi29bg file: cache/cord-004022-cr0zskcw.json key: cord-004022-cr0zskcw authors: Lu, Chien-Yi; Lin, Chen-Sheng; Lai, Hsueh-Chou; Yu, Ya-Wen; Liao, Chih-Yi; Su, Wen-Chi; Ko, Bo-Han; Chang, Young-Sheng; Huang, Su-Hua; Lin, Cheng-Wen title: The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles date: 2019-10-31 journal: Viruses DOI: 10.3390/v11111005 sha: doc_id: 4022 cord_uid: cr0zskcw file: cache/cord-004334-y1fcw1dj.json key: cord-004334-y1fcw1dj authors: Kalodimou, Georgia; Veit, Svenja; Jany, Sylvia; Kalinke, Ulrich; Broder, Christopher C.; Sutter, Gerd; Volz, Asisa 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 journal: Viruses DOI: 10.3390/v12010026 sha: doc_id: 4334 cord_uid: y1fcw1dj file: cache/cord-004335-bw3tziup.json key: cord-004335-bw3tziup authors: Perez-Zsolt, Daniel; Martinez-Picado, Javier; Izquierdo-Useros, Nuria title: When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses date: 2019-12-19 journal: Viruses DOI: 10.3390/v12010008 sha: doc_id: 4335 cord_uid: bw3tziup file: cache/cord-009399-6zpkpdzu.json key: cord-009399-6zpkpdzu authors: Sun, Fang; Xia, Zhiqiang; Han, Yuewen; Gao, Minjun; Wang, Luyao; Wu, Yingliang; Sabatier, Jean-Marc; Miao, Lixia; Cao, Zhijian title: Topology, Antiviral Functional Residues and Mechanism of IFITM1 date: 2020-03-08 journal: Viruses DOI: 10.3390/v12030295 sha: doc_id: 9399 cord_uid: 6zpkpdzu file: cache/cord-004509-jkzqmkz6.json key: cord-004509-jkzqmkz6 authors: Thirion, Laurence; Dubot-Peres, Audrey; Pezzi, Laura; Corcostegui, Iban; Touinssi, Mhammed; de Lamballerie, Xavier; Charrel, Remi N. title: Lyophilized Matrix Containing Ready-to-Use Primers and Probe Solution for Standardization of Real-Time PCR and RT-qPCR Diagnostics in Virology date: 2020-01-30 journal: Viruses DOI: 10.3390/v12020159 sha: doc_id: 4509 cord_uid: jkzqmkz6 file: cache/cord-004337-jtaz1gdp.json key: cord-004337-jtaz1gdp authors: Wu, Fangfang; Zhang, Shengnan; Zhang, Ying; Mo, Ruo; Yan, Feihu; Wang, Hualei; Wong, Gary; Chi, Hang; Wang, Tiecheng; Feng, Na; Gao, Yuwei; Xia, Xianzhu; Zhao, Yongkun; Yang, Songtao title: A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses date: 2020-01-03 journal: Viruses DOI: 10.3390/v12010064 sha: doc_id: 4337 cord_uid: jtaz1gdp file: cache/cord-004507-ezuyjcxs.json key: cord-004507-ezuyjcxs authors: Tomazatos, Alexandru; Marschang, Rachel E.; Maranda, Iulia; Baum, Heike; Bialonski, Alexandra; Spînu, Marina; Lühken, Renke; Schmidt-Chanasit, Jonas; Cadar, Daniel title: Letea Virus: Comparative Genomics and Phylogenetic Analysis of a Novel Reassortant Orbivirus Discovered in Grass Snakes (Natrix natrix) date: 2020-02-21 journal: Viruses DOI: 10.3390/v12020243 sha: doc_id: 4507 cord_uid: ezuyjcxs file: cache/cord-004510-cbutpjre.json key: cord-004510-cbutpjre authors: Seetahal, Janine F. R.; Greenberg, Lauren; Satheshkumar, Panayampalli Subbian; Sanchez-Vazquez, Manuel J.; Legall, George; Singh, Shamjeet; Ramkissoon, Vernie; Schountz, Tony; Munster, Vincent; Oura, Christopher A. L.; Carrington, Christine V. F. title: The Serological Prevalence of Rabies Virus-Neutralizing Antibodies in the Bat Population on the Caribbean Island of Trinidad date: 2020-02-05 journal: Viruses DOI: 10.3390/v12020178 sha: doc_id: 4510 cord_uid: cbutpjre file: cache/cord-004508-ok3px98z.json key: cord-004508-ok3px98z authors: Armando, Federico; Gambini, Matteo; Corradi, Attilio; Giudice, Chiara; Pfankuche, Vanessa Maria; Brogden, Graham; Attig, Friederike; von Köckritz-Blickwede, Maren; Baumgärtner, Wolfgang; Puff, Christina title: Oxidative Stress in Canine Histiocytic Sarcoma Cells Induced by an Infection with Canine Distemper Virus Led to a Dysregulation of HIF-1α Downstream Pathway Resulting in a Reduced Expression of VEGF-B In Vitro date: 2020-02-11 journal: Viruses DOI: 10.3390/v12020200 sha: doc_id: 4508 cord_uid: ok3px98z file: cache/cord-011435-x73foqu7.json key: cord-011435-x73foqu7 authors: Glanz, Anna; Chawla, Karan; Fabry, Stephanie; Subramanian, Gayatri; Garcia, Julie; Jay, Bryanna; Ciricillo, Jacob; Chakravarti, Ritu; Taylor, R. Travis; Chattopadhyay, Saurabh title: High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication date: 2020-04-14 journal: Viruses DOI: 10.3390/v12040442 sha: doc_id: 11435 cord_uid: x73foqu7 file: cache/cord-011436-ud35mf5l.json key: cord-011436-ud35mf5l authors: Li, Yingying; Zhao, Ling; Luo, Zhaochen; Zhang, Yachun; Lv, Lei; Zhao, Jianqing; Sui, Baokun; Huang, Fei; Cui, Min; Fu, Zhen F.; Zhou, Ming title: Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation date: 2020-04-06 journal: Viruses DOI: 10.3390/v12040405 sha: doc_id: 11436 cord_uid: ud35mf5l file: cache/cord-011635-vosu7y6j.json key: cord-011635-vosu7y6j authors: Norlander, Allison E.; Peebles, R. Stokes title: Innate Type 2 Responses to Respiratory Syncytial Virus Infection date: 2020-05-08 journal: Viruses DOI: 10.3390/v12050521 sha: doc_id: 11635 cord_uid: vosu7y6j file: cache/cord-011438-imbpgsub.json key: cord-011438-imbpgsub authors: Zhang, Yun; Xu, Zhichao; Cao, Yongchang title: Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection date: 2020-03-29 journal: Viruses DOI: 10.3390/v12040376 sha: doc_id: 11438 cord_uid: imbpgsub file: cache/cord-013174-whg64w0w.json key: cord-013174-whg64w0w authors: Bhatta, Tarka Raj; Ryt-Hansen, Pia; Nielsen, Jens Peter; Larsen, Lars Erik; Larsen, Inge; Chamings, Anthony; Goecke, Nicole B.; Alexandersen, Soren title: Infection Dynamics of Swine Influenza Virus in a Danish Pig Herd Reveals Recurrent Infections with Different Variants of the H1N2 Swine Influenza A Virus Subtype date: 2020-09-10 journal: Viruses DOI: 10.3390/v12091013 sha: doc_id: 13174 cord_uid: whg64w0w file: cache/cord-012845-so2umdlt.json key: cord-012845-so2umdlt authors: Paczesny, Jan; Richter, Łukasz; Hołyst, Robert title: Recent Progress in the Detection of Bacteria Using Bacteriophages: A Review date: 2020-08-03 journal: Viruses DOI: 10.3390/v12080845 sha: doc_id: 12845 cord_uid: so2umdlt file: cache/cord-012418-6ralcn8p.json key: cord-012418-6ralcn8p authors: Schwanke, Hella; Stempel, Markus; Brinkmann, Melanie M. title: Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression date: 2020-07-07 journal: Viruses DOI: 10.3390/v12070733 sha: doc_id: 12418 cord_uid: 6ralcn8p file: cache/cord-012497-n5pu1yeu.json key: cord-012497-n5pu1yeu authors: Rogers, Meredith C.; Miranda-Katz, Margot; Zhang, Yu; Oury, Tim D.; Uccellini, Melissa B.; García-Sastre, Adolfo; Williams, John V. title: STAT2 Limits Host Species Specificity of Human Metapneumovirus date: 2020-07-04 journal: Viruses DOI: 10.3390/v12070724 sha: doc_id: 12497 cord_uid: n5pu1yeu file: cache/cord-013177-whd0znan.json key: cord-013177-whd0znan authors: Han, Zhenzhi; Xiao, Jinbo; Song, Yang; Hong, Mei; Dai, Guolong; Lu, Huanhuan; Zhang, Man; Liang, Yueling; Yan, Dongmei; Zhu, Shuangli; Xu, Wenbo; Zhang, Yong title: The Husavirus Posa-Like Viruses in China, and a New Group of Picornavirales date: 2020-09-07 journal: Viruses DOI: 10.3390/v12090995 sha: doc_id: 13177 cord_uid: whd0znan file: cache/cord-012909-o6t2srim.json key: cord-012909-o6t2srim authors: Chaudhari, Jayeshbhai; Liew, Chia-Sin; Workman, Aspen M.; Riethoven, Jean-Jack M.; Steffen, David; Sillman, Sarah; Vu, Hiep L. 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Cho, Sungchan title: Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity date: 2018-04-20 journal: Viruses DOI: 10.3390/v10040211 sha: doc_id: 270103 cord_uid: g9a72xf6 file: cache/cord-272459-w14finxf.json key: cord-272459-w14finxf authors: Heaton, Nicholas S.; Randall, Glenn title: Dengue Virus and Autophagy date: 2011-08-04 journal: Viruses DOI: 10.3390/v3081332 sha: doc_id: 272459 cord_uid: w14finxf file: cache/cord-272010-kc0gi3cj.json key: cord-272010-kc0gi3cj authors: Anand, Sai Priya; Chen, Yaozong; Prévost, Jérémie; Gasser, Romain; Beaudoin-Bussières, Guillaume; Abrams, Cameron F.; Pazgier, Marzena; Finzi, Andrés title: Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins date: 2020-09-29 journal: Viruses DOI: 10.3390/v12101104 sha: doc_id: 272010 cord_uid: kc0gi3cj file: cache/cord-272666-3uidpr79.json key: cord-272666-3uidpr79 authors: Doyle, Nicole; Neuman, Benjamin W.; Simpson, Jennifer; 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Wilson, Ian A. title: Structural Biology of Influenza Hemagglutinin: An Amaranthine Adventure date: 2020-09-22 journal: Viruses DOI: 10.3390/v12091053 sha: doc_id: 309635 cord_uid: 1tgovkr7 file: cache/cord-309693-f2htekhz.json key: cord-309693-f2htekhz authors: Yu, Meiling; Wang, Li; Ma, Sunting; Wang, Xiaona; Wang, Yusai; Xiao, Ya; Jiang, Yanping; Qiao, Xinyuan; Tang, Lijie; Xu, Yigang; Li, Yijing title: Immunogenicity of eGFP-Marked Recombinant Lactobacillus casei against Transmissible Gastroenteritis Virus and Porcine Epidemic Diarrhea Virus date: 2017-09-25 journal: Viruses DOI: 10.3390/v9100274 sha: doc_id: 309693 cord_uid: f2htekhz file: cache/cord-310734-6v7oru2l.json key: cord-310734-6v7oru2l authors: Bolatti, Elisa M.; Zorec, Tomaž M.; Montani, María E.; Hošnjak, Lea; Chouhy, Diego; Viarengo, Gastón; Casal, Pablo E.; Barquez, Rubén M.; Poljak, Mario; Giri, Adriana A. title: A Preliminary Study of the Virome of the South American Free-Tailed Bats (Tadarida brasiliensis) and Identification of Two Novel Mammalian Viruses date: 2020-04-09 journal: Viruses DOI: 10.3390/v12040422 sha: doc_id: 310734 cord_uid: 6v7oru2l file: cache/cord-308201-lavcsqov.json key: cord-308201-lavcsqov authors: Desforges, Marc; Le Coupanec, Alain; Dubeau, Philippe; Bourgouin, Andréanne; Lajoie, Louise; Dubé, Mathieu; Talbot, Pierre J. title: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? date: 2019-12-20 journal: Viruses DOI: 10.3390/v12010014 sha: doc_id: 308201 cord_uid: lavcsqov file: cache/cord-309571-a0xu1d56.json key: cord-309571-a0xu1d56 authors: Aboughdir, Maryam; Kirwin, Thomas; Abdul Khader, Ashiq; Wang, Brian title: Prognostic Value of Cardiovascular Biomarkers in COVID-19: A Review date: 2020-05-11 journal: Viruses DOI: 10.3390/v12050527 sha: doc_id: 309571 cord_uid: a0xu1d56 file: cache/cord-311008-b7xjlqg3.json key: cord-311008-b7xjlqg3 authors: Zapatero-Belinchón, Francisco J.; Dietzel, Erik; Dolnik, Olga; Döhner, Katinka; Costa, Rui; Hertel, Barbara; Veselkova, Barbora; Kirui, Jared; Klintworth, Anneke; Manns, Michael P.; Pöhlmann, Stefan; Pietschmann, Thomas; Krey, Thomas; Ciesek, Sandra; Gerold, Gisa; Sodeik, Beate; Becker, Stephan; von Hahn, Thomas title: Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors date: 2019-03-19 journal: Viruses DOI: 10.3390/v11030275 sha: doc_id: 311008 cord_uid: b7xjlqg3 file: cache/cord-310579-tnxokfwu.json key: cord-310579-tnxokfwu authors: Kim, Sung-Jae; Nguyen, Van-Giap; Huynh, Thi-My-Le; Park, Yong-Ho; Park, Bong-Kyun; Chung, Hee-Chun title: Molecular Characterization of Porcine Epidemic Diarrhea Virus and Its New Genetic Classification Based on the Nucleocapsid Gene date: 2020-07-23 journal: Viruses DOI: 10.3390/v12080790 sha: doc_id: 310579 cord_uid: tnxokfwu file: cache/cord-309378-sfr1x0ob.json key: cord-309378-sfr1x0ob authors: Röst, Gergely; Bartha, Ferenc A.; Bogya, Norbert; Boldog, Péter; Dénes, Attila; Ferenci, Tamás; Horváth, Krisztina J.; Juhász, Attila; Nagy, Csilla; Tekeli, Tamás; Vizi, Zsolt; Oroszi, Beatrix title: Early Phase of the COVID-19 Outbreak in Hungary and Post-Lockdown Scenarios date: 2020-06-30 journal: Viruses DOI: 10.3390/v12070708 sha: doc_id: 309378 cord_uid: sfr1x0ob file: cache/cord-311205-3uwiys4a.json key: cord-311205-3uwiys4a authors: Hung, Yu-Fu; Schwarten, Melanie; Hoffmann, Silke; Willbold, Dieter; Sklan, Ella H.; Koenig, Bernd W. title: Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes date: 2015-07-21 journal: Viruses DOI: 10.3390/v7072812 sha: doc_id: 311205 cord_uid: 3uwiys4a file: cache/cord-310255-aixq5mhf.json key: cord-310255-aixq5mhf authors: Charlton, Frank W.; Pearson, Hayley M.; Hover, Samantha; Lippiat, Jon D.; Fontana, Juan; Barr, John N.; Mankouri, Jamel title: Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives date: 2020-08-03 journal: Viruses DOI: 10.3390/v12080844 sha: doc_id: 310255 cord_uid: aixq5mhf file: cache/cord-312001-8p7scli8.json key: cord-312001-8p7scli8 authors: Majzoub, Karim; Wrensch, Florian; Baumert, Thomas F. title: The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans date: 2019-08-16 journal: Viruses DOI: 10.3390/v11080758 sha: doc_id: 312001 cord_uid: 8p7scli8 file: cache/cord-312272-g4n426cm.json key: cord-312272-g4n426cm authors: Matczuk, Anna Karolina; Chodaczek, Grzegorz; Ugorski, Maciej title: Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells date: 2019-08-09 journal: Viruses DOI: 10.3390/v11080735 sha: doc_id: 312272 cord_uid: g4n426cm file: cache/cord-313161-07iwwsfz.json key: cord-313161-07iwwsfz authors: Lundstrom, Kenneth title: Alphavirus-Based Vaccines date: 2014-06-16 journal: Viruses DOI: 10.3390/v6062392 sha: doc_id: 313161 cord_uid: 07iwwsfz file: cache/cord-313312-h607itv2.json key: cord-313312-h607itv2 authors: Mok, Darren Z. L.; Chan, Kuan Rong title: The Effects of Pre-Existing Antibodies on Live-Attenuated Viral Vaccines date: 2020-05-08 journal: Viruses DOI: 10.3390/v12050520 sha: doc_id: 313312 cord_uid: h607itv2 file: cache/cord-314340-ltx4w9zh.json key: cord-314340-ltx4w9zh authors: Zhu, Liqian; Jiang, Xinyi; Fu, Xiaotian; Qi, Yanhua; Zhu, Guoqiang title: The Involvement of Histone H3 Acetylation in Bovine Herpesvirus 1 Replication in MDBK Cells date: 2018-09-27 journal: Viruses DOI: 10.3390/v10100525 sha: doc_id: 314340 cord_uid: ltx4w9zh file: cache/cord-313439-cadyykks.json key: cord-313439-cadyykks authors: Felten, Sandra; Hartmann, Katrin title: Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature date: 2019-11-15 journal: Viruses DOI: 10.3390/v11111068 sha: doc_id: 313439 cord_uid: cadyykks file: cache/cord-314505-7qh8dsew.json key: cord-314505-7qh8dsew authors: Stegelmeier, Ashley A.; van Vloten, Jacob P.; Mould, Robert C.; Klafuric, Elaine M.; Minott, Jessica A.; Wootton, Sarah K.; Bridle, Byram W.; Karimi, Khalil title: Myeloid Cells during Viral Infections and Inflammation date: 2019-02-19 journal: Viruses DOI: 10.3390/v11020168 sha: doc_id: 314505 cord_uid: 7qh8dsew file: cache/cord-317026-9zgc6xrb.json key: cord-317026-9zgc6xrb authors: Zhao, Shan; Smits, Constance; Schuurman, Nancy; Barnum, Samantha; Pusterla, Nicola; van Kuppeveld, Frank; Bosch, Berend-Jan; van Maanen, Kees; Egberink, Herman title: Development and Validation of a S1 Protein-Based ELISA for the Specific Detection of Antibodies against Equine Coronavirus date: 2019-11-30 journal: Viruses DOI: 10.3390/v11121109 sha: doc_id: 317026 cord_uid: 9zgc6xrb file: cache/cord-314891-brgtwxhe.json key: cord-314891-brgtwxhe authors: Fumian, Tulio M.; Tuipulotu, Daniel Enosi; Netzler, Natalie E.; Lun, Jennifer H.; Russo, Alice G.; Yan, Grace J. H.; White, Peter A. title: Potential Therapeutic Agents for Feline Calicivirus Infection date: 2018-08-16 journal: Viruses DOI: 10.3390/v10080433 sha: doc_id: 314891 cord_uid: brgtwxhe file: cache/cord-315164-nidgnvvi.json key: cord-315164-nidgnvvi authors: Medkour, Hacène; Amona, Inestin; Akiana, Jean; Davoust, Bernard; Bitam, Idir; Levasseur, Anthony; Tall, Mamadou Lamine; Diatta, Georges; Sokhna, Cheikh; Hernandez-Aguilar, Raquel Adriana; Barciela, Amanda; Gorsane, Slim; La Scola, Bernard; Raoult, Didier; Fenollar, Florence; Mediannikov, Oleg title: Adenovirus Infections in African Humans and Wild Non-Human Primates: Great Diversity and Cross-Species Transmission date: 2020-06-18 journal: Viruses DOI: 10.3390/v12060657 sha: doc_id: 315164 cord_uid: nidgnvvi file: cache/cord-317496-6o2upns3.json key: cord-317496-6o2upns3 authors: Pascual-Iglesias, Alejandro; Sanchez, Carlos M.; Penzes, Zoltan; Sola, Isabel; Enjuanes, Luis; Zuñiga, Sonia title: Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV)—Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV date: 2019-07-25 journal: Viruses DOI: 10.3390/v11080682 sha: doc_id: 317496 cord_uid: 6o2upns3 file: cache/cord-317587-rrx2r4n2.json key: cord-317587-rrx2r4n2 authors: Fan, Wensheng; Tang, Ning; Dong, Zhihua; Chen, Jiming; Zhang, Wen; Zhao, Changrun; He, Yining; Li, Meng; Wu, Cuilan; Wei, Tianchao; Huang, Teng; Mo, Meilan; Wei, Ping title: Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure date: 2019-09-26 journal: Viruses DOI: 10.3390/v11100898 sha: doc_id: 317587 cord_uid: rrx2r4n2 file: cache/cord-320212-fw51w4nm.json key: cord-320212-fw51w4nm authors: Friedman, Stephanie D.; Snellgrove, Wyatt C.; Genthner, Fred J. title: Genomic Sequences of two Novel Levivirus Single-Stranded RNA Coliphages (Family Leviviridae): Evidence for Recombinationin Environmental Strains date: 2012-09-13 journal: Viruses DOI: 10.3390/v4091548 sha: doc_id: 320212 cord_uid: fw51w4nm file: cache/cord-317715-xtsi663k.json key: cord-317715-xtsi663k authors: Ortiz-Riaño, Emilio; Cheng, Benson Y. 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Gregory; Yu, Kwang H.; Jancovich, James K. title: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date: 2011-10-20 journal: Viruses DOI: 10.3390/v3101959 sha: doc_id: 320015 cord_uid: lbr2q4qh file: cache/cord-320921-eumuid3r.json key: cord-320921-eumuid3r authors: Widagdo, W.; Okba, Nisreen M. A.; Richard, Mathilde; de Meulder, Dennis; Bestebroer, Theo M.; Lexmond, Pascal; Farag, Elmoubasher A. B. A.; Al-Hajri, Mohammed; Stittelaar, Koert J.; de Waal, Leon; van Amerongen, Geert; van den Brand, Judith M. 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Sardi, Silvia; H. Carvalho, Rejane; C. Pacheco, Luis G.; P. d. Almeida, João P.; M. d. A. Belitardo, Emilia M.; S. Pinheiro, Carina; S. Campos, Gúbio; R. G. R. 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Feng, Shuo; Wang, Jing-Han; He, Wen-Rui; Qin, Hua-Yang; Dong, Hong; Li, Lian-Feng; Yu, Shao-Xiong; Li, Yongfeng; Qiu, Hua-Ji title: eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus date: 2015-08-10 journal: Viruses DOI: 10.3390/v7082833 sha: doc_id: 323585 cord_uid: iv2dcpqj file: cache/cord-324617-yok7mh70.json key: cord-324617-yok7mh70 authors: Andreata-Santos, Robert; Alves, Rúbens Prince dos Santos; Pereira, Sara Araujo; Pereira, Lennon Ramos; de Freitas, Carla Longo; Pereira, Samuel Santos; Venceslau-Carvalho, Alexia Adrianne; Castro-Amarante, Maria Fernanda; Favaro, Marianna Teixeira Pinho; Mathias-Santos, Camila; Amorim, Jaime Henrique; Ferreira, Luís Carlos de Souza title: Transcutaneous Administration of Dengue Vaccines date: 2020-05-06 journal: Viruses DOI: 10.3390/v12050514 sha: doc_id: 324617 cord_uid: yok7mh70 file: cache/cord-325574-4zf9qtlh.json key: cord-325574-4zf9qtlh authors: Farag, Elmoubasher; Sikkema, Reina S.; Vinks, Tinka; 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Lv, Maojie; Chen, Jianfei; Shi, Hongyan; Zhang, Sha; Zhang, Xin; Feng, Li title: Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus date: 2014-03-13 journal: Viruses DOI: 10.3390/v6031253 sha: doc_id: 330475 cord_uid: mameyzih file: cache/cord-331094-22366b81.json key: cord-331094-22366b81 authors: Ianevski, Aleksandr; Yao, Rouan; Fenstad, Mona Høysæter; Biza, Svetlana; Zusinaite, Eva; Reisberg, Tuuli; Lysvand, Hilde; Løseth, Kirsti; Landsem, Veslemøy Malm; Malmring, Janne Fossum; Oksenych, Valentyn; Erlandsen, Sten Even; Aas, Per Arne; Hagen, Lars; Pettersen, Caroline H.; Tenson, Tanel; Afset, Jan Egil; Nordbø, Svein Arne; Bjørås, Magnar; Kainov, Denis E. title: Potential Antiviral Options against SARS-CoV-2 Infection date: 2020-06-13 journal: Viruses DOI: 10.3390/v12060642 sha: doc_id: 331094 cord_uid: 22366b81 file: cache/cord-332576-pd62s65y.json key: cord-332576-pd62s65y authors: Lu, Chien-Yi; Hour, Mann-Jen; Wang, Ching-Ying; Huang, Su-Hua; Mu, Wen-Xiang; Chang, Yu-Chun; Lin, Cheng-Wen title: Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus date: 2017-04-10 journal: Viruses DOI: 10.3390/v9040076 sha: doc_id: 332576 cord_uid: pd62s65y file: cache/cord-331414-i0oxm5mr.json key: cord-331414-i0oxm5mr authors: Kautz, Tiffany F.; Jaworski, Elizabeth; Routh, Andrew; Forrester, Naomi L. title: A Low Fidelity Virus Shows Increased Recombination during the Removal of an Alphavirus Reporter Gene date: 2020-06-19 journal: Viruses DOI: 10.3390/v12060660 sha: doc_id: 331414 cord_uid: i0oxm5mr file: cache/cord-332915-4o2dsf56.json key: cord-332915-4o2dsf56 authors: Hong, Seung-Min; An, Se-Hee; Lee, Chung-Young; Song, Chang-Seon; Choi, Kang-Seuk; Kim, Jae-Hong; Kwon, Hyuk-Joon title: Pathobiological and Genomic Characterization of a Cold-Adapted Infectious Bronchitis Virus (BP-caKII) date: 2018-11-19 journal: Viruses DOI: 10.3390/v10110652 sha: doc_id: 332915 cord_uid: 4o2dsf56 file: cache/cord-332165-31tbc31x.json key: cord-332165-31tbc31x authors: Rustmeier, Nils H.; Strebl, Michael; Stehle, Thilo title: The Symmetry of Viral Sialic Acid Binding Sites—Implications for Antiviral Strategies date: 2019-10-14 journal: Viruses DOI: 10.3390/v11100947 sha: doc_id: 332165 cord_uid: 31tbc31x file: cache/cord-334027-xhfmio7k.json key: cord-334027-xhfmio7k authors: Fagre, Anna C.; Kading, Rebekah C. title: Can Bats Serve as Reservoirs for Arboviruses? date: 2019-03-03 journal: Viruses DOI: 10.3390/v11030215 sha: doc_id: 334027 cord_uid: xhfmio7k file: cache/cord-334134-fhie2m3u.json key: cord-334134-fhie2m3u authors: Mazaleuskaya, Liudmila; Veltrop, Rogier; Ikpeze, Nneka; Martin-Garcia, Julio; Navas-Martin, Sonia title: Protective Role of Toll-like Receptor 3-Induced Type I Interferon in Murine Coronavirus Infection of Macrophages date: 2012-05-24 journal: Viruses DOI: 10.3390/v4050901 sha: doc_id: 334134 cord_uid: fhie2m3u file: cache/cord-334560-1j9zmuub.json key: cord-334560-1j9zmuub authors: Hunt, Catherine L.; Lennemann, Nicholas J.; Maury, Wendy title: Filovirus Entry: A Novelty in the Viral Fusion World date: 2012-02-07 journal: Viruses DOI: 10.3390/v4020258 sha: doc_id: 334560 cord_uid: 1j9zmuub file: cache/cord-334855-s0ci3r8w.json key: cord-334855-s0ci3r8w authors: Andersen, Petter I.; Krpina, Klara; Ianevski, Aleksandr; Shtaida, Nastassia; Jo, Eunji; Yang, Jaewon; Koit, Sandra; Tenson, Tanel; Hukkanen, Veijo; Anthonsen, Marit W.; Bjoras, Magnar; Evander, Magnus; Windisch, Marc P.; Zusinaite, Eva; Kainov, Denis E. title: Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine date: 2019-10-18 journal: Viruses DOI: 10.3390/v11100964 sha: doc_id: 334855 cord_uid: s0ci3r8w file: cache/cord-335279-cfv18qn0.json key: cord-335279-cfv18qn0 authors: Paillot, Romain title: Special Issue “Equine Viruses”: Old “Friends” and New Foes? date: 2020-01-29 journal: Viruses DOI: 10.3390/v12020153 sha: doc_id: 335279 cord_uid: cfv18qn0 file: cache/cord-335567-ssnvr6nj.json key: cord-335567-ssnvr6nj authors: Berry, Michael; Gamieldien, Junaid; Fielding, Burtram C. title: Identification of New Respiratory Viruses in the New Millennium date: 2015-03-06 journal: Viruses DOI: 10.3390/v7030996 sha: doc_id: 335567 cord_uid: ssnvr6nj file: cache/cord-335614-qh98622y.json key: cord-335614-qh98622y authors: Xu, Puzhi; Liu, Ping; Zhou, Changming; Shi, Yan; Wu, Qingpeng; Yang, Yitian; Li, Guyue; Hu, Guoliang; Guo, Xiaoquan title: A Multi-Omics Study of Chicken Infected by Nephropathogenic Infectious Bronchitis Virus date: 2019-11-16 journal: Viruses DOI: 10.3390/v11111070 sha: doc_id: 335614 cord_uid: qh98622y file: cache/cord-337339-0vkigjv2.json key: cord-337339-0vkigjv2 authors: Osterrieder, Nikolaus; Bertzbach, Luca D.; Dietert, Kristina; Abdelgawad, Azza; Vladimirova, Daria; Kunec, Dusan; Hoffmann, Donata; Beer, Martin; Gruber, Achim D.; Trimpert, Jakob title: Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters date: 2020-07-20 journal: Viruses DOI: 10.3390/v12070779 sha: doc_id: 337339 cord_uid: 0vkigjv2 file: cache/cord-336536-ie5ok0lz.json key: cord-336536-ie5ok0lz authors: Yeh, Ming Te; Capponi, Sara; Catching, Adam; Bianco, Simone; Andino, Raul title: Mapping Attenuation Determinants in Enterovirus-D68 date: 2020-08-08 journal: Viruses DOI: 10.3390/v12080867 sha: doc_id: 336536 cord_uid: ie5ok0lz file: cache/cord-337707-xbwilp1w.json key: cord-337707-xbwilp1w authors: Kin, Nathalie; Miszczak, Fabien; Lin, Wei; Ar Gouilh, Meriadeg; Vabret, Astrid title: Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes date: 2015-05-07 journal: Viruses DOI: 10.3390/v7052358 sha: doc_id: 337707 cord_uid: xbwilp1w file: cache/cord-338589-1ent68fx.json key: cord-338589-1ent68fx authors: Stoddard, Shana V.; Stoddard, Serena D.; Oelkers, Benjamin K.; Fitts, Kennedi; Whalum, Kellen; Whalum, Kaylah; Hemphill, Alexander D.; Manikonda, Jithin; Martinez, Linda Michelle; Riley, Elizabeth G.; Roof, Caroline M.; Sarwar, Nowreen; Thomas, Doni M.; Ulmer, Emily; Wallace, Felissa E.; Pandey, Pankaj; Roy, Sudeshna title: Optimization Rules for SARS-CoV-2 M(pro) Antivirals: Ensemble Docking and Exploration of the Coronavirus Protease Active Site date: 2020-08-26 journal: Viruses DOI: 10.3390/v12090942 sha: doc_id: 338589 cord_uid: 1ent68fx file: cache/cord-338436-0z828org.json key: cord-338436-0z828org authors: Tzou, Philip L.; Tao, Kaiming; Nouhin, Janin; Rhee, Soo-Yon; Hu, Benjamin D.; Pai, Shruti; Parkin, Neil; Shafer, Robert W. title: Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date: 2020-09-09 journal: Viruses DOI: 10.3390/v12091006 sha: doc_id: 338436 cord_uid: 0z828org file: cache/cord-338811-2bi2edcw.json key: cord-338811-2bi2edcw authors: Lennemann, Nicholas J.; Evans, Azia S.; Coyne, Carolyn B. title: Imaging-Based Reporter Systems to Define CVB-Induced Membrane Remodeling in Living Cells date: 2020-09-25 journal: Viruses DOI: 10.3390/v12101074 sha: doc_id: 338811 cord_uid: 2bi2edcw file: cache/cord-339752-o6atz33c.json key: cord-339752-o6atz33c authors: Xiao, Li; Sakagami, Hiroshi; Miwa, Nobuhiko title: ACE2: The Key Molecule for Understanding the Pathophysiology of Severe and Critical Conditions of COVID-19: Demon or Angel? date: 2020-04-28 journal: Viruses DOI: 10.3390/v12050491 sha: doc_id: 339752 cord_uid: o6atz33c file: cache/cord-341968-uc8i9h0m.json key: cord-341968-uc8i9h0m authors: Izaguirre, Gonzalo title: The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases date: 2019-09-09 journal: Viruses DOI: 10.3390/v11090837 sha: doc_id: 341968 cord_uid: uc8i9h0m file: cache/cord-341138-mxjsp3cm.json key: cord-341138-mxjsp3cm authors: Denner, Joachim title: Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV) date: 2016-12-20 journal: Viruses DOI: 10.3390/v8120336 sha: doc_id: 341138 cord_uid: mxjsp3cm file: cache/cord-338973-73a7uvyz.json key: cord-338973-73a7uvyz authors: Xu, Jiabao; Zhao, Shizhe; Teng, Tieshan; Abdalla, Abualgasim Elgaili; Zhu, Wan; Xie, Longxiang; Wang, Yunlong; Guo, Xiangqian title: Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV date: 2020-02-22 journal: Viruses DOI: 10.3390/v12020244 sha: doc_id: 338973 cord_uid: 73a7uvyz file: cache/cord-342130-eo4le4v3.json key: cord-342130-eo4le4v3 authors: Qin, Pan; Du, En-Zhong; Luo, Wen-Ting; Yang, Yong-Le; Zhang, Yu-Qi; Wang, Bin; Huang, Yao-Wei title: Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy date: 2019-05-18 journal: Viruses DOI: 10.3390/v11050455 sha: doc_id: 342130 cord_uid: eo4le4v3 file: cache/cord-342739-iy9vjpuh.json key: cord-342739-iy9vjpuh authors: Schwartz, David A.; Graham, Ashley L. title: Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections date: 2020-02-10 journal: Viruses DOI: 10.3390/v12020194 sha: doc_id: 342739 cord_uid: iy9vjpuh file: cache/cord-342923-prgorr3d.json key: cord-342923-prgorr3d authors: Li, Zhonghua; Zeng, Wei; Ye, Shiyi; Lv, Jian; Nie, Axiu; Zhang, Bingzhou; Sun, Yumei; Han, Heyou; He, Qigai title: Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication date: 2018-03-13 journal: Viruses DOI: 10.3390/v10030127 sha: doc_id: 342923 cord_uid: prgorr3d file: cache/cord-343690-rafvxgx1.json key: cord-343690-rafvxgx1 authors: Hartmann, Katrin title: Clinical Aspects of Feline Retroviruses: A Review date: 2012-10-31 journal: Viruses DOI: 10.3390/v4112684 sha: doc_id: 343690 cord_uid: rafvxgx1 file: cache/cord-345472-qrddwebe.json key: cord-345472-qrddwebe authors: Sebina, Ismail; Phipps, Simon title: The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis date: 2020-07-27 journal: Viruses DOI: 10.3390/v12080808 sha: doc_id: 345472 cord_uid: qrddwebe file: cache/cord-345651-admlzeu4.json key: cord-345651-admlzeu4 authors: Wang, Gang; Liang, Rui; Liu, Ziwei; Shen, Zhou; Shi, Jiale; Shi, Yuejun; Deng, Feng; Xiao, Shaobo; Fu, Zhen F.; Peng, Guiqing title: The N-Terminal Domain of Spike Protein Is Not the Enteric Tropism Determinant for Transmissible Gastroenteritis Virus in Piglets date: 2019-03-30 journal: Viruses DOI: 10.3390/v11040313 sha: doc_id: 345651 cord_uid: admlzeu4 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-347053-m5m4zgfy.json key: cord-347053-m5m4zgfy authors: Pharo, Elizabeth A.; Williams, Sinéad M.; Boyd, Victoria; Sundaramoorthy, Vinod; Durr, Peter A.; Baker, Michelle L. title: Host–Pathogen Responses to Pandemic Influenza H1N1pdm09 in a Human Respiratory Airway Model date: 2020-06-24 journal: Viruses DOI: 10.3390/v12060679 sha: doc_id: 347053 cord_uid: m5m4zgfy file: cache/cord-347362-e4paw26n.json key: cord-347362-e4paw26n authors: Klein-Richers, Ute; Hartmann, Katrin; Hofmann-Lehmann, Regina; Unterer, Stefan; Bergmann, Michèle; Rieger, Anna; Leutenegger, Christian; Pantchev, Nikola; Balzer, Jörg; Felten, Sandra title: Prevalence of Feline Coronavirus Shedding in German Catteries and Associated Risk Factors date: 2020-09-08 journal: Viruses DOI: 10.3390/v12091000 sha: doc_id: 347362 cord_uid: e4paw26n file: cache/cord-348968-0yoq0geu.json key: cord-348968-0yoq0geu authors: Zhang, Maodong; Huang, Yanyun; Godson, Dale L.; Fernando, Champika; Alexander, Trevor W.; Hill, Janet E. title: Assessment of Metagenomic Sequencing and qPCR for Detection of Influenza D Virus in Bovine Respiratory Tract Samples date: 2020-07-28 journal: Viruses DOI: 10.3390/v12080814 sha: doc_id: 348968 cord_uid: 0yoq0geu file: cache/cord-349011-kxhpdvri.json key: cord-349011-kxhpdvri authors: Grandvaux, Nathalie; McCormick, Craig title: CSV2018: The 2nd Symposium of the Canadian Society for Virology date: 2019-01-18 journal: Viruses DOI: 10.3390/v11010079 sha: doc_id: 349011 cord_uid: kxhpdvri file: cache/cord-349560-8n65rgfz.json key: cord-349560-8n65rgfz authors: Kleines, Michael; Häusler, Martin; Krüttgen, Alexander; Scheithauer, Simone title: WU Polyomavirus (WUPyV): A Recently Detected Virus Causing Respiratory Disease? date: 2009-11-04 journal: Viruses DOI: 10.3390/v1030678 sha: doc_id: 349560 cord_uid: 8n65rgfz file: cache/cord-349117-xfir3m5p.json key: cord-349117-xfir3m5p authors: Hyseni, Inesa; Molesti, Eleonora; Benincasa, Linda; Piu, Pietro; Casa, Elisa; Temperton, Nigel J; Manenti, Alessandro; Montomoli, Emanuele title: Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays date: 2020-09-10 journal: Viruses DOI: 10.3390/v12091011 sha: doc_id: 349117 cord_uid: xfir3m5p file: cache/cord-350964-0jtfc271.json key: cord-350964-0jtfc271 authors: Van Nguyen, Dung; Van Nguyen, Cuong; Bonsall, David; Ngo, Tue Tri; Carrique-Mas, Juan; Pham, Anh Hong; Bryant, Juliet E.; Thwaites, Guy; Baker, Stephen; Woolhouse, Mark; Simmonds, Peter title: Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam date: 2018-02-28 journal: Viruses DOI: 10.3390/v10030102 sha: doc_id: 350964 cord_uid: 0jtfc271 file: cache/cord-351228-hpo8bboi.json key: cord-351228-hpo8bboi authors: Wasilenko, Shawn T.; Montano-Loza, Aldo J.; Mason, Andrew L. title: Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis? date: 2013-01-24 journal: Viruses DOI: 10.3390/v5020423 sha: doc_id: 351228 cord_uid: hpo8bboi file: cache/cord-351365-dc9t3vh3.json key: cord-351365-dc9t3vh3 authors: Todt, Daniel; Walter, Stephanie; Brown, Richard J. P.; Steinmann, Eike title: Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations date: 2016-10-13 journal: Viruses DOI: 10.3390/v8100283 sha: doc_id: 351365 cord_uid: dc9t3vh3 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-351377-xorj8tnz.json key: cord-351377-xorj8tnz authors: Kao, Chi-Fei; Chiou, Hue-Ying; Chang, Yen-Chen; Hsueh, Cheng-Shun; Jeng, Chian-Ren; Tsai, Pei-Shiue; Cheng, Ivan-Chen; Pang, Victor Fei; Chang, Hui-Wen title: The Characterization of Immunoprotection Induced by a cDNA Clone Derived from the Attenuated Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strain date: 2018-10-04 journal: Viruses DOI: 10.3390/v10100543 sha: doc_id: 351377 cord_uid: xorj8tnz file: cache/cord-351760-698voi9y.json key: cord-351760-698voi9y authors: Han, Hui-Ju; Liu, Jian-Wei; Yu, Hao; Yu, Xue-Jie title: Neutralizing Monoclonal Antibodies as Promising Therapeutics against Middle East Respiratory Syndrome Coronavirus Infection date: 2018-11-30 journal: Viruses DOI: 10.3390/v10120680 sha: doc_id: 351760 cord_uid: 698voi9y file: cache/cord-351955-9l4786lb.json key: cord-351955-9l4786lb authors: Pedersen, Niels C.; Liu, Hongwei; Dodd, Kimberly A.; Pesavento, Patricia A. title: Significance of Coronavirus Mutants in Feces and Diseased Tissues of Cats Suffering from Feline Infectious Peritonitis date: 2009-08-26 journal: Viruses DOI: 10.3390/v1020166 sha: doc_id: 351955 cord_uid: 9l4786lb file: cache/cord-352007-3djwbivp.json key: cord-352007-3djwbivp authors: Xiang, Qi; Wan, Pin; Yang, Ge; Huang, Siyu; Qin, Mengying; Yang, Hua; Luo, Zhen; Wu, Kailang; Wu, Jianguo title: Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication date: 2020-07-14 journal: Viruses DOI: 10.3390/v12070756 sha: doc_id: 352007 cord_uid: 3djwbivp file: cache/cord-352527-eeyqh9nc.json key: cord-352527-eeyqh9nc authors: Zhou, Yusen; Yang, Yang; Huang, Jingwei; Jiang, Shibo; Du, Lanying title: Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain date: 2019-01-14 journal: Viruses DOI: 10.3390/v11010060 sha: doc_id: 352527 cord_uid: eeyqh9nc file: cache/cord-353365-ujz5nkk3.json key: cord-353365-ujz5nkk3 authors: Pirnay, Jean-Paul; Selhorst, Philippe; Cochez, Christel; Petrillo, Mauro; Claes, Vincent; Van der Beken, Yolien; Verbeken, Gilbert; Degueldre, Julie; T’Sas, France; Van den Eede, Guy; Weuts, Wouter; Smets, Cedric; Mertens, Jan; Geeraerts, Philippe; Ariën, Kevin K.; Neirinckx, Pierre; Soentjens, Patrick title: Study of a SARS-CoV-2 Outbreak in a Belgian Military Education and Training Center in Maradi, Niger date: 2020-08-27 journal: Viruses DOI: 10.3390/v12090949 sha: doc_id: 353365 cord_uid: ujz5nkk3 file: cache/cord-352619-s2x53grh.json key: cord-352619-s2x53grh authors: Payne, Natalie; Kraberger, Simona; Fontenele, Rafaela S; Schmidlin, Kara; Bergeman, Melissa H; Cassaigne, Ivonne; Culver, Melanie; Varsani, Arvind; Van Doorslaer, Koenraad title: Novel Circoviruses Detected in Feces of Sonoran Felids date: 2020-09-15 journal: Viruses DOI: 10.3390/v12091027 sha: doc_id: 352619 cord_uid: s2x53grh file: cache/cord-353609-no3mbg5d.json key: cord-353609-no3mbg5d authors: Vandegrift, Kurt J.; Wale, Nina; Epstein, Jonathan H. title: An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses date: 2011-04-15 journal: Viruses DOI: 10.3390/v3040379 sha: doc_id: 353609 cord_uid: no3mbg5d file: cache/cord-354068-4qlk6y7h.json key: cord-354068-4qlk6y7h authors: Friedrich, Brian M.; Trefry, John C.; Biggins, Julia E.; Hensley, Lisa E.; Honko, Anna N.; Smith, Darci R.; Olinger, Gene G. title: Potential Vaccines and Post-Exposure Treatments for Filovirus Infections date: 2012-09-21 journal: Viruses DOI: 10.3390/v4091619 sha: doc_id: 354068 cord_uid: 4qlk6y7h file: cache/cord-354738-4rxradwz.json key: cord-354738-4rxradwz authors: Kohl, Claudia; Kurth, Andreas title: European Bats as Carriers of Viruses with Zoonotic Potential date: 2014-08-13 journal: Viruses DOI: 10.3390/v6083110 sha: doc_id: 354738 cord_uid: 4rxradwz Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named journal-viruses-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. === 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: 18369 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: 19302 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: 17669 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: 18702 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: 18161 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: 17753 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: 18371 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: 18564 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: 18217 Aborted $FILE2BIB "$FILE" > "$OUTPUT" 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: 15883 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: 17626 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: 18183 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: 18145 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: 18540 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: 18270 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: 18301 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: 15203 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: 18336 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: 18432 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 === file2bib.sh === id: cord-000808-pxryt8wn author: Leroy, Eric title: Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa date: 2012-09-13 pages: extension: .txt txt: ./txt/cord-000808-pxryt8wn.txt cache: ./cache/cord-000808-pxryt8wn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-000808-pxryt8wn.txt' === file2bib.sh === id: cord-003516-l1lq8yga author: Zhang, Jing title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations date: 2019-01-31 pages: extension: .txt txt: ./txt/cord-003516-l1lq8yga.txt cache: ./cache/cord-003516-l1lq8yga.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003516-l1lq8yga.txt' === file2bib.sh === id: cord-002589-xq3iq8ai author: Frossard, Jean-Pierre title: UK Pigs at the Time of Slaughter: Investigation into the Correlation of Infection with PRRSV and HEV date: 2017-06-09 pages: extension: .txt txt: ./txt/cord-002589-xq3iq8ai.txt cache: ./cache/cord-002589-xq3iq8ai.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002589-xq3iq8ai.txt' === file2bib.sh === id: cord-001972-1zisomq5 author: Wang, Xue title: Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells date: 2016-02-02 pages: extension: .txt txt: ./txt/cord-001972-1zisomq5.txt cache: ./cache/cord-001972-1zisomq5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-001972-1zisomq5.txt' === file2bib.sh === id: cord-002076-7t4d4vvo author: Li, Yongfeng title: Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology date: 2016-05-06 pages: extension: .txt txt: ./txt/cord-002076-7t4d4vvo.txt cache: ./cache/cord-002076-7t4d4vvo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002076-7t4d4vvo.txt' === file2bib.sh === id: cord-257665-12gyrmh2 author: Liu, Shan-Lu title: Emerging Viruses without Borders: The Wuhan Coronavirus date: 2020-01-22 pages: extension: .txt txt: ./txt/cord-257665-12gyrmh2.txt cache: ./cache/cord-257665-12gyrmh2.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 1 resourceName b'cord-257665-12gyrmh2.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: 28780 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes 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: 29193 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: 28834 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: 28827 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: 28992 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: 28890 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: 28927 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: 29073 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: 28922 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: 28947 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: 29022 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: 29048 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-002590-24o2viv3 author: Rahe, Michael C. title: Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus date: 2017-06-13 pages: extension: .txt txt: ./txt/cord-002590-24o2viv3.txt cache: ./cache/cord-002590-24o2viv3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002590-24o2viv3.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: 29388 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-252142-aqwlcs9g author: Uematsu, Jun title: Legume Lectins Inhibit Human Parainfluenza Virus Type 2 Infection by Interfering with the Entr date: 2012-06-29 pages: extension: .txt txt: ./txt/cord-252142-aqwlcs9g.txt cache: ./cache/cord-252142-aqwlcs9g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-252142-aqwlcs9g.txt' === file2bib.sh === id: cord-260431-eksl7pp8 author: Sun, Heting title: Isolation and Identification of Feline Herpesvirus Type 1 from a South China Tiger in China date: 2014-02-28 pages: extension: .txt txt: ./txt/cord-260431-eksl7pp8.txt cache: ./cache/cord-260431-eksl7pp8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-260431-eksl7pp8.txt' === file2bib.sh === id: cord-257052-cik2wmlk author: Ban, Junsu title: Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling date: 2018-12-14 pages: extension: .txt txt: ./txt/cord-257052-cik2wmlk.txt cache: ./cache/cord-257052-cik2wmlk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-257052-cik2wmlk.txt' === file2bib.sh === id: cord-257913-uf9sx5qi author: Dijkman, Ronald title: Seroconversion to HCoV-NL63 in Rhesus Macaques date: 2009-10-30 pages: extension: .txt txt: ./txt/cord-257913-uf9sx5qi.txt cache: ./cache/cord-257913-uf9sx5qi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-257913-uf9sx5qi.txt' === file2bib.sh === id: cord-003775-1axsebya author: Lelli, Davide title: Hypsugopoxvirus: A Novel Poxvirus Isolated from Hypsugo savii in Italy date: 2019-06-19 pages: extension: .txt txt: ./txt/cord-003775-1axsebya.txt cache: ./cache/cord-003775-1axsebya.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003775-1axsebya.txt' === file2bib.sh === id: cord-003453-p2buyrcj author: Batista, Mariana N. title: Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus date: 2019-01-11 pages: extension: .txt txt: ./txt/cord-003453-p2buyrcj.txt cache: ./cache/cord-003453-p2buyrcj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003453-p2buyrcj.txt' === file2bib.sh === id: cord-259273-bh5csogu author: Fathima, Sumana title: Use of an Innovative Web-Based Laboratory Surveillance Platform to Analyze Mixed Infections Between Human Metapneumovirus (hMPV) and Other Respiratory Viruses Circulating in Alberta (AB), Canada (2009–2012) date: 2012-11-05 pages: extension: .txt txt: ./txt/cord-259273-bh5csogu.txt cache: ./cache/cord-259273-bh5csogu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-259273-bh5csogu.txt' === file2bib.sh === id: cord-262434-q4tk96tq author: Baker, Kate S. title: Poxviruses in Bats … so What? date: 2014-04-03 pages: extension: .txt txt: ./txt/cord-262434-q4tk96tq.txt cache: ./cache/cord-262434-q4tk96tq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-262434-q4tk96tq.txt' === file2bib.sh === id: cord-002561-7j43yic1 author: Donato, Celeste title: The Broad Host Range and Genetic Diversity of Mammalian and Avian Astroviruses date: 2017-05-10 pages: extension: .txt txt: ./txt/cord-002561-7j43yic1.txt cache: ./cache/cord-002561-7j43yic1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002561-7j43yic1.txt' === file2bib.sh === id: cord-260705-huyyw5z6 author: Moshe, Adi title: Virus-Induced Aggregates in Infected Cells date: 2012-10-17 pages: extension: .txt txt: ./txt/cord-260705-huyyw5z6.txt cache: ./cache/cord-260705-huyyw5z6.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-260705-huyyw5z6.txt' === file2bib.sh === id: cord-003407-f5v3hhr8 author: Hung, Ting-Chun title: Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection date: 2018-11-27 pages: extension: .txt txt: ./txt/cord-003407-f5v3hhr8.txt cache: ./cache/cord-003407-f5v3hhr8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003407-f5v3hhr8.txt' === file2bib.sh === id: cord-004509-jkzqmkz6 author: Thirion, Laurence title: Lyophilized Matrix Containing Ready-to-Use Primers and Probe Solution for Standardization of Real-Time PCR and RT-qPCR Diagnostics in Virology date: 2020-01-30 pages: extension: .txt txt: ./txt/cord-004509-jkzqmkz6.txt cache: ./cache/cord-004509-jkzqmkz6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004509-jkzqmkz6.txt' === file2bib.sh === id: cord-003865-24lz9tf1 author: Zhou, Hongzhuan title: Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells date: 2019-08-13 pages: extension: .txt txt: ./txt/cord-003865-24lz9tf1.txt cache: ./cache/cord-003865-24lz9tf1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003865-24lz9tf1.txt' === file2bib.sh === id: cord-253282-zwl0safn author: Plant, Ewan P. title: Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production date: 2013-01-18 pages: extension: .txt txt: ./txt/cord-253282-zwl0safn.txt cache: ./cache/cord-253282-zwl0safn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-253282-zwl0safn.txt' === file2bib.sh === id: cord-003861-qeao4ghg author: Aris-Brosou, Stéphane title: Viral Long-Term Evolutionary Strategies Favor Stability over Proliferation date: 2019-07-24 pages: extension: .txt txt: ./txt/cord-003861-qeao4ghg.txt cache: ./cache/cord-003861-qeao4ghg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003861-qeao4ghg.txt' === file2bib.sh === id: cord-003917-bswndfvk author: Lalle, Eleonora title: Pulmonary Involvement during the Ebola Virus Disease date: 2019-08-24 pages: extension: .txt txt: ./txt/cord-003917-bswndfvk.txt cache: ./cache/cord-003917-bswndfvk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003917-bswndfvk.txt' === file2bib.sh === id: cord-003646-kjkuet78 author: López-Camacho, César title: Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus date: 2019-04-03 pages: extension: .txt txt: ./txt/cord-003646-kjkuet78.txt cache: ./cache/cord-003646-kjkuet78.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003646-kjkuet78.txt' === file2bib.sh === id: cord-003807-e2txo10z author: Ke, Fei title: Ranaviruses Bind Cells from Different Species through Interaction with Heparan Sulfate date: 2019-06-29 pages: extension: .txt txt: ./txt/cord-003807-e2txo10z.txt cache: ./cache/cord-003807-e2txo10z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003807-e2txo10z.txt' === file2bib.sh === id: cord-258323-vdeffy4l author: Jiang, Yuting title: Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV date: 2019-01-09 pages: extension: .txt txt: ./txt/cord-258323-vdeffy4l.txt cache: ./cache/cord-258323-vdeffy4l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-258323-vdeffy4l.txt' === file2bib.sh === id: cord-002185-oz7hras7 author: Nelson, Elizabeth A. title: Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications date: 2016-08-02 pages: extension: .txt txt: ./txt/cord-002185-oz7hras7.txt cache: ./cache/cord-002185-oz7hras7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002185-oz7hras7.txt' === file2bib.sh === id: cord-256924-c7ftvgio author: Mackay, Ian M. title: Co-circulation of Four Human Coronaviruses (HCoVs) in Queensland Children with Acute Respiratory Tract Illnesses in 2004 date: 2012-04-23 pages: extension: .txt txt: ./txt/cord-256924-c7ftvgio.txt cache: ./cache/cord-256924-c7ftvgio.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-256924-c7ftvgio.txt' === file2bib.sh === id: cord-001974-wjf3c7a7 author: Friis-Nielsen, Jens title: Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers date: 2016-02-19 pages: extension: .txt txt: ./txt/cord-001974-wjf3c7a7.txt cache: ./cache/cord-001974-wjf3c7a7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-001974-wjf3c7a7.txt' === file2bib.sh === id: cord-009399-6zpkpdzu author: Sun, Fang title: Topology, Antiviral Functional Residues and Mechanism of IFITM1 date: 2020-03-08 pages: extension: .txt txt: ./txt/cord-009399-6zpkpdzu.txt cache: ./cache/cord-009399-6zpkpdzu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-009399-6zpkpdzu.txt' === file2bib.sh === id: cord-013177-whd0znan author: Han, Zhenzhi title: The Husavirus Posa-Like Viruses in China, and a New Group of Picornavirales date: 2020-09-07 pages: extension: .txt txt: ./txt/cord-013177-whd0znan.txt cache: ./cache/cord-013177-whd0znan.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-013177-whd0znan.txt' === file2bib.sh === id: cord-003334-ion97n4b author: De Silva Senapathi, Upasama title: The In Ovo Delivery of CpG Oligonucleotides Protects against Infectious Bronchitis with the Recruitment of Immune Cells into the Respiratory Tract of Chickens date: 2018-11-15 pages: extension: .txt txt: ./txt/cord-003334-ion97n4b.txt cache: ./cache/cord-003334-ion97n4b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003334-ion97n4b.txt' === file2bib.sh === id: cord-003961-gs75ebo4 author: Yin, Xin title: Hepatitis E Virus Entry date: 2019-09-20 pages: extension: .txt txt: ./txt/cord-003961-gs75ebo4.txt cache: ./cache/cord-003961-gs75ebo4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003961-gs75ebo4.txt' === file2bib.sh === id: cord-003859-k8wfyj9b author: Paweska, Janusz T. title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera date: 2019-07-24 pages: extension: .txt txt: ./txt/cord-003859-k8wfyj9b.txt cache: ./cache/cord-003859-k8wfyj9b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003859-k8wfyj9b.txt' === file2bib.sh === id: cord-265679-7gzont7l author: Guo, Nan title: Caerin1.1 Suppresses the Growth of Porcine Epidemic Diarrhea Virus In Vitro via Direct Binding to the Virus date: 2018-09-18 pages: extension: .txt txt: ./txt/cord-265679-7gzont7l.txt cache: ./cache/cord-265679-7gzont7l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-265679-7gzont7l.txt' === file2bib.sh === id: cord-004022-cr0zskcw author: Lu, Chien-Yi title: The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles date: 2019-10-31 pages: extension: .txt txt: ./txt/cord-004022-cr0zskcw.txt cache: ./cache/cord-004022-cr0zskcw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004022-cr0zskcw.txt' === file2bib.sh === id: cord-003761-ikni2acz author: Li, Zengbin title: Biological Function and Application of Picornaviral 2B Protein: A New Target for Antiviral Drug Development date: 2019-06-04 pages: extension: .txt txt: ./txt/cord-003761-ikni2acz.txt cache: ./cache/cord-003761-ikni2acz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003761-ikni2acz.txt' === file2bib.sh === id: cord-262499-68vmdqky author: Bordi, Licia title: Frequency and Duration of SARS-CoV-2 Shedding in Oral Fluid Samples Assessed by a Modified Commercial Rapid Molecular Assay date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-262499-68vmdqky.txt cache: ./cache/cord-262499-68vmdqky.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-262499-68vmdqky.txt' === file2bib.sh === id: cord-004337-jtaz1gdp author: Wu, Fangfang title: A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses date: 2020-01-03 pages: extension: .txt txt: ./txt/cord-004337-jtaz1gdp.txt cache: ./cache/cord-004337-jtaz1gdp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 46 resourceName b'cord-004337-jtaz1gdp.txt' === file2bib.sh === id: cord-256713-tlluxd11 author: Welch, David title: Is Network Clustering Detectable in Transmission Trees? date: 2011-06-03 pages: extension: .txt txt: ./txt/cord-256713-tlluxd11.txt cache: ./cache/cord-256713-tlluxd11.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-256713-tlluxd11.txt' === file2bib.sh === id: cord-255683-2eq24jth author: Chen, Weizao title: Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins date: 2010-02-04 pages: extension: .txt txt: ./txt/cord-255683-2eq24jth.txt cache: ./cache/cord-255683-2eq24jth.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-255683-2eq24jth.txt' === file2bib.sh === id: cord-001831-3aonqyub author: Royle, Jamie title: Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals? date: 2015-10-16 pages: extension: .txt txt: ./txt/cord-001831-3aonqyub.txt cache: ./cache/cord-001831-3aonqyub.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-001831-3aonqyub.txt' === file2bib.sh === id: cord-004018-33zi29bg author: Coombs, Kevin M. title: Aptamer Profiling of A549 Cells Infected with Low-Pathogenicity and High-Pathogenicity Influenza Viruses date: 2019-11-05 pages: extension: .txt txt: ./txt/cord-004018-33zi29bg.txt cache: ./cache/cord-004018-33zi29bg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004018-33zi29bg.txt' === file2bib.sh === id: cord-257539-01s21vh0 author: Delvecchio, Rodrigo title: Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models date: 2016-11-29 pages: extension: .txt txt: ./txt/cord-257539-01s21vh0.txt cache: ./cache/cord-257539-01s21vh0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-257539-01s21vh0.txt' === file2bib.sh === id: cord-258536-qnn9hp8e author: Cong, Yingying title: The Interaction between Nidovirales and Autophagy Components date: 2017-07-11 pages: extension: .txt txt: ./txt/cord-258536-qnn9hp8e.txt cache: ./cache/cord-258536-qnn9hp8e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-258536-qnn9hp8e.txt' === file2bib.sh === id: cord-003586-afnto2tz author: Baillet, Nicolas title: Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses date: 2019-03-23 pages: extension: .txt txt: ./txt/cord-003586-afnto2tz.txt cache: ./cache/cord-003586-afnto2tz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003586-afnto2tz.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 3 resourceName b'cord-012497-n5pu1yeu.txt' === 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 === id: cord-004507-ezuyjcxs author: Tomazatos, Alexandru title: Letea Virus: Comparative Genomics and Phylogenetic Analysis of a Novel Reassortant Orbivirus Discovered in Grass Snakes (Natrix natrix) date: 2020-02-21 pages: extension: .txt txt: ./txt/cord-004507-ezuyjcxs.txt cache: ./cache/cord-004507-ezuyjcxs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004507-ezuyjcxs.txt' === file2bib.sh === id: cord-004020-qtwcbn7m author: Gao, Yaning title: Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors date: 2019-11-02 pages: extension: .txt txt: ./txt/cord-004020-qtwcbn7m.txt cache: ./cache/cord-004020-qtwcbn7m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004020-qtwcbn7m.txt' === file2bib.sh === id: cord-263315-g7os15m1 author: Martins-da-Silva, Andrea title: Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response date: 2018-01-18 pages: extension: .txt txt: ./txt/cord-263315-g7os15m1.txt cache: ./cache/cord-263315-g7os15m1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-263315-g7os15m1.txt' === file2bib.sh === id: cord-272459-w14finxf author: Heaton, Nicholas S. title: Dengue Virus and Autophagy date: 2011-08-04 pages: extension: .txt txt: ./txt/cord-272459-w14finxf.txt cache: ./cache/cord-272459-w14finxf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-272459-w14finxf.txt' === file2bib.sh === id: cord-267709-i2loz1xb author: Li, Tongya title: Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200 date: 2019-05-09 pages: extension: .txt txt: ./txt/cord-267709-i2loz1xb.txt cache: ./cache/cord-267709-i2loz1xb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-267709-i2loz1xb.txt' === file2bib.sh === id: cord-013174-whg64w0w author: Bhatta, Tarka Raj title: Infection Dynamics of Swine Influenza Virus in a Danish Pig Herd Reveals Recurrent Infections with Different Variants of the H1N2 Swine Influenza A Virus Subtype date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-013174-whg64w0w.txt cache: ./cache/cord-013174-whg64w0w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-013174-whg64w0w.txt' === file2bib.sh === id: cord-254250-l0v602x9 author: Hooper, Chantelle title: A Novel RNA Virus, Macrobrachium rosenbergii Golda Virus (MrGV), Linked to Mass Mortalities of the Larval Giant Freshwater Prawn in Bangladesh date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-254250-l0v602x9.txt cache: ./cache/cord-254250-l0v602x9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-254250-l0v602x9.txt' === file2bib.sh === id: cord-254181-nquozaxt author: Sieg, Michael title: A New Genotype of Feline Morbillivirus Infects Primary Cells of the Lung, Kidney, Brain and Peripheral Blood date: 2019-02-09 pages: extension: .txt txt: ./txt/cord-254181-nquozaxt.txt cache: ./cache/cord-254181-nquozaxt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-254181-nquozaxt.txt' === file2bib.sh === id: cord-261417-4pf5nsw2 author: Harwig, Alex title: The Battle of RNA Synthesis: Virus versus Host date: 2017-10-21 pages: extension: .txt txt: ./txt/cord-261417-4pf5nsw2.txt cache: ./cache/cord-261417-4pf5nsw2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 15 resourceName b'cord-261417-4pf5nsw2.txt' === file2bib.sh === id: cord-003915-kje8lvgl author: Pigeyre, Laetitia title: Interaction of a Densovirus with Glycans of the Peritrophic Matrix Mediates Oral Infection of the Lepidopteran Pest Spodoptera frugiperda date: 2019-09-17 pages: extension: .txt txt: ./txt/cord-003915-kje8lvgl.txt cache: ./cache/cord-003915-kje8lvgl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003915-kje8lvgl.txt' === file2bib.sh === id: cord-272010-kc0gi3cj author: Anand, Sai Priya title: Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-272010-kc0gi3cj.txt cache: ./cache/cord-272010-kc0gi3cj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-272010-kc0gi3cj.txt' === file2bib.sh === id: cord-003772-1345qct4 author: Kummer, Susann title: IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells date: 2019-06-12 pages: extension: .txt txt: ./txt/cord-003772-1345qct4.txt cache: ./cache/cord-003772-1345qct4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003772-1345qct4.txt' === file2bib.sh === id: cord-267733-fuz8r3vj author: Al Ali, Sally title: Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors date: 2016-05-21 pages: extension: .txt txt: ./txt/cord-267733-fuz8r3vj.txt cache: ./cache/cord-267733-fuz8r3vj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-267733-fuz8r3vj.txt' === file2bib.sh === 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 pages: extension: .txt txt: ./txt/cord-004334-y1fcw1dj.txt cache: ./cache/cord-004334-y1fcw1dj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004334-y1fcw1dj.txt' === file2bib.sh === id: cord-011635-vosu7y6j author: Norlander, Allison E. title: Innate Type 2 Responses to Respiratory Syncytial Virus Infection date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-011635-vosu7y6j.txt cache: ./cache/cord-011635-vosu7y6j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-011635-vosu7y6j.txt' === file2bib.sh === id: cord-011435-x73foqu7 author: Glanz, Anna title: High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-011435-x73foqu7.txt cache: ./cache/cord-011435-x73foqu7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-011435-x73foqu7.txt' === file2bib.sh === id: cord-263142-o8qbqxhx author: Cavalcante, Liliane T. F. title: Clinical and Molecular Features of Feline Foamy Virus and Feline Leukemia Virus Co-Infection in Naturally-Infected Cats date: 2018-12-11 pages: extension: .txt txt: ./txt/cord-263142-o8qbqxhx.txt cache: ./cache/cord-263142-o8qbqxhx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-263142-o8qbqxhx.txt' === file2bib.sh === id: cord-003284-hjx2d5rq author: Márquez-Jurado, Silvia title: An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo date: 2018-10-07 pages: extension: .txt txt: ./txt/cord-003284-hjx2d5rq.txt cache: ./cache/cord-003284-hjx2d5rq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003284-hjx2d5rq.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes 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 pages: extension: .txt txt: ./txt/cord-270103-g9a72xf6.txt cache: ./cache/cord-270103-g9a72xf6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-270103-g9a72xf6.txt' === file2bib.sh === id: cord-004508-ok3px98z author: Armando, Federico title: Oxidative Stress in Canine Histiocytic Sarcoma Cells Induced by an Infection with Canine Distemper Virus Led to a Dysregulation of HIF-1α Downstream Pathway Resulting in a Reduced Expression of VEGF-B In Vitro date: 2020-02-11 pages: extension: .txt txt: ./txt/cord-004508-ok3px98z.txt cache: ./cache/cord-004508-ok3px98z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004508-ok3px98z.txt' === file2bib.sh === id: cord-259237-aty0vrat author: Frabutt, Dylan A. title: Arms Race between Enveloped Viruses and the Host ERAD Machinery date: 2016-09-19 pages: extension: .txt txt: ./txt/cord-259237-aty0vrat.txt cache: ./cache/cord-259237-aty0vrat.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-259237-aty0vrat.txt' === file2bib.sh === id: cord-003130-p2h8p5bm author: Lindqvist, Richard title: Tick-Borne Flaviviruses and the Type I Interferon Response date: 2018-06-21 pages: extension: .txt txt: ./txt/cord-003130-p2h8p5bm.txt cache: ./cache/cord-003130-p2h8p5bm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003130-p2h8p5bm.txt' === file2bib.sh === id: cord-281552-zfjy3m3i author: Alsaadi, Entedar A. J. title: Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-281552-zfjy3m3i.txt cache: ./cache/cord-281552-zfjy3m3i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-281552-zfjy3m3i.txt' === file2bib.sh === id: cord-012420-llh22iq2 author: Stott, Robert J. title: Distinct Molecular Mechanisms of Host Immune Response Modulation by Arenavirus NP and Z Proteins date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-012420-llh22iq2.txt cache: ./cache/cord-012420-llh22iq2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-012420-llh22iq2.txt' === file2bib.sh === id: cord-281837-knswbb2d author: Chang, Chia-Wen title: Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry date: 2012-04-11 pages: extension: .txt txt: ./txt/cord-281837-knswbb2d.txt cache: ./cache/cord-281837-knswbb2d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-281837-knswbb2d.txt' === file2bib.sh === id: cord-002691-synm1cyw author: Hou, Jiun-Nan title: PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication date: 2017-09-20 pages: extension: .txt txt: ./txt/cord-002691-synm1cyw.txt cache: ./cache/cord-002691-synm1cyw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002691-synm1cyw.txt' === file2bib.sh === id: cord-003962-lg6gvgwt author: Zhou, Shaochuan title: Characterizing the PRRSV nsp2 Deubiquitinase Reveals Dispensability of Cis-Activity for Replication and a Link of nsp2 to Inflammation Induction date: 2019-09-26 pages: extension: .txt txt: ./txt/cord-003962-lg6gvgwt.txt cache: ./cache/cord-003962-lg6gvgwt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003962-lg6gvgwt.txt' === file2bib.sh === id: cord-011438-imbpgsub author: Zhang, Yun title: Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection date: 2020-03-29 pages: extension: .txt txt: ./txt/cord-011438-imbpgsub.txt cache: ./cache/cord-011438-imbpgsub.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-011438-imbpgsub.txt' === file2bib.sh === id: cord-013178-li1x1m25 author: Hung, Ling-Chu title: The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells date: 2020-08-29 pages: extension: .txt txt: ./txt/cord-013178-li1x1m25.txt cache: ./cache/cord-013178-li1x1m25.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-013178-li1x1m25.txt' === file2bib.sh === id: cord-002808-84np9brx author: Campos, Samuel K. title: Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2 date: 2017-12-03 pages: extension: .txt txt: ./txt/cord-002808-84np9brx.txt cache: ./cache/cord-002808-84np9brx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002808-84np9brx.txt' === file2bib.sh === id: cord-002994-1zjrunzc author: Faye, Martin title: Full-Genome Characterization and Genetic Evolution of West African Isolates of Bagaza Virus date: 2018-04-13 pages: extension: .txt txt: ./txt/cord-002994-1zjrunzc.txt cache: ./cache/cord-002994-1zjrunzc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002994-1zjrunzc.txt' === file2bib.sh === id: cord-287647-0nyquokt author: Nemoto, Manabu title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland date: 2019-10-14 pages: extension: .txt txt: ./txt/cord-287647-0nyquokt.txt cache: ./cache/cord-287647-0nyquokt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-287647-0nyquokt.txt' === file2bib.sh === id: cord-273326-gmw8gl2r author: Saiz, Juan-Carlos title: Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus date: 2018-08-24 pages: extension: .txt txt: ./txt/cord-273326-gmw8gl2r.txt cache: ./cache/cord-273326-gmw8gl2r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-273326-gmw8gl2r.txt' === file2bib.sh === id: cord-289757-jtvpfsiu author: Abrams, Anna title: The Prevalence and Significance of HTLV-I/II Seroindeterminate Western Blot Patterns date: 2011-08-02 pages: extension: .txt txt: ./txt/cord-289757-jtvpfsiu.txt cache: ./cache/cord-289757-jtvpfsiu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-289757-jtvpfsiu.txt' === file2bib.sh === id: cord-267012-45tre8rn author: Premanand, Balraj title: Baculovirus Surface Display of Immunogenic Proteins for Vaccine Development date: 2018-05-31 pages: extension: .txt txt: ./txt/cord-267012-45tre8rn.txt cache: ./cache/cord-267012-45tre8rn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-267012-45tre8rn.txt' === file2bib.sh === id: cord-292364-jhiimglg author: Hayakawa, Jun title: Genetic and Antigenic Characterization and Retrospective Surveillance of Bovine Influenza D Viruses Identified in Hokkaido, Japan from 2018 to 2020 date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-292364-jhiimglg.txt cache: ./cache/cord-292364-jhiimglg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-292364-jhiimglg.txt' === file2bib.sh === id: cord-273366-xd84f8ct author: Brownsword, Matthew J. title: Infectious Bronchitis Virus Regulates Cellular Stress Granule Signaling date: 2020-05-14 pages: extension: .txt txt: ./txt/cord-273366-xd84f8ct.txt cache: ./cache/cord-273366-xd84f8ct.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-273366-xd84f8ct.txt' === file2bib.sh === id: cord-295750-0gpyi4ii author: Raev, Sergei title: An Outbreak of a Respiratory Disorder at a Russian Swine Farm Associated with the Co-Circulation of PRRSV1 and PRRSV2 date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-295750-0gpyi4ii.txt cache: ./cache/cord-295750-0gpyi4ii.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-295750-0gpyi4ii.txt' === file2bib.sh === id: cord-000804-0hlj6r10 author: Brauburger, Kristina title: Forty-Five Years of Marburg Virus Research date: 2012-10-01 pages: extension: .txt txt: ./txt/cord-000804-0hlj6r10.txt cache: ./cache/cord-000804-0hlj6r10.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-000804-0hlj6r10.txt' === file2bib.sh === id: cord-286343-s8n1ldol author: Martin, Javier title: Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-286343-s8n1ldol.txt cache: ./cache/cord-286343-s8n1ldol.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-286343-s8n1ldol.txt' === file2bib.sh === id: cord-292948-1n5ej08f author: Masse, Shirley title: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014–2020) in France date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-292948-1n5ej08f.txt cache: ./cache/cord-292948-1n5ej08f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-292948-1n5ej08f.txt' === file2bib.sh === id: cord-295044-eva0soja author: Hutson, Christina L. title: Monkeypox Virus Infections in Small Animal Models for Evaluation of Anti-Poxvirus Agents date: 2010-12-20 pages: extension: .txt txt: ./txt/cord-295044-eva0soja.txt cache: ./cache/cord-295044-eva0soja.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-295044-eva0soja.txt' === file2bib.sh === id: cord-296736-jsm6o5pq author: Chidlow, Glenys R. title: An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens date: 2009-06-08 pages: extension: .txt txt: ./txt/cord-296736-jsm6o5pq.txt cache: ./cache/cord-296736-jsm6o5pq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-296736-jsm6o5pq.txt' === file2bib.sh === id: cord-309239-6lso1w0o author: Adney, Danielle R. title: Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding date: 2016-08-19 pages: extension: .txt txt: ./txt/cord-309239-6lso1w0o.txt cache: ./cache/cord-309239-6lso1w0o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-309239-6lso1w0o.txt' === file2bib.sh === id: cord-288058-oilurica author: Cui, Tingting title: Role of Porcine Aminopeptidase N and Sialic Acids in Porcine Coronavirus Infections in Primary Porcine Enterocytes date: 2020-04-05 pages: extension: .txt txt: ./txt/cord-288058-oilurica.txt cache: ./cache/cord-288058-oilurica.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-288058-oilurica.txt' === file2bib.sh === 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 pages: extension: .txt txt: ./txt/cord-012418-6ralcn8p.txt cache: ./cache/cord-012418-6ralcn8p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-012418-6ralcn8p.txt' === file2bib.sh === id: cord-292050-x3isowrt author: Ackerman, Emily E. title: Network Controllability-Based Prioritization of Candidates for SARS-CoV-2 Drug Repositioning date: 2020-09-26 pages: extension: .txt txt: ./txt/cord-292050-x3isowrt.txt cache: ./cache/cord-292050-x3isowrt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-292050-x3isowrt.txt' === file2bib.sh === id: cord-288556-o8i6j3b2 author: Li, Yanpeng title: Virome of a Feline Outbreak of Diarrhea and Vomiting Includes Bocaviruses and a Novel Chapparvovirus date: 2020-05-04 pages: extension: .txt txt: ./txt/cord-288556-o8i6j3b2.txt cache: ./cache/cord-288556-o8i6j3b2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-288556-o8i6j3b2.txt' === file2bib.sh === id: cord-294347-axkdf5vu author: Kim, Shin-Hee title: Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines date: 2016-07-04 pages: extension: .txt txt: ./txt/cord-294347-axkdf5vu.txt cache: ./cache/cord-294347-axkdf5vu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-294347-axkdf5vu.txt' === file2bib.sh === id: cord-297339-et2305rz author: Lauber, Chris title: Genetics-Based Classification of Filoviruses Calls for Expanded Sampling of Genomic Sequences date: 2012-08-31 pages: extension: .txt txt: ./txt/cord-297339-et2305rz.txt cache: ./cache/cord-297339-et2305rz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-297339-et2305rz.txt' === file2bib.sh === id: cord-301633-t8s4s0wo author: Gralinski, Lisa E. title: Return of the Coronavirus: 2019-nCoV date: 2020-01-24 pages: extension: .txt txt: ./txt/cord-301633-t8s4s0wo.txt cache: ./cache/cord-301633-t8s4s0wo.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 3 resourceName b'cord-301633-t8s4s0wo.txt' === file2bib.sh === id: cord-285935-5rsk6g7l author: Kinast, Volker title: Hepatitis E Virus Drug Development date: 2019-05-28 pages: extension: .txt txt: ./txt/cord-285935-5rsk6g7l.txt cache: ./cache/cord-285935-5rsk6g7l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-285935-5rsk6g7l.txt' === file2bib.sh === id: cord-305857-2409me0p author: López-Roig, Marc title: Seroprevalence Dynamics of European Bat Lyssavirus Type 1 in a Multispecies Bat Colony date: 2014-09-04 pages: extension: .txt txt: ./txt/cord-305857-2409me0p.txt cache: ./cache/cord-305857-2409me0p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-305857-2409me0p.txt' === file2bib.sh === id: cord-295433-olmein3q author: Banerjee, Arinjay title: Bats and Coronaviruses date: 2019-01-09 pages: extension: .txt txt: ./txt/cord-295433-olmein3q.txt cache: ./cache/cord-295433-olmein3q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-295433-olmein3q.txt' === file2bib.sh === id: cord-310579-tnxokfwu author: Kim, Sung-Jae title: Molecular Characterization of Porcine Epidemic Diarrhea Virus and Its New Genetic Classification Based on the Nucleocapsid Gene date: 2020-07-23 pages: extension: .txt txt: ./txt/cord-310579-tnxokfwu.txt cache: ./cache/cord-310579-tnxokfwu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-310579-tnxokfwu.txt' === file2bib.sh === id: cord-297092-oq14cwka author: Tan, Shaoyuan title: Characterization of Emerging Swine Viral Diseases through Oxford Nanopore Sequencing Using Senecavirus A as a Model date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-297092-oq14cwka.txt cache: ./cache/cord-297092-oq14cwka.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-297092-oq14cwka.txt' === file2bib.sh === id: cord-306004-amv0los1 author: Widagdo, W. title: Host Determinants of MERS-CoV Transmission and Pathogenesis date: 2019-03-19 pages: extension: .txt txt: ./txt/cord-306004-amv0los1.txt cache: ./cache/cord-306004-amv0los1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-306004-amv0los1.txt' === file2bib.sh === id: cord-289273-zpyz1krq author: Barry, Michele title: Poxvirus Exploitation of the Ubiquitin-Proteasome System date: 2010-10-19 pages: extension: .txt txt: ./txt/cord-289273-zpyz1krq.txt cache: ./cache/cord-289273-zpyz1krq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-289273-zpyz1krq.txt' === file2bib.sh === id: cord-311205-3uwiys4a author: Hung, Yu-Fu title: Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes date: 2015-07-21 pages: extension: .txt txt: ./txt/cord-311205-3uwiys4a.txt cache: ./cache/cord-311205-3uwiys4a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-311205-3uwiys4a.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 === id: cord-309623-2ngr682l author: Han, Xiaoxiao title: Infectious Bronchitis Virus Infection Induces Apoptosis during Replication in Chicken Macrophage HD11 Cells date: 2017-07-26 pages: extension: .txt txt: ./txt/cord-309623-2ngr682l.txt cache: ./cache/cord-309623-2ngr682l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-309623-2ngr682l.txt' === file2bib.sh === id: cord-320921-eumuid3r author: Widagdo, W. title: Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits date: 2019-04-24 pages: extension: .txt txt: ./txt/cord-320921-eumuid3r.txt cache: ./cache/cord-320921-eumuid3r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-320921-eumuid3r.txt' === file2bib.sh === id: cord-290127-51ljxy72 author: Al-Kassmy, Jawad title: Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand? date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-290127-51ljxy72.txt cache: ./cache/cord-290127-51ljxy72.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-290127-51ljxy72.txt' === file2bib.sh === id: cord-302716-wfla3l20 author: Popov, Vsevolod L. title: Electron Microscopy in Discovery of Novel and Emerging Viruses from the Collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) date: 2019-05-25 pages: extension: .txt txt: ./txt/cord-302716-wfla3l20.txt cache: ./cache/cord-302716-wfla3l20.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-302716-wfla3l20.txt' === file2bib.sh === id: cord-297834-me1ajoyb author: Schountz, Tony title: Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions date: 2014-03-14 pages: extension: .txt txt: ./txt/cord-297834-me1ajoyb.txt cache: ./cache/cord-297834-me1ajoyb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-297834-me1ajoyb.txt' === file2bib.sh === id: cord-309635-1tgovkr7 author: Wu, Nicholas C. title: Structural Biology of Influenza Hemagglutinin: An Amaranthine Adventure date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-309635-1tgovkr7.txt cache: ./cache/cord-309635-1tgovkr7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-309635-1tgovkr7.txt' === file2bib.sh === id: cord-296819-gztmidn2 author: Sambri, Vittorio title: Diagnosis of West Nile Virus Human Infections: Overview and Proposal of Diagnostic Protocols Considering the Results of External Quality Assessment Studies date: 2013-09-25 pages: extension: .txt txt: ./txt/cord-296819-gztmidn2.txt cache: ./cache/cord-296819-gztmidn2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-296819-gztmidn2.txt' === file2bib.sh === id: cord-310255-aixq5mhf author: Charlton, Frank W. title: Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives date: 2020-08-03 pages: extension: .txt txt: ./txt/cord-310255-aixq5mhf.txt cache: ./cache/cord-310255-aixq5mhf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-310255-aixq5mhf.txt' === file2bib.sh === id: cord-325823-bt7xo9iq author: Magassouba, N’Faly title: A Sporadic and Lethal Lassa Fever Case in Forest Guinea, 2019 date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-325823-bt7xo9iq.txt cache: ./cache/cord-325823-bt7xo9iq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-325823-bt7xo9iq.txt' === file2bib.sh === id: cord-300625-fvirvpyl author: Srinivasan, Suhas title: Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins date: 2020-03-25 pages: extension: .txt txt: ./txt/cord-300625-fvirvpyl.txt cache: ./cache/cord-300625-fvirvpyl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-300625-fvirvpyl.txt' === file2bib.sh === id: cord-301810-vtgdqart author: Aston, Emily J. title: Effect of Pullet Vaccination on Development and Longevity of Immunity date: 2019-02-02 pages: extension: .txt txt: ./txt/cord-301810-vtgdqart.txt cache: ./cache/cord-301810-vtgdqart.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-301810-vtgdqart.txt' === file2bib.sh === id: cord-309571-a0xu1d56 author: Aboughdir, Maryam title: Prognostic Value of Cardiovascular Biomarkers in COVID-19: A Review date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-309571-a0xu1d56.txt cache: ./cache/cord-309571-a0xu1d56.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 3 resourceName b'cord-309571-a0xu1d56.txt' === file2bib.sh === id: cord-307110-eiobmxp2 author: Zhao, Shan title: Serological Screening for Coronavirus Infections in Cats date: 2019-08-13 pages: extension: .txt txt: ./txt/cord-307110-eiobmxp2.txt cache: ./cache/cord-307110-eiobmxp2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-307110-eiobmxp2.txt' === file2bib.sh === id: cord-314891-brgtwxhe author: Fumian, Tulio M. title: Potential Therapeutic Agents for Feline Calicivirus Infection date: 2018-08-16 pages: extension: .txt txt: ./txt/cord-314891-brgtwxhe.txt cache: ./cache/cord-314891-brgtwxhe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-314891-brgtwxhe.txt' === file2bib.sh === id: cord-317026-9zgc6xrb author: Zhao, Shan title: Development and Validation of a S1 Protein-Based ELISA for the Specific Detection of Antibodies against Equine Coronavirus date: 2019-11-30 pages: extension: .txt txt: ./txt/cord-317026-9zgc6xrb.txt cache: ./cache/cord-317026-9zgc6xrb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-317026-9zgc6xrb.txt' === file2bib.sh === id: cord-321080-pgxxkfc0 author: Wang, Cong title: Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD date: 2019-01-06 pages: extension: .txt txt: ./txt/cord-321080-pgxxkfc0.txt cache: ./cache/cord-321080-pgxxkfc0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-321080-pgxxkfc0.txt' === file2bib.sh === id: cord-313161-07iwwsfz author: Lundstrom, Kenneth title: Alphavirus-Based Vaccines date: 2014-06-16 pages: extension: .txt txt: ./txt/cord-313161-07iwwsfz.txt cache: ./cache/cord-313161-07iwwsfz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-313161-07iwwsfz.txt' === file2bib.sh === id: cord-335279-cfv18qn0 author: Paillot, Romain title: Special Issue “Equine Viruses”: Old “Friends” and New Foes? date: 2020-01-29 pages: extension: .txt txt: ./txt/cord-335279-cfv18qn0.txt cache: ./cache/cord-335279-cfv18qn0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-335279-cfv18qn0.txt' === file2bib.sh === id: cord-322206-roxa3ix6 author: I. Sardi, Silvia title: High-Quality Resolution of the Outbreak-Related Zika Virus Genome and Discovery of New Viruses Using Ion Torrent-Based Metatranscriptomics date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-322206-roxa3ix6.txt cache: ./cache/cord-322206-roxa3ix6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-322206-roxa3ix6.txt' === file2bib.sh === id: cord-314340-ltx4w9zh author: Zhu, Liqian title: The Involvement of Histone H3 Acetylation in Bovine Herpesvirus 1 Replication in MDBK Cells date: 2018-09-27 pages: extension: .txt txt: ./txt/cord-314340-ltx4w9zh.txt cache: ./cache/cord-314340-ltx4w9zh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-314340-ltx4w9zh.txt' === file2bib.sh === id: cord-309693-f2htekhz author: Yu, Meiling title: Immunogenicity of eGFP-Marked Recombinant Lactobacillus casei against Transmissible Gastroenteritis Virus and Porcine Epidemic Diarrhea Virus date: 2017-09-25 pages: extension: .txt txt: ./txt/cord-309693-f2htekhz.txt cache: ./cache/cord-309693-f2htekhz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-309693-f2htekhz.txt' === file2bib.sh === id: cord-325574-4zf9qtlh author: Farag, Elmoubasher title: Drivers of MERS-CoV Emergence in Qatar date: 2018-12-31 pages: extension: .txt txt: ./txt/cord-325574-4zf9qtlh.txt cache: ./cache/cord-325574-4zf9qtlh.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 3 resourceName b'cord-325574-4zf9qtlh.txt' === file2bib.sh === id: cord-312272-g4n426cm author: Matczuk, Anna Karolina title: Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells date: 2019-08-09 pages: extension: .txt txt: ./txt/cord-312272-g4n426cm.txt cache: ./cache/cord-312272-g4n426cm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-312272-g4n426cm.txt' === file2bib.sh === id: cord-320212-fw51w4nm author: Friedman, Stephanie D. title: Genomic Sequences of two Novel Levivirus Single-Stranded RNA Coliphages (Family Leviviridae): Evidence for Recombinationin Environmental Strains date: 2012-09-13 pages: extension: .txt txt: ./txt/cord-320212-fw51w4nm.txt cache: ./cache/cord-320212-fw51w4nm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-320212-fw51w4nm.txt' === file2bib.sh === id: cord-331414-i0oxm5mr author: Kautz, Tiffany F. title: A Low Fidelity Virus Shows Increased Recombination during the Removal of an Alphavirus Reporter Gene date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-331414-i0oxm5mr.txt cache: ./cache/cord-331414-i0oxm5mr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-331414-i0oxm5mr.txt' === file2bib.sh === id: cord-315164-nidgnvvi author: Medkour, Hacène title: Adenovirus Infections in African Humans and Wild Non-Human Primates: Great Diversity and Cross-Species Transmission date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-315164-nidgnvvi.txt cache: ./cache/cord-315164-nidgnvvi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-315164-nidgnvvi.txt' === file2bib.sh === id: cord-313312-h607itv2 author: Mok, Darren Z. L. title: The Effects of Pre-Existing Antibodies on Live-Attenuated Viral Vaccines date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-313312-h607itv2.txt cache: ./cache/cord-313312-h607itv2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-313312-h607itv2.txt' === file2bib.sh === id: cord-323585-iv2dcpqj author: Li, Su title: eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus date: 2015-08-10 pages: extension: .txt txt: ./txt/cord-323585-iv2dcpqj.txt cache: ./cache/cord-323585-iv2dcpqj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-323585-iv2dcpqj.txt' === file2bib.sh === id: cord-323569-ksodnkic author: Xu, Shengnan title: A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice date: 2019-12-11 pages: extension: .txt txt: ./txt/cord-323569-ksodnkic.txt cache: ./cache/cord-323569-ksodnkic.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-323569-ksodnkic.txt' === file2bib.sh === id: cord-330475-mameyzih author: Shi, Da title: Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus date: 2014-03-13 pages: extension: .txt txt: ./txt/cord-330475-mameyzih.txt cache: ./cache/cord-330475-mameyzih.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-330475-mameyzih.txt' === file2bib.sh === id: cord-317496-6o2upns3 author: Pascual-Iglesias, Alejandro title: Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV)—Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV date: 2019-07-25 pages: extension: .txt txt: ./txt/cord-317496-6o2upns3.txt cache: ./cache/cord-317496-6o2upns3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-317496-6o2upns3.txt' === file2bib.sh === id: cord-283756-ycjzitlk author: Simons, Robin R. L. title: Potential for Introduction of Bat-Borne Zoonotic Viruses into the EU: A Review date: 2014-05-16 pages: extension: .txt txt: ./txt/cord-283756-ycjzitlk.txt cache: ./cache/cord-283756-ycjzitlk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-283756-ycjzitlk.txt' === file2bib.sh === id: cord-317715-xtsi663k author: Ortiz-Riaño, Emilio title: D471G Mutation in LCMV-NP Affects its Ability to Self-associate and Results in a Dominant Negative Effect in Viral RNA Synthesis date: 2012-10-16 pages: extension: .txt txt: ./txt/cord-317715-xtsi663k.txt cache: ./cache/cord-317715-xtsi663k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-317715-xtsi663k.txt' === file2bib.sh === id: cord-324617-yok7mh70 author: Andreata-Santos, Robert title: Transcutaneous Administration of Dengue Vaccines date: 2020-05-06 pages: extension: .txt txt: ./txt/cord-324617-yok7mh70.txt cache: ./cache/cord-324617-yok7mh70.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-324617-yok7mh70.txt' === file2bib.sh === id: cord-337339-0vkigjv2 author: Osterrieder, Nikolaus title: Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters date: 2020-07-20 pages: extension: .txt txt: ./txt/cord-337339-0vkigjv2.txt cache: ./cache/cord-337339-0vkigjv2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-337339-0vkigjv2.txt' === file2bib.sh === id: cord-332915-4o2dsf56 author: Hong, Seung-Min title: Pathobiological and Genomic Characterization of a Cold-Adapted Infectious Bronchitis Virus (BP-caKII) date: 2018-11-19 pages: extension: .txt txt: ./txt/cord-332915-4o2dsf56.txt cache: ./cache/cord-332915-4o2dsf56.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-332915-4o2dsf56.txt' === file2bib.sh === id: cord-332165-31tbc31x author: Rustmeier, Nils H. title: The Symmetry of Viral Sialic Acid Binding Sites—Implications for Antiviral Strategies date: 2019-10-14 pages: extension: .txt txt: ./txt/cord-332165-31tbc31x.txt cache: ./cache/cord-332165-31tbc31x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-332165-31tbc31x.txt' === file2bib.sh === id: cord-308201-lavcsqov author: Desforges, Marc title: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? date: 2019-12-20 pages: extension: .txt txt: ./txt/cord-308201-lavcsqov.txt cache: ./cache/cord-308201-lavcsqov.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-308201-lavcsqov.txt' === file2bib.sh === id: cord-328042-e1is656g author: Klein, Steffen title: SARS-CoV-2 RNA Extraction Using Magnetic Beads for Rapid Large-Scale Testing by RT-qPCR and RT-LAMP date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-328042-e1is656g.txt cache: ./cache/cord-328042-e1is656g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-328042-e1is656g.txt' === file2bib.sh === id: cord-330767-jja2wcfz author: Voigt, Kathleen title: Fusogenicity of the Ghana Virus (Henipavirus: Ghanaian bat henipavirus) Fusion Protein is Controlled by the Cytoplasmic Domain of the Attachment Glycoprotein date: 2019-08-29 pages: extension: .txt txt: ./txt/cord-330767-jja2wcfz.txt cache: ./cache/cord-330767-jja2wcfz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-330767-jja2wcfz.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-310734-6v7oru2l author: Bolatti, Elisa M. title: A Preliminary Study of the Virome of the South American Free-Tailed Bats (Tadarida brasiliensis) and Identification of Two Novel Mammalian Viruses date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-310734-6v7oru2l.txt cache: ./cache/cord-310734-6v7oru2l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-310734-6v7oru2l.txt' === file2bib.sh === id: cord-294842-aesiff1f author: Romero-Brey, Inés title: Membranous Replication Factories Induced by Plus-Strand RNA Viruses date: 2014-07-22 pages: extension: .txt txt: ./txt/cord-294842-aesiff1f.txt cache: ./cache/cord-294842-aesiff1f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-294842-aesiff1f.txt' === file2bib.sh === id: cord-334855-s0ci3r8w author: Andersen, Petter I. title: Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine date: 2019-10-18 pages: extension: .txt txt: ./txt/cord-334855-s0ci3r8w.txt cache: ./cache/cord-334855-s0ci3r8w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-334855-s0ci3r8w.txt' === file2bib.sh === id: cord-326319-3538jmqd author: Yuan, Yuan title: Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins date: 2018-06-27 pages: extension: .txt txt: ./txt/cord-326319-3538jmqd.txt cache: ./cache/cord-326319-3538jmqd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-326319-3538jmqd.txt' === file2bib.sh === id: cord-332576-pd62s65y author: Lu, Chien-Yi title: Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus date: 2017-04-10 pages: extension: .txt txt: ./txt/cord-332576-pd62s65y.txt cache: ./cache/cord-332576-pd62s65y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-332576-pd62s65y.txt' === file2bib.sh === id: cord-320015-lbr2q4qh author: Chinchar, V. Gregory title: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date: 2011-10-20 pages: extension: .txt txt: ./txt/cord-320015-lbr2q4qh.txt cache: ./cache/cord-320015-lbr2q4qh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-320015-lbr2q4qh.txt' === file2bib.sh === id: cord-331094-22366b81 author: Ianevski, Aleksandr title: Potential Antiviral Options against SARS-CoV-2 Infection date: 2020-06-13 pages: extension: .txt txt: ./txt/cord-331094-22366b81.txt cache: ./cache/cord-331094-22366b81.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-331094-22366b81.txt' === file2bib.sh === id: cord-328259-3g4klpyg author: Guajardo-Leiva, Sergio title: Metagenomic Insights into the Sewage RNA Virosphere of a Large City date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-328259-3g4klpyg.txt cache: ./cache/cord-328259-3g4klpyg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-328259-3g4klpyg.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-311008-b7xjlqg3 author: Zapatero-Belinchón, Francisco J. title: Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors date: 2019-03-19 pages: extension: .txt txt: ./txt/cord-311008-b7xjlqg3.txt cache: ./cache/cord-311008-b7xjlqg3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-311008-b7xjlqg3.txt' === file2bib.sh === id: cord-309378-sfr1x0ob author: Röst, Gergely title: Early Phase of the COVID-19 Outbreak in Hungary and Post-Lockdown Scenarios date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-309378-sfr1x0ob.txt cache: ./cache/cord-309378-sfr1x0ob.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-309378-sfr1x0ob.txt' === file2bib.sh === id: cord-334560-1j9zmuub author: Hunt, Catherine L. title: Filovirus Entry: A Novelty in the Viral Fusion World date: 2012-02-07 pages: extension: .txt txt: ./txt/cord-334560-1j9zmuub.txt cache: ./cache/cord-334560-1j9zmuub.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-334560-1j9zmuub.txt' === file2bib.sh === id: cord-321673-v5o49ees author: Nieto-Torres, Jose L. title: Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis date: 2015-07-03 pages: extension: .txt txt: ./txt/cord-321673-v5o49ees.txt cache: ./cache/cord-321673-v5o49ees.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-321673-v5o49ees.txt' === file2bib.sh === id: cord-321441-t1v0pu0w author: Yang, Yiming title: Polycistronic Genome Segment Evolution and Gain and Loss of FAST Protein Function during Fusogenic Orthoreovirus Speciation date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-321441-t1v0pu0w.txt cache: ./cache/cord-321441-t1v0pu0w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-321441-t1v0pu0w.txt' === file2bib.sh === id: cord-339752-o6atz33c author: Xiao, Li title: ACE2: The Key Molecule for Understanding the Pathophysiology of Severe and Critical Conditions of COVID-19: Demon or Angel? date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-339752-o6atz33c.txt cache: ./cache/cord-339752-o6atz33c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-339752-o6atz33c.txt' === file2bib.sh === id: cord-323995-cpn34j02 author: Chen, Jun title: Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response date: 2017-12-01 pages: extension: .txt txt: ./txt/cord-323995-cpn34j02.txt cache: ./cache/cord-323995-cpn34j02.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-323995-cpn34j02.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-326614-cik3ino6 author: Corder, Brigette N. title: A Decade in Review: A Systematic Review of Universal Influenza Vaccines in Clinical Trials during the 2010 Decade date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-326614-cik3ino6.txt cache: ./cache/cord-326614-cik3ino6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-326614-cik3ino6.txt' === file2bib.sh === id: cord-317587-rrx2r4n2 author: Fan, Wensheng title: Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure date: 2019-09-26 pages: extension: .txt txt: ./txt/cord-317587-rrx2r4n2.txt cache: ./cache/cord-317587-rrx2r4n2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-317587-rrx2r4n2.txt' === file2bib.sh === id: cord-313439-cadyykks author: Felten, Sandra title: Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature date: 2019-11-15 pages: extension: .txt txt: ./txt/cord-313439-cadyykks.txt cache: ./cache/cord-313439-cadyykks.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 3 resourceName b'cord-313439-cadyykks.txt' === file2bib.sh === id: cord-335614-qh98622y author: Xu, Puzhi title: A Multi-Omics Study of Chicken Infected by Nephropathogenic Infectious Bronchitis Virus date: 2019-11-16 pages: extension: .txt txt: ./txt/cord-335614-qh98622y.txt cache: ./cache/cord-335614-qh98622y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-335614-qh98622y.txt' === file2bib.sh === id: cord-337707-xbwilp1w author: Kin, Nathalie title: Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes date: 2015-05-07 pages: extension: .txt txt: ./txt/cord-337707-xbwilp1w.txt cache: ./cache/cord-337707-xbwilp1w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-337707-xbwilp1w.txt' === file2bib.sh === id: cord-342130-eo4le4v3 author: Qin, Pan title: Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy date: 2019-05-18 pages: extension: .txt txt: ./txt/cord-342130-eo4le4v3.txt cache: ./cache/cord-342130-eo4le4v3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-342130-eo4le4v3.txt' === file2bib.sh === id: cord-342923-prgorr3d author: Li, Zhonghua title: Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication date: 2018-03-13 pages: extension: .txt txt: ./txt/cord-342923-prgorr3d.txt cache: ./cache/cord-342923-prgorr3d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-342923-prgorr3d.txt' === file2bib.sh === id: cord-317037-1qydcc5e author: Kumar, Asit title: Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-317037-1qydcc5e.txt cache: ./cache/cord-317037-1qydcc5e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-317037-1qydcc5e.txt' === file2bib.sh === id: cord-334027-xhfmio7k author: Fagre, Anna C. title: Can Bats Serve as Reservoirs for Arboviruses? date: 2019-03-03 pages: extension: .txt txt: ./txt/cord-334027-xhfmio7k.txt cache: ./cache/cord-334027-xhfmio7k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-334027-xhfmio7k.txt' === file2bib.sh === id: cord-341138-mxjsp3cm author: Denner, Joachim title: Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV) date: 2016-12-20 pages: extension: .txt txt: ./txt/cord-341138-mxjsp3cm.txt cache: ./cache/cord-341138-mxjsp3cm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-341138-mxjsp3cm.txt' === file2bib.sh === id: cord-335567-ssnvr6nj author: Berry, Michael title: Identification of New Respiratory Viruses in the New Millennium date: 2015-03-06 pages: extension: .txt txt: ./txt/cord-335567-ssnvr6nj.txt cache: ./cache/cord-335567-ssnvr6nj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-335567-ssnvr6nj.txt' === file2bib.sh === id: cord-321013-8pkrg0mx author: McBride, Ruth title: The Coronavirus Nucleocapsid Is a Multifunctional Protein date: 2014-08-07 pages: extension: .txt txt: ./txt/cord-321013-8pkrg0mx.txt cache: ./cache/cord-321013-8pkrg0mx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-321013-8pkrg0mx.txt' === file2bib.sh === id: cord-347362-e4paw26n author: Klein-Richers, Ute title: Prevalence of Feline Coronavirus Shedding in German Catteries and Associated Risk Factors date: 2020-09-08 pages: extension: .txt txt: ./txt/cord-347362-e4paw26n.txt cache: ./cache/cord-347362-e4paw26n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-347362-e4paw26n.txt' === file2bib.sh === id: cord-336536-ie5ok0lz author: Yeh, Ming Te title: Mapping Attenuation Determinants in Enterovirus-D68 date: 2020-08-08 pages: extension: .txt txt: ./txt/cord-336536-ie5ok0lz.txt cache: ./cache/cord-336536-ie5ok0lz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-336536-ie5ok0lz.txt' === file2bib.sh === id: cord-345651-admlzeu4 author: Wang, Gang title: The N-Terminal Domain of Spike Protein Is Not the Enteric Tropism Determinant for Transmissible Gastroenteritis Virus in Piglets date: 2019-03-30 pages: extension: .txt txt: ./txt/cord-345651-admlzeu4.txt cache: ./cache/cord-345651-admlzeu4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-345651-admlzeu4.txt' === file2bib.sh === id: cord-338973-73a7uvyz author: Xu, Jiabao title: Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV date: 2020-02-22 pages: extension: .txt txt: ./txt/cord-338973-73a7uvyz.txt cache: ./cache/cord-338973-73a7uvyz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-338973-73a7uvyz.txt' === file2bib.sh === id: cord-338811-2bi2edcw author: Lennemann, Nicholas J. title: Imaging-Based Reporter Systems to Define CVB-Induced Membrane Remodeling in Living Cells date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-338811-2bi2edcw.txt cache: ./cache/cord-338811-2bi2edcw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-338811-2bi2edcw.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 3 resourceName b'cord-314505-7qh8dsew.txt' === file2bib.sh === id: cord-349560-8n65rgfz author: Kleines, Michael title: WU Polyomavirus (WUPyV): A Recently Detected Virus Causing Respiratory Disease? date: 2009-11-04 pages: extension: .txt txt: ./txt/cord-349560-8n65rgfz.txt cache: ./cache/cord-349560-8n65rgfz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-349560-8n65rgfz.txt' === file2bib.sh === id: cord-338436-0z828org author: Tzou, Philip L. title: Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-338436-0z828org.txt cache: ./cache/cord-338436-0z828org.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-338436-0z828org.txt' === file2bib.sh === id: cord-351760-698voi9y author: Han, Hui-Ju title: Neutralizing Monoclonal Antibodies as Promising Therapeutics against Middle East Respiratory Syndrome Coronavirus Infection date: 2018-11-30 pages: extension: .txt txt: ./txt/cord-351760-698voi9y.txt cache: ./cache/cord-351760-698voi9y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-351760-698voi9y.txt' === file2bib.sh === id: cord-341968-uc8i9h0m author: Izaguirre, Gonzalo title: The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases date: 2019-09-09 pages: extension: .txt txt: ./txt/cord-341968-uc8i9h0m.txt cache: ./cache/cord-341968-uc8i9h0m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-341968-uc8i9h0m.txt' === file2bib.sh === id: cord-352619-s2x53grh author: Payne, Natalie title: Novel Circoviruses Detected in Feces of Sonoran Felids date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-352619-s2x53grh.txt cache: ./cache/cord-352619-s2x53grh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-352619-s2x53grh.txt' === file2bib.sh === id: cord-351228-hpo8bboi author: Wasilenko, Shawn T. title: Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis? date: 2013-01-24 pages: extension: .txt txt: ./txt/cord-351228-hpo8bboi.txt cache: ./cache/cord-351228-hpo8bboi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-351228-hpo8bboi.txt' === file2bib.sh === id: cord-348968-0yoq0geu author: Zhang, Maodong title: Assessment of Metagenomic Sequencing and qPCR for Detection of Influenza D Virus in Bovine Respiratory Tract Samples date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-348968-0yoq0geu.txt cache: ./cache/cord-348968-0yoq0geu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-348968-0yoq0geu.txt' === file2bib.sh === id: cord-353365-ujz5nkk3 author: Pirnay, Jean-Paul title: Study of a SARS-CoV-2 Outbreak in a Belgian Military Education and Training Center in Maradi, Niger date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-353365-ujz5nkk3.txt cache: ./cache/cord-353365-ujz5nkk3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-353365-ujz5nkk3.txt' === file2bib.sh === id: cord-342739-iy9vjpuh author: Schwartz, David A. title: Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections date: 2020-02-10 pages: extension: .txt txt: ./txt/cord-342739-iy9vjpuh.txt cache: ./cache/cord-342739-iy9vjpuh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-342739-iy9vjpuh.txt' === file2bib.sh === id: cord-350964-0jtfc271 author: Van Nguyen, Dung title: Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam date: 2018-02-28 pages: extension: .txt txt: ./txt/cord-350964-0jtfc271.txt cache: ./cache/cord-350964-0jtfc271.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-350964-0jtfc271.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 4 resourceName b'cord-351489-tzmev77c.txt' === file2bib.sh === id: cord-354738-4rxradwz author: Kohl, Claudia title: European Bats as Carriers of Viruses with Zoonotic Potential date: 2014-08-13 pages: extension: .txt txt: ./txt/cord-354738-4rxradwz.txt cache: ./cache/cord-354738-4rxradwz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-354738-4rxradwz.txt' === file2bib.sh === id: cord-349117-xfir3m5p author: Hyseni, Inesa title: Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-349117-xfir3m5p.txt cache: ./cache/cord-349117-xfir3m5p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-349117-xfir3m5p.txt' === file2bib.sh === id: cord-345472-qrddwebe author: Sebina, Ismail title: The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-345472-qrddwebe.txt cache: ./cache/cord-345472-qrddwebe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-345472-qrddwebe.txt' === file2bib.sh === id: cord-338589-1ent68fx author: Stoddard, Shana V. title: Optimization Rules for SARS-CoV-2 M(pro) Antivirals: Ensemble Docking and Exploration of the Coronavirus Protease Active Site date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-338589-1ent68fx.txt cache: ./cache/cord-338589-1ent68fx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-338589-1ent68fx.txt' === file2bib.sh === id: cord-347053-m5m4zgfy author: Pharo, Elizabeth A. title: Host–Pathogen Responses to Pandemic Influenza H1N1pdm09 in a Human Respiratory Airway Model date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-347053-m5m4zgfy.txt cache: ./cache/cord-347053-m5m4zgfy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-347053-m5m4zgfy.txt' === file2bib.sh === id: cord-353609-no3mbg5d author: Vandegrift, Kurt J. title: An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses date: 2011-04-15 pages: extension: .txt txt: ./txt/cord-353609-no3mbg5d.txt cache: ./cache/cord-353609-no3mbg5d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-353609-no3mbg5d.txt' === file2bib.sh === id: cord-351377-xorj8tnz author: Kao, Chi-Fei title: The Characterization of Immunoprotection Induced by a cDNA Clone Derived from the Attenuated Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strain date: 2018-10-04 pages: extension: .txt txt: ./txt/cord-351377-xorj8tnz.txt cache: ./cache/cord-351377-xorj8tnz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-351377-xorj8tnz.txt' === file2bib.sh === id: cord-352527-eeyqh9nc author: Zhou, Yusen title: Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain date: 2019-01-14 pages: extension: .txt txt: ./txt/cord-352527-eeyqh9nc.txt cache: ./cache/cord-352527-eeyqh9nc.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 3 resourceName b'cord-352527-eeyqh9nc.txt' === file2bib.sh === id: cord-352007-3djwbivp author: Xiang, Qi title: Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-352007-3djwbivp.txt cache: ./cache/cord-352007-3djwbivp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-352007-3djwbivp.txt' === file2bib.sh === id: cord-349011-kxhpdvri author: Grandvaux, Nathalie title: CSV2018: The 2nd Symposium of the Canadian Society for Virology date: 2019-01-18 pages: extension: .txt txt: ./txt/cord-349011-kxhpdvri.txt cache: ./cache/cord-349011-kxhpdvri.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-349011-kxhpdvri.txt' === file2bib.sh === id: cord-351955-9l4786lb author: Pedersen, Niels C. title: Significance of Coronavirus Mutants in Feces and Diseased Tissues of Cats Suffering from Feline Infectious Peritonitis date: 2009-08-26 pages: extension: .txt txt: ./txt/cord-351955-9l4786lb.txt cache: ./cache/cord-351955-9l4786lb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-351955-9l4786lb.txt' === file2bib.sh === id: cord-351365-dc9t3vh3 author: Todt, Daniel title: Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations date: 2016-10-13 pages: extension: .txt txt: ./txt/cord-351365-dc9t3vh3.txt cache: ./cache/cord-351365-dc9t3vh3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-351365-dc9t3vh3.txt' === file2bib.sh === id: cord-307046-ko3bdvo0 author: Vasilakis, Nikos title: Exploiting the Legacy of the Arbovirus Hunters date: 2019-05-23 pages: extension: .txt txt: ./txt/cord-307046-ko3bdvo0.txt cache: ./cache/cord-307046-ko3bdvo0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-307046-ko3bdvo0.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 4 resourceName b'cord-346836-6jyv0q5e.txt' === file2bib.sh === id: cord-343690-rafvxgx1 author: Hartmann, Katrin title: Clinical Aspects of Feline Retroviruses: A Review date: 2012-10-31 pages: extension: .txt txt: ./txt/cord-343690-rafvxgx1.txt cache: ./cache/cord-343690-rafvxgx1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-343690-rafvxgx1.txt' === file2bib.sh === id: cord-354068-4qlk6y7h author: Friedrich, Brian M. title: Potential Vaccines and Post-Exposure Treatments for Filovirus Infections date: 2012-09-21 pages: extension: .txt txt: ./txt/cord-354068-4qlk6y7h.txt cache: ./cache/cord-354068-4qlk6y7h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-354068-4qlk6y7h.txt' Que is empty; done journal-viruses-cord === reduce.pl bib === id = cord-002590-24o2viv3 author = Rahe, Michael C. title = Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus date = 2017-06-13 pages = extension = .txt mime = text/plain words = 8016 sentences = 375 flesch = 34 summary = Pig immune response to general stimulus and to porcine reproductive and respiratory syndrome virus infection: A meta-analysis approach Antigen-specific B-cell responses to porcine reproductive and respiratory syndrome virus infection The Chinese highly pathogenic porcine reproductive and respiratory syndrome virus infection suppresses Th17 cells response in vivo Pathogenic and humoral immune responses to porcine reproductive and respiratory syndrome virus (PRRSV) are related to viral load in acute infection Porcine reproductive and respiratory syndrome virus-infected alveolar macrophages contain no detectable levels of viral proteins in their plasma membrane and are protected against antibody-dependent, complement-mediated cell lysis Polyclonal activation of B cells occurs in lymphoid organs from porcine reproductive and respiratory syndrome virus (PRRSV)-infected pigs The role of porcine reproductive and respiratory syndrome virus infection in immune phenotype and Th1/Th2 balance of dendritic cells Porcine reproductive and respiratory syndrome virus induces pronounced immune modulatory responses at mucosal tissues in the parental vaccine strain VR2332 infected pigs cache = ./cache/cord-002590-24o2viv3.txt txt = ./txt/cord-002590-24o2viv3.txt === reduce.pl bib === id = cord-002994-1zjrunzc author = Faye, Martin title = Full-Genome Characterization and Genetic Evolution of West African Isolates of Bagaza Virus date = 2018-04-13 pages = extension = .txt mime = text/plain words = 11495 sentences = 517 flesch = 45 summary = Based on these alignments, we investigated the genetic properties of these different isolates circulating in West Africa, such as genome length and location of main conserved amino acid motifs previously described in mosquito-borne flaviviruses (MBFVs) with sometimes mutations which include no physicochemical properties changes [3] . The RNAz method [21] implemented in the Vienna RNA Websuite (http://rna.tbi.univie.ac.at/) [22] was used to detect thermodynamically stable and evolutionarily conserved structural RNA domains on complete non-coding regions of the 11 West African BAGV isolates characterized in this study and the isolates from Spain and CAR, because complete non-coding sequences are not currently available for the isolate from India. Here, we described location of main conserved amino acid motifs on BAGV proteins using in silico analysis of complete genome sequences of the 11 West African BAGV isolates characterized in this study and sequences from India, CAR and Spain. cache = ./cache/cord-002994-1zjrunzc.txt txt = ./txt/cord-002994-1zjrunzc.txt === reduce.pl bib === id = cord-002076-7t4d4vvo author = Li, Yongfeng title = Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology date = 2016-05-06 pages = extension = .txt mime = text/plain words = 4996 sentences = 229 flesch = 36 summary = Commonly used tests based on wild-type viruses, such as immunostaining, cannot meet the demands for rapid detection of viral replication, high-throughput screening for antivirals, as well as for tracking viral proteins or virus transport in real time. This article reviews the applications of RCREVs in diagnostic and molecular virology, including rapid neutralization tests, high-throughput screening systems, identification of viral receptors and virus-host interactions, dynamics of viral infections in vitro and in vivo, vaccination approaches and others. Replicating-competent reporter-expressing viruses (RCREVs) are one type of artificially modified viruses that not only retain the viral genetic characteristics but also possess the new properties of the reporter genes, which represent a useful tool for quantitative analysis of viral replication and tracking viral protein transport in both living cells and animals. cache = ./cache/cord-002076-7t4d4vvo.txt txt = ./txt/cord-002076-7t4d4vvo.txt === reduce.pl bib === id = cord-001972-1zisomq5 author = Wang, Xue title = Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells date = 2016-02-02 pages = extension = .txt mime = text/plain words = 3921 sentences = 197 flesch = 46 summary = These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways. Cells treated with pH1N1 had higher level of NF-kB phosphorylation and increased protein expression of NFAT and AP-1 ( Figure 3B ) relative to HIV-1 infection alone, suggesting pH1N1 infection can activate host transcription factors required for HIV-1 replication in Jurkat cells. These data indicate that pandemic influenza A (H1N1) infection can increase accumulation of CD4 protein and induce T cell signaling and activate host transcription factors required for HIV-1 replication. In conclusion, our results demonstrate that pandemic influenza A (H1N1) virus infection can induce cell death through apoptotic signaling pathways and promote HIV-1 replication through the MAPK and TCR-related signaling pathways in HIV-1-infected Jurkat cells. Pandemic influenza A (H1N1) virus infection is also able to reactivate HIV-1 replication from its state of latent infection through activating apoptosis and TCR-signaling pathways. cache = ./cache/cord-001972-1zisomq5.txt txt = ./txt/cord-001972-1zisomq5.txt === reduce.pl bib === id = cord-000808-pxryt8wn author = Leroy, Eric title = Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa date = 2012-09-13 pages = extension = .txt mime = text/plain words = 2871 sentences = 133 flesch = 38 summary = Since the reemergence of Ebola virus in Central Africa, the CIRMF "Emerging Viral Disease Unit" developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the National Public Health System and the World Health Organization to epidemics of Ebola virus disease. As a National reference laboratory, CIRMF has the following roles: diagnosis of suspected cases during outbreaks of viral hemorrhagic fevers or severe clinical infectious syndromes; development of new methods for diagnosing such infections; surveillance of animal fatalities in reservoir or intermediate hosts; and intervention during outbreaks of unknown etiology. The Emerging Viral Diseases Unit, CIRMF, proposes forming a research partnership to study infectious diseases transmitted by animals of the tropical rain forests regions of Equatorial Africa. cache = ./cache/cord-000808-pxryt8wn.txt txt = ./txt/cord-000808-pxryt8wn.txt === reduce.pl bib === id = cord-003453-p2buyrcj author = Batista, Mariana N. title = Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus date = 2019-01-11 pages = extension = .txt mime = text/plain words = 4157 sentences = 220 flesch = 49 summary = In this study, we tested the activity of the natural compounds berberine and emodin for their ability to inhibit ZIKV infection. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. cache = ./cache/cord-003453-p2buyrcj.txt txt = ./txt/cord-003453-p2buyrcj.txt === reduce.pl bib === id = cord-000804-0hlj6r10 author = Brauburger, Kristina title = Forty-Five Years of Marburg Virus Research date = 2012-10-01 pages = extension = .txt mime = text/plain words = 14922 sentences = 730 flesch = 45 summary = While the ectodomain, which is mainly formed by GP 1 , mediates binding to entry factors and receptors [87] [88] [89] [90] [91] [92] [93] [94] [95] , the transmembrane subunit GP 2 contains the fusion peptide and is presumed to mediate fusion of the viral and the cellular membrane based on similarity to EBOV GP 2 both at the amino acid and structural level [96, 97] . The IFN-inducible antiviral protein tetherin was shown to block the release of VP40-induced virus-like MARV and EBOV particles, suggesting that tetherin might act as a restriction factor for filovirus release [102, 103] . After the nucleocapsid is released into the cytoplasm of the infected cell, transcription and replication of the viral RNA genome takes place (Figure 7 ). Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections cache = ./cache/cord-000804-0hlj6r10.txt txt = ./txt/cord-000804-0hlj6r10.txt === reduce.pl bib === id = cord-002561-7j43yic1 author = Donato, Celeste title = The Broad Host Range and Genetic Diversity of Mammalian and Avian Astroviruses date = 2017-05-10 pages = extension = .txt mime = text/plain words = 7434 sentences = 327 flesch = 35 summary = Astroviruses within the Mamastrovirus genus are derived from numerous mammalian species in addition to humans (HAstV), including farmed species such as pigs (PAstV), sheep (OAstV), cattle (BoAstV), domesticated animals including cats (FAstV), and dogs (CaAstV), rodents and small mammals including mink (MiAstV), bats (BAstV), rats (RAstV), mice, rabbit (RabAstV), fox, marmot (HHMastV), porcupine, shrew, vole, and larger species including deer (CcAstV), monkeys, water buffalo (BufAstV), yak, camel (DcAstV), and cheetah (ChAstV) (Figure 1a,b) . Viruses from the Avastrovirus genus have been characterized from numerous farmed avian species including turkeys (TAstV), ducks (DAstV), chicken (CAstV), guineafowl (GFAstV), pigeon (PiAstV), goose, as well as wild aquatic and terrestrial birds including heron, doves, penguins, and many other species (Figure 2a) . Astrovirus strains identified from fecal samples of multiple non-human primate species from wild, captive, and peri-urban environments in Bangladesh and Cambodia reveal multiple interspecies transmission events, with viruses closely related to the VA/HMO lineage of human viruses, and non-human mammalian and avian astroviruses (Figure 1a,b) [28] . cache = ./cache/cord-002561-7j43yic1.txt txt = ./txt/cord-002561-7j43yic1.txt === reduce.pl bib === id = cord-002589-xq3iq8ai author = Frossard, Jean-Pierre title = UK Pigs at the Time of Slaughter: Investigation into the Correlation of Infection with PRRSV and HEV date = 2017-06-09 pages = extension = .txt mime = text/plain words = 3767 sentences = 162 flesch = 48 summary = To follow up these studies, we report here on (1) the investigation of PRRSV active infection (RNA in tonsil) using the same 2013 abattoir survey sample-set and (2) an analysis of the correlation of PRRSV and HEV infection in these pigs, which could be of significance for the control of both diseases and in informing farming practices for reducing HEV in the food chain. The phylogenetic trees (Figure 1 ) illustrate the genetic diversity of the ORF5 genes from the 23 samples in this study in comparison to the vaccine virus licensed in the UK at the time and 48 published reference sequences representing the different genotypes and subtypes ( Figure 1A ) and in more detail, in the context of 431 previously sequenced viruses specifically from UK pigs between 1991 and 2014 (unpublished data) ( Figure 1B ). cache = ./cache/cord-002589-xq3iq8ai.txt txt = ./txt/cord-002589-xq3iq8ai.txt === reduce.pl bib === id = cord-002691-synm1cyw author = Hou, Jiun-Nan title = PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication date = 2017-09-20 pages = extension = .txt mime = text/plain words = 9842 sentences = 477 flesch = 51 summary = title: PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication Results revealed that the TOR signaling pathway may have retained its activity involved in controlling cap-dependent protein translation in C6/36 cells infected by the DENV2. Results revealed that the TOR signaling pathway may have retained its activity involved in controlling cap-dependent protein translation in C6/36 cells infected by the DENV2. This suggested that the PERK signaling pathway is involved in regulating cellular protein translation when ER stress is induced by DENV2 in mosquito cells. This suggested that the PERK signaling pathway is involved in regulating cellular protein translation when ER stress is induced by DENV2 in mosquito cells. In the meantime, PERK inhibition in this study was further shown to increase MMP changes and ROS accumulation, indicating that DENV2-induced ER stress may be reduced by activating the PERK signal pathway since such cellular responses were not evidently shown in uninfected PERKi-treated cells (Figures S1-S3) . cache = ./cache/cord-002691-synm1cyw.txt txt = ./txt/cord-002691-synm1cyw.txt === reduce.pl bib === id = cord-003334-ion97n4b author = De Silva Senapathi, Upasama title = The In Ovo Delivery of CpG Oligonucleotides Protects against Infectious Bronchitis with the Recruitment of Immune Cells into the Respiratory Tract of Chickens date = 2018-11-15 pages = extension = .txt mime = text/plain words = 5827 sentences = 266 flesch = 54 summary = Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown. We found significantly higher survival rates and reduced IBV infection in the chickens following the pre-treatment of the ED 18 eggs with CpG ODNs. At 3 days post infection (dpi), we found an increased recruitment of macrophages, cluster of differentiation (CD)8α+ and CD4+ T lymphocytes, and an up-regulation of interferon (IFN)-γ mRNA in the respiratory tract of the chickens. Considering that we observed a significant reduction in the IBV induced morbidity and mortality of in ovo CpG ODN pre-treated birds correlating with varying degrees of increased macrophages, CD4+, and CD8α+ T cells in the tracheal and lung tissues, we needed to further elucidate the mechanisms by which these immune cells were efficiently recruited. cache = ./cache/cord-003334-ion97n4b.txt txt = ./txt/cord-003334-ion97n4b.txt === reduce.pl bib === id = cord-003284-hjx2d5rq author = Márquez-Jurado, Silvia title = An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo date = 2018-10-07 pages = extension = .txt mime = text/plain words = 9917 sentences = 409 flesch = 51 summary = Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. To analyze the genetic stability of the recombinant ZIKV harboring the point mutation A175V in the coding region of the NS2A protein (rZIKV-RGN-mNS2A), total RNA was purified from Vero cells infected with viruses from passage 1 (P1) to passage 5 (P5) using the RNeasy minikit (Qiagen), according to the manufacturer's specifications. To investigate whether the reduced RNA synthesis of rZIKV-RGN-mNS2A in Vero cells could result in viral attenuation in vivo, the ability of the mutant virus to induce pathogenesis was analyzed in A129 mice and compared with that of the parental rZIKV-RGN ( Figure 6 ). cache = ./cache/cord-003284-hjx2d5rq.txt txt = ./txt/cord-003284-hjx2d5rq.txt === reduce.pl bib === id = cord-003407-f5v3hhr8 author = Hung, Ting-Chun title = Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection date = 2018-11-27 pages = extension = .txt mime = text/plain words = 4790 sentences = 203 flesch = 41 summary = Thus, RC's anti-HCV activity appeared strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. Viruses 2018, 10, x FOR PEER REVIEW 6 of 12 strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. To further characterize the mechanism(s) underlying RC's anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry. To further characterize the mechanism(s) underlying RC's anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry. cache = ./cache/cord-003407-f5v3hhr8.txt txt = ./txt/cord-003407-f5v3hhr8.txt === reduce.pl bib === id = cord-003516-l1lq8yga author = Zhang, Jing title = A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations date = 2019-01-31 pages = extension = .txt mime = text/plain words = 2357 sentences = 133 flesch = 38 summary = title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations A signature of these "old" HAdV-E4 is the absence of a critical replication motif, NF-I, which is found in all HAdV respiratory pathogens and most HAdVs. However, our recent survey of flu-like disease in children in Hong Kong reveals that the emergent HAdV-E4 pathogens circulating in civilian populations contain NF-I, indicating recombination and reflecting host-adaptation that enables the "new" HAdV-E4 to replicate more efficiently in human cells and foretells more potential HAdV-E4 outbreaks in immune-naïve civilian populations. Recent isolates are recombinants containing this HAdV replication motif [1] , presumably permitting an expansion of the virus range into the immune-naïve populations [5] [6] [7] [21] [22] [23] , and should be noted as a molecular evolution example of a post-zoonotic, host-adaptation of a "novel" and "emergent" human pathogen. cache = ./cache/cord-003516-l1lq8yga.txt txt = ./txt/cord-003516-l1lq8yga.txt === reduce.pl bib === id = cord-003646-kjkuet78 author = López-Camacho, César title = Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus date = 2019-04-03 pages = extension = .txt mime = text/plain words = 6359 sentences = 314 flesch = 49 summary = We have designed viral-vectored vaccines to express the structural proteins of CHIKV, using the replication-deficient chimpanzee adenoviral platform, ChAdOx1. Our vaccines induce high frequencies of anti-chikungunya specific T-cell responses as well as high titres of anti-CHIKV E2 antibodies with high capacity for in vitro neutralisation. In mice, ChAdOx1 vaccines candidates expressing sCHIKV antigens are able to induce strong humoral and cellular responses upon a single and non-adjuvanted immunisation approach. Finally, whilst durability of humoral responses was achieved upon a single immunisation, MVA vaccines expressing sCHIKV were produced to be used as an alternative heterologous booster regime (ChAdOx1/MVA), in order to increase neutralising antibody titres. In addition, a western blot was performed using a monoclonal antibody against CHIKV E1 (Figure 3d ); we detected a specific band in the positive control E1 protein (lane 9), as well as a 55 kDa band in all the supernatant fractions from both ChAdOx1 sCHIKV-and ChAdOx1 sCHIKV ∆C-transduced cells. cache = ./cache/cord-003646-kjkuet78.txt txt = ./txt/cord-003646-kjkuet78.txt === reduce.pl bib === id = cord-003775-1axsebya author = Lelli, Davide title = Hypsugopoxvirus: A Novel Poxvirus Isolated from Hypsugo savii in Italy date = 2019-06-19 pages = extension = .txt mime = text/plain words = 3010 sentences = 152 flesch = 45 summary = Herein, we report the isolation, nearly complete genome sequencing, and annotation of a novel poxvirus detected from an insectivorous bat (Hypsugo savii) in Northern Italy. In this study, we report the isolation, nearly complete genomic sequencing, and annotation of a novel poxvirus detected from an insectivorous bat (Hypsugo savii) in Northern Italy. Phylogenetic analyses suggest that HYPV belongs to the Chordopoxvirinae subfamily, revealing the highest similarity (85%) with Eptesipoxvirus (EPTV) detected from the microbat Eptesicus fuscus in WA, USA in 2011, which is associated with bat necrosuppurative osteomyelitis in multiple joints. For the nearly complete viral genome sequencing, BLAST analysis revealed the highest nucleotide identity (85%) to the Eptesipoxvirus (EPTV) strain "Washington", a member of the Chordopoxvirinae subfamily identified in microbats in the USA ( Table 2 ). To conclude, a new poxvirus, HYPV, was detected in bats in Europe and its viral ecology and disease associations should be investigated further. cache = ./cache/cord-003775-1axsebya.txt txt = ./txt/cord-003775-1axsebya.txt === reduce.pl bib === id = cord-003761-ikni2acz author = Li, Zengbin title = Biological Function and Application of Picornaviral 2B Protein: A New Target for Antiviral Drug Development date = 2019-06-04 pages = extension = .txt mime = text/plain words = 6425 sentences = 331 flesch = 39 summary = In this review, we mainly summarize recent research data on the viroporin or viroporin-like activity of 2B proteins, which affects the biological function of the membrane, regulates cell death, and affects the host immune response. In particular, the 2B protein may change the Ca 2+ concentration to regulate autophagy and apoptosiswhich are distinct cell death mechanisms controlled by the virus to effectively evade the host immunity, thereby promoting viral replication and release [48] [49] [50] [51] [52] . Thus, the main points of focus for research on the structure and function of the 2B protein toward ultimate drug development are: (1) mechanism of increasing membrane permeability to disturb the ion balance, (2) regulation of autophagy and apoptosis, (3) inhibition of the host immune response, and (4) promotion of viral replication and release. cache = ./cache/cord-003761-ikni2acz.txt txt = ./txt/cord-003761-ikni2acz.txt === reduce.pl bib === === reduce.pl bib === id = cord-001974-wjf3c7a7 author = Friis-Nielsen, Jens title = Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers date = 2016-02-19 pages = extension = .txt mime = text/plain words = 5773 sentences = 348 flesch = 48 summary = Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. The datasets went through a sequential pipeline with modules (in order) of preprocessing, computational subtraction of host sequences, low-complexity sequence removal, sequence assembly, clustering, association to metadata features, and taxonomical annotation. Associations from the shortest mode tended to have higher dispersion in the range of ORs. Furthermore, one block of clustering results using global alignment mode, alignment length based on the shortest contig, and a minimum sequence identity of 90% (c09ˆaSyG1), had an overall high range of ORs as well as the highest minimum values. The clusters are significantly associated with lowest p-values to biological features and the species annotations are described by HMP. cache = ./cache/cord-001974-wjf3c7a7.txt txt = ./txt/cord-001974-wjf3c7a7.txt === reduce.pl bib === id = cord-002808-84np9brx author = Campos, Samuel K. title = Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2 date = 2017-12-03 pages = extension = .txt mime = text/plain words = 9673 sentences = 460 flesch = 43 summary = How does L2, the minor capsid protein from a non-enveloped virus, complexed with the vDNA within the lumen of intracellular vesicular compartments, interact with a variety of cytosolic sorting molecules to direct its own transport to the TGN? Given the requirement for furin in TGN localization of L2/vDNA, it is very likely that cleavage triggers a structural change that enables L2 to insert and protrude into the local membrane via the TMD to recruit cytosolic SNXs and retromer. Regardless of the precise mechanisms of L2 translocation, the minor capsid protein eventually leaves vesicular compartments and is seen along with vDNA within interphase nuclei of infected cells, localized to punctate nuclear foci called promyelocytic leukemia (PML) nuclear domains, also known as PML oncogenic domains (PODS), or ND10 bodies [108] . The L2 minor capsid protein of low-risk human papillomavirus type 11 interacts with host nuclear import receptors and viral DNA Direct binding of retromer to human papillomavirus type 16 minor capsid protein L2 mediates endosome exit during viral infection cache = ./cache/cord-002808-84np9brx.txt txt = ./txt/cord-002808-84np9brx.txt === reduce.pl bib === id = cord-003130-p2h8p5bm author = Lindqvist, Richard title = Tick-Borne Flaviviruses and the Type I Interferon Response date = 2018-06-21 pages = extension = .txt mime = text/plain words = 8350 sentences = 481 flesch = 48 summary = There are more than 70 viruses in the genus flavivirus, and they are transmitted by arthropods such as mosquitoes (dengue virus (DENV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), yellow fever virus (YFV), and Zika virus (ZIKV) and ticks (tick-borne encephalitis virus (TBEV), Langat virus (LGTV), Kyasanur forest disease virus (KFDV), Omsk hemorrhagic fever virus (OHFV), Powassan virus (POWV), and Louping-ill virus (LIV)) [1] [2] [3] [4] [5] . Two other ISGs which have been shown to be antivirally active against TBEV are virus inhibitory protein endoplasmic reticulum associated interferon inducible (viperin) and tripartite motif-79α (TRIM79α). The role of interferon in tick-borne encephalitis virus-infected l cells. A functional toll-like receptor 3 gene (tlr3) may be a risk factor for tick-borne encephalitis virus (tbev) infection Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection cache = ./cache/cord-003130-p2h8p5bm.txt txt = ./txt/cord-003130-p2h8p5bm.txt === reduce.pl bib === id = cord-002185-oz7hras7 author = Nelson, Elizabeth A. title = Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications date = 2016-08-02 pages = extension = .txt mime = text/plain words = 5047 sentences = 249 flesch = 52 summary = In this system, 4-hydroxy-zuclomiphene appeared more potent than the Our previous findings indicated that clomiphene blocks EBOV infection by blocking entry of viral particles into the cell cytoplasm [20, 29] ; this effect appears to be at the level of fusion between the membrane of the viral particle and the limiting membrane of an Niemann-Pick disease, type C1 positive (NPC1 + ) endolysosome, the site of EBOV fusion [30] [31] [32] . Similar results were seen when comparing eight doses of clomiphene and zuclomiphene in trVLP infection ( Figure 5A ) and VLP entry ( Figure 5B ) assays. Where tested, they were equally effective to each other in two cell types and for entry mediated by three filoviral GPs. 4-hydroxy-enclomiphene, and 4-hydroxy-zuclomiphene also blocked EBOV trVLP infection and VLP entry under the cache = ./cache/cord-002185-oz7hras7.txt txt = ./txt/cord-002185-oz7hras7.txt === reduce.pl bib === id = cord-003586-afnto2tz author = Baillet, Nicolas title = Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses date = 2019-03-23 pages = extension = .txt mime = text/plain words = 7588 sentences = 380 flesch = 51 summary = We identified host cellular proteins that interact with Z proteins of both viruses by using a high throughput yeast two-hybrid (HT-Y2H) screening protocol in which AH109 yeast cells were transformed with a Y2H vector encoding the Z protein of LASV or MOPV fused to the GAL4-BD domain (viral bait). Y2H screens allowed us to identify, among others, two known autophagy adaptors, namely NDP52 and TAX1BP1, which have been shown to interact with the Z protein of MOPV, but not LASV (Table 1) . Overall, these results suggest that NDP52 and TAX1BP1 are not involved in the production of infectious virus for either MOPV or LASV in HeLa cells. These results were unexpected and suggest that autophagy adaptors could play a role during LASV or MOPV infection that does not affect the viral fitness in the cell lines we used. cache = ./cache/cord-003586-afnto2tz.txt txt = ./txt/cord-003586-afnto2tz.txt === reduce.pl bib === id = cord-003865-24lz9tf1 author = Zhou, Hongzhuan title = Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells date = 2019-08-13 pages = extension = .txt mime = text/plain words = 5582 sentences = 281 flesch = 50 summary = To evaluate the antiviral effects of the three drugs of Nitazoxanide, Closantel Sodium and Closantel, F81 cells were seeded in 6-well plates at 7.5 × 10 5 cells per well and pretreated with the 3 drugs at a final concentrations of 5 µM, 10 µM, and 20 µM, respectively, for 1 h, then treated cells were infected with CPV at MOI of 0.076 as described above. As mentioned above, the identified drugs Nitazoxanide, Closantel Sodium, and Closantel can reduce the copy numbers of CPV viral DNA to 0.07%, 24.04%, and 20.83%, respectively, compared with the 0.1% DMSO-treated control ( Figure 3) . Our CPE-based screening assay showed that the percentage CPE inhibition of Oseltamivir and Cidofovir were 2.13 ± 2.41 and −1.28 ± 1.03 (Table S1 ), respectively, and that these two drugs had no anti-CPV effects on F81 cells. cache = ./cache/cord-003865-24lz9tf1.txt txt = ./txt/cord-003865-24lz9tf1.txt === reduce.pl bib === id = cord-003961-gs75ebo4 author = Yin, Xin title = Hepatitis E Virus Entry date = 2019-09-20 pages = extension = .txt mime = text/plain words = 5141 sentences = 261 flesch = 47 summary = The enteric route of transmission, EM evidence of naked virions in the feces, and the lack of coding capacity for envelope proteins all suggest that HEV is a nonenveloped virus. The enteric route of transmission, EM evidence of naked virions in the feces, and the lack of coding capacity for envelope proteins all suggest that HEV is a nonenveloped virus. However, recent studies show that the virus released from infected cells and circulating in the blood adopts a membrane associated, "quasienveloped" form, named "eHEV" [10, 11, 22] (Figure 1b ). However, recent studies show that the virus released from infected cells and circulating in the blood adopts a membrane associated, "quasienveloped" form, named "eHEV" [10, 11, 22] (Figure 1b ). The available evidence suggests that naked and quasienveloped HEV particles use different mechanisms for cell entry, and that entry of eHEV requires lysosomal degradation of the viral membrane. ORF3 protein of hepatitis E virus is essential for virion release from infected cells cache = ./cache/cord-003961-gs75ebo4.txt txt = ./txt/cord-003961-gs75ebo4.txt === reduce.pl bib === id = cord-001831-3aonqyub author = Royle, Jamie title = Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals? date = 2015-10-16 pages = extension = .txt mime = text/plain words = 6390 sentences = 311 flesch = 42 summary = Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention. Research over recent decades has identified a group of virus-encoded proteins able to mediate the passage of ions and solutes across cellular membranes, termed viroporins [1, 2] . Due to these broad perturbations to host cell physiology, it is not surprising that viroporin function has been shown to assist in all stages of the virus life cycle including entry, membrane penetration, genome replication and virus egress [1, 2] . This review will summarize our understanding of these putative viroporins, describe their known functions and attempt to highlight how possible ion channel activity may aid the life cycles of these small DNA tumor viruses. cache = ./cache/cord-001831-3aonqyub.txt txt = ./txt/cord-001831-3aonqyub.txt === reduce.pl bib === id = cord-003807-e2txo10z author = Ke, Fei title = Ranaviruses Bind Cells from Different Species through Interaction with Heparan Sulfate date = 2019-06-29 pages = extension = .txt mime = text/plain words = 5544 sentences = 300 flesch = 54 summary = Here, viral cell-binding proteins and their cognate cellular receptors were investigated using two ranaviruses, Andrias davidianus ranavirus (ADRV) and Rana grylio virus (RGV), and two different cell lines, Chinese giant salamander thymus cells (GSTC) and Epithelioma papulosum cyprinid (EPC) cells. Furthermore, recombinant viral envelope proteins ADRV-58L and RGV-53R bound heparin-Sepharose beads implying the potential that cell surface HS is involved in the initial interaction between ranaviruses and susceptible host cells. Rana grylio virus (RGV) and Andrias davidianus ranavirus (ADRV) are ranaviruses isolated from diseased pig frogs R. Furthermore, since ranavirus viral envelope proteins [38] [39] [40] [45] [46] [47] [48] are likely involved in the initial interaction between virus and host, we examined the ability of RGV-53R and its ADRV homolog, ADVR-58L, to bind heparin-Sepharose beads. The effect of heparin on virus infection was tested by monitoring viral plaque formation following incubation of ADRV and RGV in the presence of increasing concentrations of heparin. cache = ./cache/cord-003807-e2txo10z.txt txt = ./txt/cord-003807-e2txo10z.txt === reduce.pl bib === id = cord-004020-qtwcbn7m author = Gao, Yaning title = Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors date = 2019-11-02 pages = extension = .txt mime = text/plain words = 7693 sentences = 354 flesch = 50 summary = A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Gossypol-treated ZIKV was incubated with Vero E6 cells at 37 • C for 1 h in the presence of DMEM containing serial dilutions of each of the other three natural products identified, such as curcumin, digitonin, and conessine, or anti-ZIKV compound control (bortezomib). Based on Table 1 , four "hit" natural products, including gossypol, curcumin, digitonin, and conessine ( Figure 2A -D), were selected, since they demonstrated inhibitory activity against ZIKV infection with no obvious cytotoxicity in Vero E6 cells when observed under a microscope. Since gossypol demonstrated the highest antiviral activity individually against all ZIKV strains tested, we next investigated the potential combinatorial effects of the combination of gossypol with three other natural products identified, namely curcumin, digitonin, and conessine, as well as anti-ZIKV compound control (bortezomib). cache = ./cache/cord-004020-qtwcbn7m.txt txt = ./txt/cord-004020-qtwcbn7m.txt === reduce.pl bib === id = cord-003915-kje8lvgl author = Pigeyre, Laetitia title = Interaction of a Densovirus with Glycans of the Peritrophic Matrix Mediates Oral Infection of the Lepidopteran Pest Spodoptera frugiperda date = 2019-09-17 pages = extension = .txt mime = text/plain words = 9040 sentences = 462 flesch = 47 summary = As orally transmitted viruses, densoviruses, are also challenged by the complexity of the insect gut barriers, more specifically by the chitinous peritrophic matrix, that lines and protects the midgut epithelium; how capsids stick to and cross these barriers to reach their final cell destination where replication goes has been poorly studied in insects. In addition, we showed that JcDV early infection results in (i) an arrest of N-Acetylglucosamine (GlcNAc) secretion by epithelial cells associated with a disorganization of the PM structure mimicking the effect of chitin-binding plant lectin; (ii) substantial changes in the expression of gut genes, which may also contribute to an early gut dysfunction and participate to viral pathogenesis. Results presented here show that JcDV capsids display carbohydrate-binding properties that insure recognition of the peritrophic matrix and determines caterpillars oral infection. cache = ./cache/cord-003915-kje8lvgl.txt txt = ./txt/cord-003915-kje8lvgl.txt === reduce.pl bib === id = cord-003917-bswndfvk author = Lalle, Eleonora title = Pulmonary Involvement during the Ebola Virus Disease date = 2019-08-24 pages = extension = .txt mime = text/plain words = 5545 sentences = 245 flesch = 40 summary = Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . Interestingly, evidence collected in animal studies, in the epidemiological analysis of transmission chains, and in the most recent Ebola outbreaks suggests that EBOV may be able to cause primary pulmonary infection. cache = ./cache/cord-003917-bswndfvk.txt txt = ./txt/cord-003917-bswndfvk.txt === reduce.pl bib === id = cord-003772-1345qct4 author = Kummer, Susann title = IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells date = 2019-06-12 pages = extension = .txt mime = text/plain words = 7843 sentences = 417 flesch = 45 summary = title: IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells To determine whether an IAV-induced viral membrane fusion and genome uncoating are required for the observed IFITM3 signal increase upon IAV infection, we performed experiments in the presence of Bafilomycin A1, specifically inhibiting endosomal acidification, or in the presence of Amantadine, specifically blocking the tetrameric M2 channel of IAV, thereby preventing genome uncoating. To determine whether an IAV-induced viral membrane fusion and genome uncoating are required for the observed IFITM3 signal increase upon IAV infection, we performed experiments in the presence of Bafilomycin A1, specifically inhibiting endosomal acidification, or in the presence of Amantadine, specifically blocking the tetrameric M2 channel of IAV, thereby preventing genome uncoating. A strong IFITM3 clustering with a ring-like appearance indicating vesicle coating was observed in both IAV-infected A549 cells ( Figure 5A ) and HSAEpCs at 10 h p.i. cache = ./cache/cord-003772-1345qct4.txt txt = ./txt/cord-003772-1345qct4.txt === reduce.pl bib === id = cord-004022-cr0zskcw author = Lu, Chien-Yi title = The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles date = 2019-10-31 pages = extension = .txt mime = text/plain words = 5532 sentences = 235 flesch = 48 summary = The packaging cells carrying the recombinant plasmid encoding the viral structural proteins are transfected with DNA-launched replicons and then self-replicate viral subgenomes and express all viral proteins, allowing viral assembly and release as SRIPs. Several flavivirus, replicon-based SRIPs, including JEV, dengue virus, West Nile virus, and tick-borne encephalitis virus have been generated and demonstrated as safer vaccine candidates [15] [16] [17] . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) . cache = ./cache/cord-004022-cr0zskcw.txt txt = ./txt/cord-004022-cr0zskcw.txt === reduce.pl bib === id = cord-003861-qeao4ghg author = Aris-Brosou, Stéphane title = Viral Long-Term Evolutionary Strategies Favor Stability over Proliferation date = 2019-07-24 pages = extension = .txt mime = text/plain words = 4513 sentences = 209 flesch = 49 summary = To understand how these two processes affect the long-term evolution of viruses infecting humans, we comprehensively analyzed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus types and which functions show evidence for episodic diversifying selection and correlated evolution. To better understand the role of correlated evolution and positive selection in the evolutionary dynamics of viruses infecting humans, we constructed a nearly exhaustive viral data set spanning all dsDNA, dsRNA, ssRNA, and ssDNA viruses deposited in GenBank (as of August 2017), and conducted an extensive survey of correlated evolution and diversifying selection in these viruses, asking more specifically about the prevalence of these two processes in each viral type, independently or jointly, with the specific hypothesis that the genes affected by both processes encode functions that are most critical to each viral life cycle. cache = ./cache/cord-003861-qeao4ghg.txt txt = ./txt/cord-003861-qeao4ghg.txt === reduce.pl bib === id = cord-003859-k8wfyj9b author = Paweska, Janusz T. title = Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera date = 2019-07-24 pages = extension = .txt mime = text/plain words = 6407 sentences = 308 flesch = 51 summary = title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). The purpose of this study was to evaluate and compare the diagnostic performance of EBOV IgG-indirect ELISAs based on antigens produced by classical virological and recombinant protein expression methods using human serum panels from EBOV non-infected and EBOV infected humans. cache = ./cache/cord-003859-k8wfyj9b.txt txt = ./txt/cord-003859-k8wfyj9b.txt === reduce.pl bib === id = cord-003962-lg6gvgwt author = Zhou, Shaochuan title = Characterizing the PRRSV nsp2 Deubiquitinase Reveals Dispensability of Cis-Activity for Replication and a Link of nsp2 to Inflammation Induction date = 2019-09-26 pages = extension = .txt mime = text/plain words = 10723 sentences = 517 flesch = 56 summary = The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined. Further reverse genetics analyses revealed the following findings: (i) mutations that largely blocked the DUB activity were all lethal to the virus, (ii) a point mutation T88G that selectively blocked the cis-cleavage activity of PLP2 did not affect viral viability in cell culture, and (iii) an E90Q mutation that did not affect either of the PLP2 activities led to rescue of WT-like virus but displayed significantly reduced ability to induce TNF-α production. The results showed that the mutations of the residues D84 and E90 (e.g., D84N, D84R, E90R, E90Q, etc.) did not have much effect on PLP2 DUB activity, as the corresponding mutants could efficiently cleave K63 or K48 polyubiquitin chains into monomers ( Figure 4A , lanes 3, 4, 7, and 8). cache = ./cache/cord-003962-lg6gvgwt.txt txt = ./txt/cord-003962-lg6gvgwt.txt === reduce.pl bib === 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 pages = extension = .txt mime = text/plain words = 8868 sentences = 441 flesch = 52 summary = Antigen-specific IgG responses induced by immunization with the vaccine candidates were analyzed by enzyme-linked immunosorbent assay (ELISA) using purified soluble recombinant NiV glycoprotein G expressed in mammalian HEK293 cells. IFNAR−/− mice on a C57BL/6 background (MHC I = H2-Db/H2-Kb (H2-b) and MHC II = H2-IAb) were immunized twice with the MVA-NiVsG candidate vaccine via the intraperitoneal (i.p.) route, and splenocytes were prepared 8 days after the final inoculation, CD4 and CD8 T cells were purified and restimulated with overlapping 15mer peptides corresponding to the NiV-G protein. IFNAR−/− mice on a C57BL/6 background (MHC I = H2-Db/H2-Kb (H2-b) and MHC II = H2-IAb) were immunized twice with the MVA-NiVsG candidate vaccine via the intraperitoneal (i.p.) route, and splenocytes were prepared 8 days after the final inoculation, CD4 and CD8 T cells were purified and restimulated with overlapping 15mer peptides corresponding to the NiV-G protein. cache = ./cache/cord-004334-y1fcw1dj.txt txt = ./txt/cord-004334-y1fcw1dj.txt === reduce.pl bib === === reduce.pl bib === id = cord-004507-ezuyjcxs author = Tomazatos, Alexandru title = Letea Virus: Comparative Genomics and Phylogenetic Analysis of a Novel Reassortant Orbivirus Discovered in Grass Snakes (Natrix natrix) date = 2020-02-21 pages = extension = .txt mime = text/plain words = 6326 sentences = 348 flesch = 49 summary = The study provided complete genome sequences for nine Letea virus strains and new information about orbivirus diversity, host range, ecology and evolution. The phylogenetic clustering of Orbivirus members results in clades indicating their putative or potential arthropod vectors: Culicoidesor sand fly-borne (C/SBOV), mosquito-borne (MBOV) and tick-borne orbiviruses (TBOV) [9] . Evolutionary relationship of LEAV with representative members of the Orbivirus genus were analyzed by inferring phylogenetic trees with amino acid and nucleotide ORF sequences of conserved genes encoding the polymerase (VP1), the subcore shell protein T2 (VP2/VP3) and the major core surface protein T13 (VP7) [5, 6] . Inclusion and demarcation of species within the Orbivirus genus considers several criteria, such as sequence identity of segments encoding the polymerase (VP1) and major subcore shell protein T2, gene reassortment between close strains, high levels of serological cross-reactivity against conserved antigens like the T13 protein, conservation of UTR terminal nucleotides, range of hosts and vectors or the clinical signs associated with orbivirus infection [1] . cache = ./cache/cord-004507-ezuyjcxs.txt txt = ./txt/cord-004507-ezuyjcxs.txt === reduce.pl bib === id = cord-004509-jkzqmkz6 author = Thirion, Laurence title = Lyophilized Matrix Containing Ready-to-Use Primers and Probe Solution for Standardization of Real-Time PCR and RT-qPCR Diagnostics in Virology date = 2020-01-30 pages = extension = .txt mime = text/plain words = 4393 sentences = 194 flesch = 47 summary = In conclusion, Lyoph-P&P holds several advantages over extemporaneously preparer liquid formulation that merit to be considered when a novel real-time molecular assay is implemented in a laboratory in charge of routine diagnostic activity. Selected assays target two emerging viruses that are listed on the blueprint of the WHO as to be considered for preparedness and response actions [5] : chikungunya virus (CHIKV), a single-stranded positive-sense RNA alphavirus, and Rift Valley fever phlebovirus (RVFV), a tri-segmented, single-stranded negative-sense RNA phlebovirus. Detection of CHIKV RNA using Lyoph-P&P provides results in clinical samples that are at least equal and often better than those obtained with the extemporaneously prepared liquid formulation used as reference. Indeed, at laboratory level, it is likely that one or two different formats (number of tests per vial) will be either prepared or ordered; as a consequence, the time during which rehydrated material can be stored without affecting the expected performances of the assay is a key factor. cache = ./cache/cord-004509-jkzqmkz6.txt txt = ./txt/cord-004509-jkzqmkz6.txt === reduce.pl bib === id = cord-004508-ok3px98z author = Armando, Federico title = Oxidative Stress in Canine Histiocytic Sarcoma Cells Induced by an Infection with Canine Distemper Virus Led to a Dysregulation of HIF-1α Downstream Pathway Resulting in a Reduced Expression of VEGF-B In Vitro date = 2020-02-11 pages = extension = .txt mime = text/plain words = 8265 sentences = 382 flesch = 38 summary = Based on these findings, the aim of the present study was to investigate the impact of a persistent CDV-infection on oxidative stress mediated changes in the expression of hypoxia-inducible factor (HIF)-1α and its angiogenic downstream pathway in DH82 cells in vitro. In summary, these results suggest a reduced activation of the HIF-1α angiogenic downstream pathway in DH82Ond pi cells in vitro, most likely due to an excessive, unusually localized, and non-functional expression of HIF-1α triggered by a CDV-induced increased oxidative stress. In a hypothesis-driven approach, an online available microarray data set of quadruplicates of non-infected DH82 and DH82Ond pi cells (ArrayExpress; http://www.ebi.ac.uk/arrayexpress; accession number E-MTAB-3942 [11, 44] ) was investigated for differentially expressed genes related to ROS production and scavenging, ER-stress and HIF-1α pathway, with a special focus on the angiogenic downstream targets of the latter. cache = ./cache/cord-004508-ok3px98z.txt txt = ./txt/cord-004508-ok3px98z.txt === reduce.pl bib === id = cord-011435-x73foqu7 author = Glanz, Anna title = High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication date = 2020-04-14 pages = extension = .txt mime = text/plain words = 8401 sentences = 469 flesch = 39 summary = title: High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication Previously, we uncovered a function for nontranscriptional IRF3 (nt-IRF3), RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA), which triggers apoptotic killing of virus-infected cells. In contrast to the transcriptional pathway, nt-Irf3 in virus-infected cells functions as a chaperone protein by translocating the pro-apoptotic protein BCL2-associated X (BAX) to the mitochondria, thereby causing apoptotic cell death, which we named RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA) ( Figure 1A ) [7] [8] [9] [10] [11] [12] [13] . We validated these results by immunoblot analyses, which demonstrate that doxorubicin treatment inhibited the expression of VSV-G protein, a viral envelope glycoprotein as well as the virus-encoded GFP ( Figure 3B ). We validated these results by immunoblot analyses, which demonstrate that doxorubicin treatment inhibited the expression of VSV-G protein, a viral envelope glycoprotein as well as the virus-encoded GFP ( Figure 3B ). cache = ./cache/cord-011435-x73foqu7.txt txt = ./txt/cord-011435-x73foqu7.txt === reduce.pl bib === id = cord-004337-jtaz1gdp author = Wu, Fangfang title = A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses date = 2020-01-03 pages = extension = .txt mime = text/plain words = 5721 sentences = 283 flesch = 53 summary = title: A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses Here, we report that production of SUDV VLPs has been accomplished in insect cells by the co-infection with recombinant baculoviruses rBV-GP-GP and rBV-VP40-VP40, and evaluate the ability of SUDV-VLPs to induce SUDV-specific humoral and cellular immune responses in vaccinated mice. To detect a SUDV-VLP-induced humoral immune response in vaccinated BALB/c mice, indirect ELISA and virus neutralization assay were performed to evaluate the production of SUDV GP-specific antibodies and neutralizing antibodies. Analysis of SUDV-VLP-induced specific IgG antibody response by indirect ELISA at two weeks after every immunization of vaccinated mice (C). Moreover, our study revealed that the B cells of mice of the group vaccinated with SUDV VLPs mixed with an ISA 201 adjuvant were activated at one week after the primary immunization (Figure 7 ). cache = ./cache/cord-004337-jtaz1gdp.txt txt = ./txt/cord-004337-jtaz1gdp.txt === 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 === id = cord-009399-6zpkpdzu author = Sun, Fang title = Topology, Antiviral Functional Residues and Mechanism of IFITM1 date = 2020-03-08 pages = extension = .txt mime = text/plain words = 5697 sentences = 354 flesch = 57 summary = Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Some studies suggest that IFITM proteins may suppress the entry of viruses by inhibiting the hemifusion of viral membrane and host cell membranes [15] or restricting the formation of fusion pores following virus-endosome hemifusion [16] . Alanine scanning and site-directed mutations found that KRRK basic residues were key for the restriction of IFITM proteins on ZIKV and DENV. Significantly, we found that IFITM1 can restrict the release of ZIKV from endosome to cytosol to prevent the entry of viral particles into host cells, which was associated with its inhibition on organelles acidification. cache = ./cache/cord-009399-6zpkpdzu.txt txt = ./txt/cord-009399-6zpkpdzu.txt === reduce.pl bib === id = cord-013174-whg64w0w author = Bhatta, Tarka Raj title = Infection Dynamics of Swine Influenza Virus in a Danish Pig Herd Reveals Recurrent Infections with Different Variants of the H1N2 Swine Influenza A Virus Subtype date = 2020-09-10 pages = extension = .txt mime = text/plain words = 8213 sentences = 427 flesch = 59 summary = In addition, next generation sequencing (NGS) was used to identify and characterize the complete genome of swIAV circulating in the herd, and to examine the antigenic variability in the antigenic sites of the virus hemagglutinin (HA) and neuraminidase (NA) proteins. In pigs, circulation of IAV, so-called swine influenza A virus (swIAV), is currently mainly limited to three different subtypes including H1N1, H1N2 and H3N2 [5] [6] [7] . In the phylogenetic analysis, the HA sequences of pig ID 250, obtained at weeks 4 and 8 were located in the same cluster and were~0.5% (9/1701) divergent at the nucleotide level and < 1% (5/566) divergent at the amino acid level. Comparison of amino acid sequences of neuraminidase (NA) antigenic sites of pig ID 380 sampled at week 5 and week 22 from the pig herd. cache = ./cache/cord-013174-whg64w0w.txt txt = ./txt/cord-013174-whg64w0w.txt === reduce.pl bib === id = cord-011635-vosu7y6j author = Norlander, Allison E. title = Innate Type 2 Responses to Respiratory Syncytial Virus Infection date = 2020-05-08 pages = extension = .txt mime = text/plain words = 8260 sentences = 458 flesch = 46 summary = This review summarizes the contribution of a newly described cell type, group 2 innate lymphoid cells (ILC2), and epithelial-derived alarmin proteins that activate ILC2, including IL-33, IL-25, thymic stromal lymphopoietin (TSLP), and high mobility group box 1 (HMGB1). Furthermore, the epithelial-derived cytokines interleukin-33 (IL-33), interleukin-25 (IL-25), and thymic stromal lymphopoietin (TSLP), as well as the innate immune cell-derived cytokine high mobility group box 1 (HMGB1), activate and induce ILC2 function, thereby promoting the progression of type 2-mediated pulmonary diseases ( Figure 1 ) [59] [60] [61] [62] [63] [64] . These alarmin proteins released from RSV-infected epithelial cells can activate group 2 innate lymphoid cells (ILC2) to produce the type 2 cytokines IL-5 and IL-13. These alarmin proteins released from RSV-infected epithelial cells can activate group 2 innate lymphoid cells (ILC2) to produce the type 2 cytokines IL-5 and IL-13. Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection cache = ./cache/cord-011635-vosu7y6j.txt txt = ./txt/cord-011635-vosu7y6j.txt === reduce.pl bib === id = cord-011438-imbpgsub author = Zhang, Yun title = Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection date = 2020-03-29 pages = extension = .txt mime = text/plain words = 9294 sentences = 567 flesch = 41 summary = Upon IAV infection, host innate immune system is triggered and activated to restrict virus replication and clear pathogens. 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. Host innate immunity, including phagocytic cells, interferons (IFNs), proinflammatory cytokines, etc., applies multiple mechanisms in defending IAV infection [105] . Influenza A virus nucleoprotein induces apoptosis in human airway epithelial cells: Implications of a novel interaction between nucleoprotein and host protein Clusterin Antiviral response elicited against avian influenza virus infection following activation of toll-like receptor (TLR)7 signaling pathway is attributable to interleukin (IL)-1β production The human interferon-induced MxA protein inhibits early stages of influenza A virus infection by retaining the incoming viral genome in the cytoplasm Cell death regulation during influenza A virus infection by matrix (M1) protein: A model of viral control over the cellular survival pathway cache = ./cache/cord-011438-imbpgsub.txt txt = ./txt/cord-011438-imbpgsub.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-004018-33zi29bg author = Coombs, Kevin M. title = Aptamer Profiling of A549 Cells Infected with Low-Pathogenicity and High-Pathogenicity Influenza Viruses date = 2019-11-05 pages = extension = .txt mime = text/plain words = 5373 sentences = 252 flesch = 43 summary = We used a newly-developed aptamer-based multiplexed technique (SOMAscan(®)) to examine >1300 human lung cell proteins affected by the different IAV strains, and identified more than 500 significantly dysregulated cellular proteins. The PR8 strain induced a general activation, primarily by upregulating many immune molecules, the seasonal RV733 and pdm09 strains had minimal effect upon assayed molecules, and the avian strains induced significant downregulation, primarily in antimicrobial response, cardiovascular and post-translational modification systems. We found that the culture-adapted PR8 strain had an overall activation of immune molecules, the mild seasonal and pdm09 human strains had little effect upon the molecules targeted by the SOMA panel, and the avian H5N1 and H7N9 strains, that are much more pathogenic in humans, had the most dramatic proteomic responses, these upregulating a few tested molecules, but inhibiting many more key cellular processes. Quantitative proteomic analyses of influenza virus-infected cultured human lung cells Quantitative analysis of cellular proteome alterations in human influenza A virus-infected mammalian cell lines cache = ./cache/cord-004018-33zi29bg.txt txt = ./txt/cord-004018-33zi29bg.txt === reduce.pl bib === 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 pages = extension = .txt mime = text/plain words = 15685 sentences = 761 flesch = 38 summary = 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. The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ). The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ). cache = ./cache/cord-012418-6ralcn8p.txt txt = ./txt/cord-012418-6ralcn8p.txt === reduce.pl bib === id = cord-013177-whd0znan author = Han, Zhenzhi title = The Husavirus Posa-Like Viruses in China, and a New Group of Picornavirales date = 2020-09-07 pages = extension = .txt mime = text/plain words = 5049 sentences = 265 flesch = 44 summary = Novel posa-like viral genomes were first identified in swine fecal samples using metagenomics and were designated as unclassified viruses in the order Picornavirales. These posa-like viruses have undergone a complex evolutionary process, and have a wide geographic distribution, complex host spectrum, deep phylogenetic divergence, and diverse genomic organizations. Novel posa-like virus genomes were first identified in swine fecal samples using metagenomics and were assigned as unclassified viruses to the order Picornavirales [12] . Further reports of novel posaviruses with low amino acid sequence identity revealed novel genomic organization features and phylogenetic characteristics of posa-like viruses [15, 16] . Due to the low genomic sequence similarity between the husavirus and unclassified posa-like viruses in Picornavirales, it was difficult to perform a phylogenetic analysis at the full-length genome level. Posa-like viruses identified in previous reports and in the present study formed a single group and clustered with the genomes of family Marnaviridae (Figure 4) . cache = ./cache/cord-013177-whd0znan.txt txt = ./txt/cord-013177-whd0znan.txt === reduce.pl bib === id = cord-012420-llh22iq2 author = Stott, Robert J. title = Distinct Molecular Mechanisms of Host Immune Response Modulation by Arenavirus NP and Z Proteins date = 2020-07-21 pages = extension = .txt mime = text/plain words = 12015 sentences = 579 flesch = 41 summary = Interestingly, non-pathogenic OW Mopeia virus (MOPV), a close genetic relative to LASV, induces a strong initial IFN and cytokine response in infected moDCs and macrophages leading to a sustained T cell activation and immune response [67, 68] . Similar to NP, interaction of arenavirus Z proteins with RIG-I prevents further binding to MAVS and therefore inhibits the production of IFN-β and reduces antiviral host immune responses. Although the inhibition of RIG-I signalling by highly pathogenic arenaviruses in vitro suggests that there should be limited IFN1 response, it is notable that in vivo infection with some of these viruses (LCMV, JUNV) induces high levels of IFN1, ISGs and cytokines suggesting that this strategy is not completely effective or is widely varied in cell type and differs from host to host [134, 135, 186] . cache = ./cache/cord-012420-llh22iq2.txt txt = ./txt/cord-012420-llh22iq2.txt === reduce.pl bib === id = cord-252142-aqwlcs9g author = Uematsu, Jun title = Legume Lectins Inhibit Human Parainfluenza Virus Type 2 Infection by Interfering with the Entr date = 2012-06-29 pages = extension = .txt mime = text/plain words = 3037 sentences = 167 flesch = 55 summary = Three lectins with different sugar binding specificities were investigated for anti-viral activity against human parainfluenza virus type 2 (hPIV-2). The lectins, concanavalin A (Con A), lens culinaris agglutinin (LCA) and peanut agglutinin (PNA), inhibited cell fusion and hemadsorption induced by hPIV-2. Using a recombinant green fluorescence protein-expressing hPIV-2, without matrix protein (rghPIV-2ΔM), it was found that virus entry into the cells was not completely prevented. The inhibitory effect of lectins on hPIV-2 entry into the cells and replication in the cells was analyzed using a recombinant green fluorescence protein-expressing hPIV-2 without matrix (M) protein (rghPIV-2ΔM) [9] . RNA was prepared from the lectin-treated infected cells at four days post infection, and virus-synthesized RNA was analyzed using hPIV-2 specific primers by polymerase chain reaction (PCR). These results indicated that the lectins bound to the cell surface receptors, and largely prevented the binding of hPIV-2 to the cells non-specifically. cache = ./cache/cord-252142-aqwlcs9g.txt txt = ./txt/cord-252142-aqwlcs9g.txt === reduce.pl bib === id = cord-254181-nquozaxt author = Sieg, Michael title = A New Genotype of Feline Morbillivirus Infects Primary Cells of the Lung, Kidney, Brain and Peripheral Blood date = 2019-02-09 pages = extension = .txt mime = text/plain words = 8567 sentences = 434 flesch = 50 summary = To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. To elucidate the target tissues of FeMV-GT2 we established protocols for the isolation of primary feline cells from various organs of cats (see section 2.2.) Experimental in vitro infection was performed using the LLC-MK2-adapted FeMV-GT2-Gordon strain. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. cache = ./cache/cord-254181-nquozaxt.txt txt = ./txt/cord-254181-nquozaxt.txt === reduce.pl bib === id = cord-255683-2eq24jth author = Chen, Weizao title = Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins date = 2010-02-04 pages = extension = .txt mime = text/plain words = 5927 sentences = 290 flesch = 47 summary = Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. To find whether the activity of the antibodies is related to antibody size and how the viral infection could be affected by cross-linking of HIV-1 Envs, we generated a single-chain Fv fragment (scFv) (scFv m19) of m19 and a human IgG1 Fc-fusion protein (m19Fc) of scFv m19; m19 was selected for further characterization because its light chain was relatively less divergent from the germline ( Figure 1b) and was the only one which did not contain any somatic mutations in the CDR3 of the light chain. cache = ./cache/cord-255683-2eq24jth.txt txt = ./txt/cord-255683-2eq24jth.txt === reduce.pl bib === id = cord-257665-12gyrmh2 author = Liu, Shan-Lu title = Emerging Viruses without Borders: The Wuhan Coronavirus date = 2020-01-22 pages = extension = .txt mime = text/plain words = 790 sentences = 48 flesch = 56 summary = We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists, but we also believe that increased transparency on disease reporting and data sharing with international colleagues are crucial for curbing the spread of this newly emerging virus to other parts of the world. We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists, but we also believe that increased transparency on disease reporting and data sharing with international colleagues are crucial for curbing the spread of this newly emerging virus to other parts of the world. We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists [3] , as this represents an important first step in curbing the spread of the new virus to other parts of the world. cache = ./cache/cord-257665-12gyrmh2.txt txt = ./txt/cord-257665-12gyrmh2.txt === reduce.pl bib === id = cord-254250-l0v602x9 author = Hooper, Chantelle title = A Novel RNA Virus, Macrobrachium rosenbergii Golda Virus (MrGV), Linked to Mass Mortalities of the Larval Giant Freshwater Prawn in Bangladesh date = 2020-10-02 pages = extension = .txt mime = text/plain words = 6440 sentences = 309 flesch = 48 summary = title: A Novel RNA Virus, Macrobrachium rosenbergii Golda Virus (MrGV), Linked to Mass Mortalities of the Larval Giant Freshwater Prawn in Bangladesh De novo virus assembly revealed a 29 kb single-stranded positive-sense RNA virus with similarities in key protein motif sequences to yellow head virus (YHV), an RNA virus that causes mass mortalities in marine shrimp aquaculture, and other viruses in the Nidovirales order. rnaSPAdes assembly of combined libraries produced 38,826 contigs; 23 contigs, of average length 4560 bp, had similarity in protein sequence to YHV or gill-associated virus (GAV), but when the trimmed reads were aligned against the YHV genome (accession number GCA_003972805.1), no alignment was seen. rosenbergii were negative: MrNV and XSV, the causative agents of white tail disease [9, 10] ; MrTV, a virus associated with mass larval mortalities in China [15] , Spiroplasma eriocheiris [8] , and WSSV-shown to be able to infect M. cache = ./cache/cord-254250-l0v602x9.txt txt = ./txt/cord-254250-l0v602x9.txt === reduce.pl bib === === reduce.pl bib === id = cord-257913-uf9sx5qi author = Dijkman, Ronald title = Seroconversion to HCoV-NL63 in Rhesus Macaques date = 2009-10-30 pages = extension = .txt mime = text/plain words = 2794 sentences = 155 flesch = 57 summary = Alternatively, one can establish whether rhesus macaques that are in close contact to humans have experienced a natural HCoV-NL63 infection by investigating the NL63-directed antibody titers in time. In the current study we use the kinetics of the antibody response to HCoV-NL63 to determine whether rhesus macaques encounter natural infections with HCoV-NL63, or related coronaviruses. The first indication of infections with HCoV-NL63-like viruses in rhesus macaques was found when we tested 32 serum samples of 32 monkeys (Table 1 and Figure 1 ). Longitudinal serum samples were available of three rhesus macaques with the highest antibody levels to HCoV-NL63 (numbers 5, 10 and 17). A well-designed follow up through the years with serum and respiratory samples collected on a regular basis would be sufficient to unravel the potential of the human respiratory viruses to infect rhesus macaques. We show here that there are clear signs that Rhesus macaques acquire natural infections with HCoV-NL63, or a serologically very closely related coronavirus. cache = ./cache/cord-257913-uf9sx5qi.txt txt = ./txt/cord-257913-uf9sx5qi.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-258323-vdeffy4l author = Jiang, Yuting title = Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV date = 2019-01-09 pages = extension = .txt mime = text/plain words = 4770 sentences = 253 flesch = 48 summary = To detect expression of inflammasomes and complement components in MERS-CoV-infected THP-1 differentiated macrophages and hDPP4-Tg mice, 2 µg of total RNA from cells or the lung of mice we used as template for first-strand cDNA synthesis. IHC examination of CD68 and IFN-γ receptor expression also suggested greater macrophage infiltration and activation in the lung and spleen of mice at 7 days post-MERS-CoV infection ( Figure 3D ). IHC examination of CD68 and IFN-γ receptor expression also suggested greater macrophage infiltration and activation in the lung and spleen of mice at 7 days post-MERS-CoV infection ( Figure 3D ). These results suggest that complement inhibition decreased the expression of pyroptosis indicators, IL-1β and caspase-1, in mice infected with MERS-CoV. Here, our results showed that MERS-CoV infection induces pro-IL-1β transcription, and complement activation, which leads to pyroptosis in macrophages. Here, our results showed that MERS-CoV infection induces pro-IL-1β transcription, and complement activation, which leads to pyroptosis in macrophages. cache = ./cache/cord-258323-vdeffy4l.txt txt = ./txt/cord-258323-vdeffy4l.txt === reduce.pl bib === id = cord-259237-aty0vrat author = Frabutt, Dylan A. title = Arms Race between Enveloped Viruses and the Host ERAD Machinery date = 2016-09-19 pages = extension = .txt mime = text/plain words = 9770 sentences = 508 flesch = 42 summary = One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. The remaining Man residues are cleaved by the Golgi mannosidases, and the glycan remolding process is continued through the remainder of the N-glycosylation pathway, which generates functional glycoproteins that are delivered to the cell surface ( Figure 1B ). As introduced earlier, the UPR utilizes three different mechanisms to alleviate ER stress: reducing global protein translation, increasing the ER folding capacity, and enhancing ERAD by activating the PERK, ATF6, or IRE1-XBP1 pathways, respectively. ERManI also targets the terminally misfolded human alpha1-antitrypsin variant null (Hong Kong) (NHK) for degradation via ERAD, but neither its catalytic activity nor its catalytic domain is required for this degradation, suggesting that different mechanisms are involved in HIV-1 Env and NHK degradation [152] . The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway cache = ./cache/cord-259237-aty0vrat.txt txt = ./txt/cord-259237-aty0vrat.txt === reduce.pl bib === id = cord-256924-c7ftvgio author = Mackay, Ian M. title = Co-circulation of Four Human Coronaviruses (HCoVs) in Queensland Children with Acute Respiratory Tract Illnesses in 2004 date = 2012-04-23 pages = extension = .txt mime = text/plain words = 4409 sentences = 236 flesch = 49 summary = Positive specimens were used to develop novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. Severity scores were similar to those from a random selection of young children who were positive for respiratory syncytial virus at a different time but from the same specimen population. Recently three new HCoVs, all detected in patients with ARIs were described; the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, HCoV-NL63 in 2004 and HCoV-HKU1 in 2005 [16] [17] [18] . Our retrospective study also observed that clinical features and the average severity scores from patients with HCoV were very close to those from a similarly aged set of children who were positive for HRSV. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method Frequent detection of human coronaviruses in clinical specimens from patients with respiratory tract infection by use of a novel real-time reverse-transcription polymerase chain reaction cache = ./cache/cord-256924-c7ftvgio.txt txt = ./txt/cord-256924-c7ftvgio.txt === reduce.pl bib === === reduce.pl bib === id = cord-258536-qnn9hp8e author = Cong, Yingying title = The Interaction between Nidovirales and Autophagy Components date = 2017-07-11 pages = extension = .txt mime = text/plain words = 6566 sentences = 358 flesch = 44 summary = The nsp proteins interfere with the host defenses but also induce the formation of double-membrane vesicles (DMVs) and convoluted membranes, on which they collectively form the replication-transcription complexes (RTCs) [19, 20] (Figure 2 , steps 2, 3, and 4). These complexes mediate the synthesis of the genomic RNA and a nested set of subgenomic RNAs that directs the translation of the structural proteins (the nucleocapsid N protein, the membrane M protein, the envelope E protein and the spike S protein) and some accessory proteins, like the hemagglutinin esterase in the case of Severe Acute Respiratory Syndrome (SARS)-CoV or Mouse Hepatitis Virus (MHV) [21] [22] [23] (Figure 2 , steps 5 and 6). Infected cells displayed the presence of a higher number of autophagosome-like double-membrane vesicles, an accumulation of green fluorescent protein (GFP)-LC3-positive puncta and higher levels of lipidated LC3, indicating an induction of autophagy [57] . cache = ./cache/cord-258536-qnn9hp8e.txt txt = ./txt/cord-258536-qnn9hp8e.txt === reduce.pl bib === id = cord-259273-bh5csogu author = Fathima, Sumana title = Use of an Innovative Web-Based Laboratory Surveillance Platform to Analyze Mixed Infections Between Human Metapneumovirus (hMPV) and Other Respiratory Viruses Circulating in Alberta (AB), Canada (2009–2012) date = 2012-11-05 pages = extension = .txt mime = text/plain words = 3239 sentences = 150 flesch = 46 summary = mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. A cost effective approach was adopted in June 2009, to only test specimens negative for both influenza A and B by either singleplex or multiplex real time PCR assays using the Respiratory Virus Panel (RVP) classic assay, a multiplexed assay which detects multiple respiratory viral pathogens including FLUA, FLUB, PIV, ERV, ADV, 4 types of CRV, RSV, and hMPV [15] . In this study we used DIAL to select specimen-based data and investigated the proportions of mono vs mixed infections for hMPV as compared to ADV, CRV, ERV, PIV and RSV for a period of three years, 1 July 2009 to 30 June 2012. cache = ./cache/cord-259273-bh5csogu.txt txt = ./txt/cord-259273-bh5csogu.txt === reduce.pl bib === id = cord-262434-q4tk96tq author = Baker, Kate S. title = Poxviruses in Bats … so What? date = 2014-04-03 pages = extension = .txt mime = text/plain words = 3331 sentences = 175 flesch = 42 summary = Finally, we speculate on the possible consequences and potential research avenues opened following this marrying of a pathogen of great historical and contemporary importance with an ancient host that has an apparently peculiar relationship with viruses; a fascinating and likely fruitful meeting whose study will be facilitated by recent technological advances and a heightened interest in bat virology. Similarly, testing the in vitro host range of isolated viruses such as Eptesipox virus would help inform whether human and further animal cell lines are permissive for infection (i.e., that they contain the necessary host factors to support infection and do not contain antiviral components that restrict infection). Further field (in situ), in vitro and in silico studies could elucidate the possible coevolution, cross species infections and mechanisms of host range restriction of bat poxviruses, the implications of which are relevant for bat ecologists, virologists and emerging infectious disease specialists (including those with a specific interest in bats) alike. cache = ./cache/cord-262434-q4tk96tq.txt txt = ./txt/cord-262434-q4tk96tq.txt === reduce.pl bib === id = cord-257539-01s21vh0 author = Delvecchio, Rodrigo title = Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models date = 2016-11-29 pages = extension = .txt mime = text/plain words = 5669 sentences = 290 flesch = 52 summary = Immunofluorescence staining corroborated these results ( Figure 1B ) and additionally, chloroquine decreased the production of infectious ( Figure 1C ) and total ( Figure 1D ) virus particles, including defective viral particles, by ZIKV-infected cells. Incubation of Vero cells with chloroquine at 0 h postinfection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ). To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. Incubation of Vero cells with chloroquine at 0 h post-infection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ). cache = ./cache/cord-257539-01s21vh0.txt txt = ./txt/cord-257539-01s21vh0.txt === reduce.pl bib === === reduce.pl bib === id = cord-261417-4pf5nsw2 author = Harwig, Alex title = The Battle of RNA Synthesis: Virus versus Host date = 2017-10-21 pages = extension = .txt mime = text/plain words = 7864 sentences = 443 flesch = 53 summary = Why the virus prefers to use these snRNAs as targets has yet to be experimentally established, but it has been proposed that the selective de-capping of U1 and U2 RNAs in combination with the binding of the viral NS1 protein to U6 snRNA may serve to inhibit host pre-mRNA splicing [66] . The folding of the TAR hairpin is key to the regulation of HIV-1 transcription [94] as it is used as a scaffold to recruit essential transcription factors, including the 86-101 amino acid (aa) viral trans-activator protein (Tat) [83] ( Figure 3C ). Interestingly, the human T-lymphotropic virus type 1 transcriptional activator Tax also utilizes P-TEFb for viral transcription and displaces P-TEFb from 7SK snRNP through binding CycT1 [101, 102] , suggesting that P-TEFb liberation from 7SK snRNP could be a common theme developed by different viruses to support their replication in host cells. cache = ./cache/cord-261417-4pf5nsw2.txt txt = ./txt/cord-261417-4pf5nsw2.txt === reduce.pl bib === id = cord-265679-7gzont7l author = Guo, Nan title = Caerin1.1 Suppresses the Growth of Porcine Epidemic Diarrhea Virus In Vitro via Direct Binding to the Virus date = 2018-09-18 pages = extension = .txt mime = text/plain words = 5241 sentences = 270 flesch = 52 summary = In this study, the antiviral activity of a cationic amphibian antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV) was evaluated by an in vitro system using Vero cells. Vero cells cultured in 24-well plates were washed with PBS for 3 times and inoculated respectively with single medium, or single PEDV, or PEDV pre-incubated with different concentrations of Caerin1.1. PEDV suspensions containing different concentrations of Caerin1.1 were pre-incubated for 1 h at 37 • C, and were serially diluted before they were inoculated on the 80% confluent Vero cell monolayers grown in the 96-well plates, followed by washing 3 times with PBS. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1. cache = ./cache/cord-265679-7gzont7l.txt txt = ./txt/cord-265679-7gzont7l.txt === reduce.pl bib === id = cord-260705-huyyw5z6 author = Moshe, Adi title = Virus-Induced Aggregates in Infected Cells date = 2012-10-17 pages = extension = .txt mime = text/plain words = 5063 sentences = 265 flesch = 39 summary = During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intraand intercellular transportation. In plant cells, both RNA and DNA viruses are associated with large inclusions detected in the cytoplasm and nucleus, however, their role in virus propagation or oppositely in virus restraint is less investigated than in infected mammalian cells. In general, mammalian and plant viruses make use of aggregates as scaffolds for anchoring the replication complex, increasing the local concentration of viral and host components required for replication and assembly, and shielding the process of replication from host defense. cache = ./cache/cord-260705-huyyw5z6.txt txt = ./txt/cord-260705-huyyw5z6.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-263315-g7os15m1 author = Martins-da-Silva, Andrea title = Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response date = 2018-01-18 pages = extension = .txt mime = text/plain words = 6975 sentences = 460 flesch = 48 summary = title: Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response The two most abundant secreted peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an interferon-inducible protein that mediates antiviral activity, and forskolin-binding protein (FKBP), a member of the immunophilin family, which mediates the effect of immunosuppressive drugs. In human and mouse plasmacytoid dendritic cells (pDCs), which are professional interferon-producing cells specialized in recognizing viral RNA and DNA through the endosomal Toll-like receptors (TLRs) TLR7 and TLR9, respectively, PLSCR1 was described as a TLR9-binding protein that plays a significant role in type-1 interferon responses in pDCs by regulating TLR9 expression and trafficking [57] . Binding of FKBP51 to TRAF proteins facilitates the type-I interferon response induced by dsRNA transfection or Newcastle disease virus (NDV) infection in murine fibroblasts. Binding of FKBP51 to TRAF proteins facilitates the type-I interferon response induced by dsRNA transfection or Newcastle disease virus (NDV) infection in murine fibroblasts. cache = ./cache/cord-263315-g7os15m1.txt txt = ./txt/cord-263315-g7os15m1.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-267709-i2loz1xb author = Li, Tongya title = Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200 date = 2019-05-09 pages = extension = .txt mime = text/plain words = 6910 sentences = 387 flesch = 51 summary = title: Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200 Finally, the antiviral effects of IFITM1 on cell proliferation and HBV replication were found to be partially restored when HBc was co-transfected with BAF200. Finally, our data demonstrates that the antiviral effects of IFITM1 on cellular proliferation and HBV replication are partially restored when HBc is co-expressed with BAF200 in HBV-infected cells. First, BAF200C was co-transfected with either empty vectors or HBc into 293T cells, then the whole cell lysate was immunoprecipitated by an anti-Flag antibody and then subjected to western blot by anti-HA antibodies to detect the interacting proteins. (d) HepG2 cells were co-transfected with the pGC-FU-Flag-BAF200 and pCMV-HA vectors or pCMV-HA-HBc, and co-IP assays were carried out with anti-HA antibody or IgG. We co-transfected HBc and BAF200 into HepG2 cells, treated the cells with 500 U/mL IFNα, and detected the expression of IFITM1 by western blot (Figure 2d ). cache = ./cache/cord-267709-i2loz1xb.txt txt = ./txt/cord-267709-i2loz1xb.txt === reduce.pl bib === id = cord-267012-45tre8rn author = Premanand, Balraj title = Baculovirus Surface Display of Immunogenic Proteins for Vaccine Development date = 2018-05-31 pages = extension = .txt mime = text/plain words = 11102 sentences = 530 flesch = 34 summary = While recombinant baculoviral vector expressing both VSV-G and influenza HA was shown to evoke both humoral and cellular immune responses and provided effective protection against lethal virus challenge in mouse and chicken hosts [26] , the high cytotoxicity of VSV-G protein [98] and its immediate inactivation by serum complement systems impedes the use of the element in a vaccine delivery vehicle [99] . The vaccine showed successful HA expression on its envelope, and mice vaccination studies showed that both the live and adjuvanted with inactive form of recombinant baculovirus induced HA-specific antibody responses and offered complete protection against lethal viral infection [101] . Moreover, recombinant baculovirus with CMV-polyhedrin dual promoter for expressing chimeric HA of H9N2 was shown to efficiently express HA in both mammalian and insect cells, induce strong immune response, and provide 100% protection against lethal H9N2 viral challenge in mice, unlike other vaccine candidates observed [34] . cache = ./cache/cord-267012-45tre8rn.txt txt = ./txt/cord-267012-45tre8rn.txt === reduce.pl bib === id = cord-263142-o8qbqxhx author = Cavalcante, Liliane T. F. title = Clinical and Molecular Features of Feline Foamy Virus and Feline Leukemia Virus Co-Infection in Naturally-Infected Cats date = 2018-12-11 pages = extension = .txt mime = text/plain words = 9123 sentences = 432 flesch = 52 summary = We examined blood and buccal swab specimens of domestic cats in Brazil for detection and quantification of each feline virus to evaluate their potential association with disease and transmissibility in animals with single or multiple retroviral infections. Buccal swab gDNA from 33 nested PCR-negative animals identified seven qPCR positive cats with a median pVL of −0.7 log10 copies/cell (201,363 copies/10 6 cells). Analysis of cats classified as potentially transmissible and non-transmissible found no statistical difference between FFV pVLs. Of 27 FeLV-positive cats diagnosed by serological and/or molecular assays, 26 with available PBMC gDNA were FeLV qPCR-positive with a median pVL of 2.11 log10 copies/cell (1.29 × 10 8 copies/10 6 cells) ( Figure 1B) . Testing of 35 buccal swab gDNA samples identified four qPCR-positive cats with a median FeLV pVL of −0.55 log10 copies/cell (2.91 × 10 5 copies/10 6 cells). cache = ./cache/cord-263142-o8qbqxhx.txt txt = ./txt/cord-263142-o8qbqxhx.txt === reduce.pl bib === id = cord-253282-zwl0safn author = Plant, Ewan P. title = Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production date = 2013-01-18 pages = extension = .txt mime = text/plain words = 5007 sentences = 266 flesch = 55 summary = In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. Here, analyses using synonymous protein coding mutations demonstrate that the region of the genome that harbors the frameshift signal affects the regulation of genomic and subgenomic RNA production without altering protein sequence. Here we describe deletion and mutagenesis experiments with a dual luciferase reporter to show that the effect the sequence between stems 1 and 2 has on frameshifting efficiency is due to structural changes those mutations cause in the pseudoknot. Similar to previously described viruses containing mutations in the slippery site of the frameshift signal [7] , here we show that mutations to the SARS-CoV frameshift stimulating mRNA pseudoknot can also affect the production of viral genomic RNA. cache = ./cache/cord-253282-zwl0safn.txt txt = ./txt/cord-253282-zwl0safn.txt === reduce.pl bib === id = cord-257052-cik2wmlk author = Ban, Junsu title = Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling date = 2018-12-14 pages = extension = .txt mime = text/plain words = 3885 sentences = 215 flesch = 43 summary = title: Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling. Ectopically expressed NS1 inhibited interferon-β promoter activity that was induced by RIG-IN as determined by the luciferase assays in HEK293T cells, confirming that NS1 itself is capable of inhibiting RIG-I-mediated antiviral signaling ( Figure 1A ). Ectopically expressed NS1 inhibited interferon-β promoter activity that was induced by RIG-IN as determined by the luciferase assays in HEK293T cells, confirming that NS1 itself is capable of inhibiting RIG-I-mediated antiviral signaling ( Figure 1A ). These results suggest that RSV NS1 expression diminishes the interaction between RIG-I and MAVS by interfering with TRIM25-mediated RIG-I ubiquitination. These results indicate that inhibition of TRIM25-mediated RIG-I ubiquitination by NS1 contributes to the suppression of RIG-I signaling, at least in part. cache = ./cache/cord-257052-cik2wmlk.txt txt = ./txt/cord-257052-cik2wmlk.txt === reduce.pl bib === id = cord-267733-fuz8r3vj author = Al Ali, Sally title = Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors date = 2016-05-21 pages = extension = .txt mime = text/plain words = 7966 sentences = 392 flesch = 41 summary = This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost in comparison to other production systems [21, 24] . This reporter gene system has been widely used in transgenic plants, and it has also been successfully used in mammalian cells for VACV recombinant virus selection [54] . Reporter-gene assays have helped the pox virologists in basic research, for example for the study of the location, structure and function of many VACV proteins during the infection cycle and their interaction with proteins of the host cell [44, 70] . The main limitation of using VACV as a vector is the short-term gene expression, since it is a lytic virus killing the infected cells. Insertion sites for recombinant vaccinia virus construction: Effects on expression of a foreign protein cache = ./cache/cord-267733-fuz8r3vj.txt txt = ./txt/cord-267733-fuz8r3vj.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-260431-eksl7pp8 author = Sun, Heting title = Isolation and Identification of Feline Herpesvirus Type 1 from a South China Tiger in China date = 2014-02-28 pages = extension = .txt mime = text/plain words = 2523 sentences = 140 flesch = 55 summary = In the present study, we used molecular methods, virus isolation, TEM examination and an animal challenge experiment to diagnose the cause of death of the South China tiger, and for the first time, we confirmed the infection with FHV-1 in the captive tiger population in China. The phylogenetic tree based on the TK gene sequences showed that the isolate investigated in this study, was closely related to the ten isolates of FHV-1 ( Figure 2 ), a result consistent with the alignment analysis. By PCR/RT-PCR, the only virus detected in the trachea homogenates was FHV-1, which was confirmed afterwards by virus isolation, the TEM examination of cell cultures showing CPE, and a challenge experiment in cats. In this study, the authors described the first occurrence of feline herpesvirus type 1 (FHV-1) in a South China tiger in China. cache = ./cache/cord-260431-eksl7pp8.txt txt = ./txt/cord-260431-eksl7pp8.txt === reduce.pl bib === id = cord-256713-tlluxd11 author = Welch, David title = Is Network Clustering Detectable in Transmission Trees? date = 2011-06-03 pages = extension = .txt mime = text/plain words = 5841 sentences = 306 flesch = 57 summary = [15] show that for a class of networks known as random intersection graphs in which individuals belong to one or more overlapping groups and groups form fully connected cliques, an increase in clustering reduces the epidemic threshold, that is, major outbreaks may occur at lower levels of transmissibility in highly clustered networks. They demonstrate that a rewiring of random intersection graphs that preserves the degree sequence but decreases clustering produces networks with similarly lowered epidemic thresholds and even smaller mean outbreak sizes. From a statistical point of view, these results indicate that even with full data from a particular epidemic outbreak, such as complete knowledge of the transmission tree, it is unlikely that the level of clustering in the underlying contact network could be accurately inferred independently of the degree distribution. cache = ./cache/cord-256713-tlluxd11.txt txt = ./txt/cord-256713-tlluxd11.txt === reduce.pl bib === id = cord-262499-68vmdqky author = Bordi, Licia title = Frequency and Duration of SARS-CoV-2 Shedding in Oral Fluid Samples Assessed by a Modified Commercial Rapid Molecular Assay date = 2020-10-20 pages = extension = .txt mime = text/plain words = 5037 sentences = 311 flesch = 56 summary = We evaluated the use of commercial Simplexa™ COVID-19 Direct assay on OF samples from hospitalized COVID-19 patients, for identification of SARS-CoV-2 RNA, duration of viral shedding, and determining the assay specificity and sensitivity on OF samples compared to NPS and BAL samples. The first performance evaluation on clinical specimen was done by testing 41 consecutive OF samples, including 9 samples from SARS-CoV-2-negative patients, with the Simplexa™ COVID-19 Direct assay and comparing results with that obtained using RT-PCR method established by Corman VM. The performance of Simplexa™ COVID-19 Direct assays on clinical specimens was further established by testing in parallel NPS and OF samples for the presence of SARS-CoV-2 RNA. The performance of Simplexa™ COVID-19 Direct assays on clinical specimens was further established by testing in parallel NPS and OF samples for the presence of SARS-CoV-2 RNA. Second, results from testing on paired OF, NPS and BAL samples by Simplexa™ COVID-19 Direct assay showed almost perfect concordance for virus detection, and high correlation of Ct values. cache = ./cache/cord-262499-68vmdqky.txt txt = ./txt/cord-262499-68vmdqky.txt === 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-013178-li1x1m25 author = Hung, Ling-Chu title = The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells date = 2020-08-29 pages = extension = .txt mime = text/plain words = 9764 sentences = 534 flesch = 59 summary = title: The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells The purpose of this study in the context of the open reading frame 3 (ORF3) protein of porcine circovirus type 2 (PCV2) was especially its location and its relation to the capsid protein and the apoptosis protein in PCV2-infected porcine peripheral blood mononuclear cells (PBMCs). The mAb 7D3 binds to the ORF3 peptide (residues 35–66) and the native ORF3 protein in PCV2-infected PBMCs, as shown by immunofluorescence assay (IFA). Overall, this study provides a blueprint to explore the ORF3 protein in PCV2-infected PBMCs. The Porcine circovirus (PCV) is a small virus and contains closed circular single-stranded DNA [1] . For these purposes, this study used the commercial capsid antigen-ELISA and homemade ORF3 protein-ELISA (anti-N1 polyclonal antibodies and mAb 7D3 based) to detect viral proteins in pig blood. cache = ./cache/cord-013178-li1x1m25.txt txt = ./txt/cord-013178-li1x1m25.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-272459-w14finxf author = Heaton, Nicholas S. title = Dengue Virus and Autophagy date = 2011-08-04 pages = extension = .txt mime = text/plain words = 3107 sentences = 182 flesch = 40 summary = Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. Relevant to DENV infection, a type of selective autophagy termed lipophagy was described, wherein autophagosomes can target cellular stores of lipids known as lipid droplets (LDs) to generate energy for the cell [38] . In subsequent work, the authors reproduced the published results that DENV induces and requires autophagy for robust viral replication [39] . These autophagosomes did not co-localize with markers of the viral replication complex, suggesting that they may play an indirect, non-structural role in DENV replication. Alternatively, DENV infection induces a selective autophagy that is preferentially targeted to lipid droplets, which leads to changes in cellular metabolism. More work, however, is required to show whether the proposed viral triggers of autophagy reproduce all cellular signals and phenotypes that accompany autophagy induction in DENV-infected cells. cache = ./cache/cord-272459-w14finxf.txt txt = ./txt/cord-272459-w14finxf.txt === reduce.pl bib === === reduce.pl bib === id = cord-273366-xd84f8ct author = Brownsword, Matthew J. title = Infectious Bronchitis Virus Regulates Cellular Stress Granule Signaling date = 2020-05-14 pages = extension = .txt mime = text/plain words = 8910 sentences = 520 flesch = 47 summary = Interestingly, we found that IBV is able to inhibit multiple cellular stress granule signaling pathways, whilst at the same time, IBV replication also results in the induction of seemingly canonical stress granules in a proportion of infected cells. Moreover, IBV infection uncouples translational repression and stress granule formation and both processes are independent of eIF2α phosphorylation. Vero cells were infected with IBV and at the indicated time points, cells were fixed and labelled with anti-dsRNA to detect virus infection and with anti-G3BP1 to detect SG. Following identification of SG in IBV infected cells, the requirement for active virus replication in induction of granules was assessed. At 24 hpi, cells were fixed and labelled with anti-G3BP1 (red) to detect stress granules (SG) and IBV infected cells were detected with an anti-dsRNA antibody (green). Junin virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eIF2alpha phosphorylation cache = ./cache/cord-273366-xd84f8ct.txt txt = ./txt/cord-273366-xd84f8ct.txt === reduce.pl bib === id = cord-281552-zfjy3m3i author = Alsaadi, Entedar A. J. title = Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus date = 2020-09-22 pages = extension = .txt mime = text/plain words = 4781 sentences = 205 flesch = 49 summary = Here, we test E-derived peptides for membrane binding activity in vitro and confirm those identified as positive in the context of the full length protein expressed in two different cell types. Relative densitometry of the HSP and LSP bands revealed significant differences among the mutants with regard to their localisation to the different membrane fractions of E expressing insect cells ( Figure 5B ) and confirmed a role for the amphipathic MHV CoV E 50-64 peptide in membrane interaction. An amphipathic helix, EPTM, detected in the post-TM region of E, was suggested by bioinformatics analysis and assessed for direct membrane interaction in vitro by binding to GUVs. For comparison, the predicted E protein TM domain, ETM, and an established membrane active peptide from the influenza M2 protein were also included. Following expression of the complete E protein with mutations in the same identified peptide, altered membrane binding in two distinct cell types, mammalian and insect, was apparent. cache = ./cache/cord-281552-zfjy3m3i.txt txt = ./txt/cord-281552-zfjy3m3i.txt === reduce.pl bib === id = cord-281837-knswbb2d author = Chang, Chia-Wen title = Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry date = 2012-04-11 pages = extension = .txt mime = text/plain words = 4915 sentences = 293 flesch = 57 summary = An assay to measure the inhibition of virus-induced cell death in RD cells was first employed using 1 mg/mL of herbal extracts followed by EC 50 determination if the candidates possessed antiviral activity from the primary screening. DGFW but not DMSO protected the cells from virus-induced CPE (panel E versus F, Figure 2 ), indicating that DGFW inhibited viral replication. To test the mechanism of inhibition of viral entry into host cells by DGFW, we performed attachment and penetration assays. Unbound DGFW was removed, the cells were then infected with EV71 for 1 h, and the progeny viruses in the cells and culture medium were harvested for plaque assay at 10 h p.i. Similarly, EV71 was pretreated with DGFW or DMSO for 30 min at 37 °C, and the infectivity of the treated virus was then determined by plaque assay (Figure 6 ). A neutralization assay (EC 50 ) was used to test the antiviral efficacy of extracts or compounds by measuring the inhibition of CPE induced by enterovirus on RD cells. cache = ./cache/cord-281837-knswbb2d.txt txt = ./txt/cord-281837-knswbb2d.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-272010-kc0gi3cj author = Anand, Sai Priya title = Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins date = 2020-09-29 pages = extension = .txt mime = text/plain words = 3661 sentences = 216 flesch = 56 summary = The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. One potential therapeutic target receiving significant attention is the interaction between the SARS-CoV-2 spike (S) glycoprotein and its receptor, human angiotensin-converting enzyme 2 (ACE2). To better understand the interactions between membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins with their receptor, human ACE2, we sought to determine the cooperativity of ACE2 within the respective trimers. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2 cache = ./cache/cord-272010-kc0gi3cj.txt txt = ./txt/cord-272010-kc0gi3cj.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === 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 pages = extension = .txt mime = text/plain words = 4090 sentences = 202 flesch = 34 summary = 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. Some nucleoside analog drugs targeting specific viral polymerases (acyclovir for herpesviruses, zidovudine for human immunodeficiency virus (HIV), and sofosbuvir for hepatitis C virus (HCV)) have been successful in clinical trials [2] [3] [4] [5] and are currently in use for the treatment of virus-infected patients. However, in recent years, the antiviral activity of gemcitabine has also been reported against a broad range of RNA viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), HCV, poliovirus (PV), influenza A virus (IAV), HIV, and enteroviruses (EV) [13] [14] [15] [16] [17] [18] . Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion cache = ./cache/cord-270103-g9a72xf6.txt txt = ./txt/cord-270103-g9a72xf6.txt === reduce.pl bib === === reduce.pl bib === id = cord-273326-gmw8gl2r author = Saiz, Juan-Carlos title = Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus date = 2018-08-24 pages = extension = .txt mime = text/plain words = 7111 sentences = 293 flesch = 34 summary = In this line, and contrary to above mentioned report [73] , CQ, an FDA-approved anti-inflammatory 4-aminoquinoline and an autophagy inhibitor widely used as an anti-malaria drug that is administered to pregnant women at risk of exposure to Plasmodium parasites, was shown to have anti-ZIKV activity in different cell types (Vero cells, human brain microvascular endothelial cells (hBMECs), and human neural stem cells (NSCs)), affecting early stages of the viral life cycle, possibly by raising the endosomal pH and inhibiting the fusion of the envelope protein to the endosomal membrane [74, 75] . Similarly, by using a drug repurposing screening of over 6000 molecules, it was found that emricasan, a pan-caspase inhibitor that restrains ZIKV-induced increases in caspase-3 activity and is currently in phase 2 clinical trials in chronic hepatitis C virus (HCV)-infected patients, protected human cortical neural progenitor cells (NPC) in both monolayer and three-dimensional organoid cultures, showing neuroprotective activity without suppression of viral replication [82] . cache = ./cache/cord-273326-gmw8gl2r.txt txt = ./txt/cord-273326-gmw8gl2r.txt === reduce.pl bib === === reduce.pl bib === id = cord-283756-ycjzitlk author = Simons, Robin R. L. title = Potential for Introduction of Bat-Borne Zoonotic Viruses into the EU: A Review date = 2014-05-16 pages = extension = .txt mime = text/plain words = 14415 sentences = 605 flesch = 53 summary = Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. Bats are known to have varying degrees of contact with domestic animals and commercial food crops [20, 21] , in particular contact of Pteropus giganteus bats with date palm sap producing trees in Bangladesh is considered a risk factor for human NiV infection [22] . It can be seen that while recent human infections of both NiV and MARV appear to be limited in geographical range (the red areas in Figure 2 ), there are a number of countries where bats have been identified as having the virus, but no human infection has been reported. cache = ./cache/cord-283756-ycjzitlk.txt txt = ./txt/cord-283756-ycjzitlk.txt === reduce.pl bib === id = cord-285935-5rsk6g7l author = Kinast, Volker title = Hepatitis E Virus Drug Development date = 2019-05-28 pages = extension = .txt mime = text/plain words = 6638 sentences = 364 flesch = 46 summary = Cyclic peptides (CP) that had been developed to abrogate interaction of p6Gag and TSG101 and inhibited viral release of HIV Virus like particles (VLPs) [76] were tested for their activity against HEV [77] . The compounds RBV and mycophenolic acid (MPA), both of which target enzymes involved in nucleotide synthesis, are either already used as treatment against HEV or have been reported for their potential to inhibit the virus. So far, the antiviral activity against HEV of only four drugs (Sofosbuvir, pegIFN-α, Ribavirin and silvestrol) was approved in experimental settings beyond in vitro cell culture systems. Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin Sofosbuvir shows antiviral activity in a patient with chronic hepatitis E virus infection Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo cache = ./cache/cord-285935-5rsk6g7l.txt txt = ./txt/cord-285935-5rsk6g7l.txt === reduce.pl bib === id = cord-287647-0nyquokt author = Nemoto, Manabu title = The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland date = 2019-10-14 pages = extension = .txt mime = text/plain words = 2715 sentences = 139 flesch = 57 summary = The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. In contrast in Japan, although an outbreak of diarrhoea occurred among ECoV-infected draft horses at one racecourse [4] [5] [6] , there have been no similar outbreaks subsequently, and all rectal swabs collected from diarrheic Thoroughbred foals were negative. Furthermore, only 2.5% of the rectal swabs collected from healthy foals in the largest Thoroughbred horse breeding region in Japan were positive for ECoV [13] . This study provides the first report of ECoV circulating in Ireland, the third European country with a significant horse industry where the virus has been detected in horses with enteric disease. This is the first report of ECoV detection in faeces samples from both foals and adult horses in Ireland. Low prevalence of equine coronavirus in foals in the largest Thoroughbred horse breeding region of Japan cache = ./cache/cord-287647-0nyquokt.txt txt = ./txt/cord-287647-0nyquokt.txt === reduce.pl bib === id = cord-288556-o8i6j3b2 author = Li, Yanpeng title = Virome of a Feline Outbreak of Diarrhea and Vomiting Includes Bocaviruses and a Novel Chapparvovirus date = 2020-05-04 pages = extension = .txt mime = text/plain words = 5872 sentences = 325 flesch = 53 summary = We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and identified three different feline bocaviruses shed by 9/17 cats. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease. Here, we analyzed a multi-facility outbreak of vomiting and diarrhea in cats using the following approaches: a commercial feline diarrhea panel of PCR tests for known enteric pathogens; viral metagenomics; and follow-up PCRs. Multiple mammalian viruses of varied origins were detected. DNA was extracted from each individual fecal sample (and one pool of 3, cat#973-975) shown in Table 3 plus 4 vomit samples using the QIAamp MinElute Virus Spin Kit (Qiagen, Hilden, Germany), and PCR assays were used for the detection of different viral nucleic acids in each sample. cache = ./cache/cord-288556-o8i6j3b2.txt txt = ./txt/cord-288556-o8i6j3b2.txt === reduce.pl bib === id = cord-289273-zpyz1krq author = Barry, Michele title = Poxvirus Exploitation of the Ubiquitin-Proteasome System date = 2010-10-19 pages = extension = .txt mime = text/plain words = 7212 sentences = 404 flesch = 44 summary = Members of the poxvirus family have recently been shown to encode BTB/kelch and ankyrin/F-box proteins that interact with cullin-3 and cullin-1 based ubiquitin ligases, respectively. Recently, cellular BTB domain-containing proteins have been shown to function as substrate-specific adaptors of cullin-3 based ubiquitin ligase to target proteins for ubiquitination [54] [55] [56] [57] . Although the poxviral ankyrin repeat proteins contain no obvious structural domains at their C-termini, many of the proteins display a conserved sequence, which upon closer inspection was shown to resemble the F-box domain that functions in the recruitment of substrates to the cellular SCF (Skp-1, cullin, F-box) ubiquitin ligase complex [82] [83] [84] . The complex consists of cullin-1, which serves as the molecular scaffold, Roc1, a RING finger ubiquitin ligase, Skp1, the linker protein, and one of over 70 known cellular F-box proteins which function in substrate recruitment ( Figure 2D ) [84] [85] [86] . cache = ./cache/cord-289273-zpyz1krq.txt txt = ./txt/cord-289273-zpyz1krq.txt === reduce.pl bib === id = cord-286343-s8n1ldol author = Martin, Javier title = Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic date = 2020-10-09 pages = extension = .txt mime = text/plain words = 5925 sentences = 340 flesch = 53 summary = We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations. However, it was clear that there was a large reduction of SARS-CoV-2 RNA concentration in sewage between 14th April and 12th May. Positive and negative results were independently confirmed using a second real-time PCR platform (Stratagene 3000P) in a different NIBSC laboratory. However, it was clear that there was a large reduction of SARS-CoV-2 RNA concentration in sewage between 14th April and 12th May. Positive and negative results were independently confirmed using a second real-time PCR platform (Stratagene 3000P) in a different NIBSC laboratory (data not shown). cache = ./cache/cord-286343-s8n1ldol.txt txt = ./txt/cord-286343-s8n1ldol.txt === reduce.pl bib === id = cord-288058-oilurica author = Cui, Tingting title = Role of Porcine Aminopeptidase N and Sialic Acids in Porcine Coronavirus Infections in Primary Porcine Enterocytes date = 2020-04-05 pages = extension = .txt mime = text/plain words = 7087 sentences = 331 flesch = 52 summary = To determine the effect of APN on coronavirus replication, the enterocytes were precultured with 1µg/mL hydrocortisone, 50 µM spermidine, 1 µg/mL insulin, 0.1 µM Wnt agonist, or 1% intestinal contents for 24 h prior to inoculation with PEDV CV777 Vero adapted strain, CV777 fecal suspension, and TGEV Miller. To determine the effect of APN on coronavirus replication, the enterocytes were precultured with 1µg/mL hydrocortisone, 50 µM spermidine, 1 µg/mL insulin, 0.1 µM Wnt agonist, or 1% intestinal contents for 24 h prior to inoculation with PEDV CV777 Vero adapted strain, CV777 fecal suspension, and TGEV Miller. The results show that pretreatment of primary enterocytes with hydrocortisone, spermidine, porcine insulin, Wnt agonist, and intestinal contents could stimulate the expression of APN and enhance the infection of PEDV CV777 Vero adapted and non-adapted strains and the TGEV Miller in the enterocytes. cache = ./cache/cord-288058-oilurica.txt txt = ./txt/cord-288058-oilurica.txt === reduce.pl bib === id = cord-292364-jhiimglg author = Hayakawa, Jun title = Genetic and Antigenic Characterization and Retrospective Surveillance of Bovine Influenza D Viruses Identified in Hokkaido, Japan from 2018 to 2020 date = 2020-08-11 pages = extension = .txt mime = text/plain words = 4375 sentences = 208 flesch = 49 summary = Comparative and phylogenetic analyses using sequence data of the three BIDVs and IDVs from Japan and other countries available in GenBank demonstrated that Japanese BIDVs, including the three BIDV isolates, were genetically distinct from other IDVs. Genotype classifications based on the rotavirus genotype classification revealed multiple genotypes of RNA segments 1–7. Our findings suggest that BIDVs of different genotypes and antigenicity are distributed and maintained in Hokkaido and provide new insights into molecular characteristics and the evolution of IDVs. Influenza viruses are enveloped, segmented, single-stranded, negative-sense RNA viruses, which belong to the family Orthomyxoviridae, and are currently classified into the following four species: influenza A, B, C, and D (IAV-IDV). Viral neutralizing antibody titers of serum samples collected in the acute (pre) and recovery (post) phases of BRD outbreaks that occurred at farms A and B against bovine influenza D viruses (HKD1 and HKD2) isolated from the two farms, as measured using a neutralization assay. cache = ./cache/cord-292364-jhiimglg.txt txt = ./txt/cord-292364-jhiimglg.txt === reduce.pl bib === id = cord-289757-jtvpfsiu author = Abrams, Anna title = The Prevalence and Significance of HTLV-I/II Seroindeterminate Western Blot Patterns date = 2011-08-02 pages = extension = .txt mime = text/plain words = 3490 sentences = 161 flesch = 42 summary = Interestingly, when DNA isolated from peripheral blood mononuclear cells (PBMC) of these HTLV-I/II seroindeterminate individuals is amplified using polymerase chain reaction (PCR) assays, typically no HTLV-I or HTLV-II virus is detected (however, recent reports from Iran, Argentina, and Brazil have challenged this finding) [17] . Enhanced specificity of truncated transmembrane protein for serologic confirmation of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections by western blot (immunoblot) assay containing recombinant envelope glycoproteins Serological, epidemiological, and molecular differences between human T-cell lymphotropic virus Type 1 (HTLV-1)-seropositive healthy carriers and persons with HTLV-I Gag indeterminate Western blot patterns from the Caribbean Molecular analysis of human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) seroindeterminate blood donors from Northeast Iran: Evidence of proviral tax, env, and gag sequences cache = ./cache/cord-289757-jtvpfsiu.txt txt = ./txt/cord-289757-jtvpfsiu.txt === reduce.pl bib === id = cord-295044-eva0soja author = Hutson, Christina L. title = Monkeypox Virus Infections in Small Animal Models for Evaluation of Anti-Poxvirus Agents date = 2010-12-20 pages = extension = .txt mime = text/plain words = 4656 sentences = 223 flesch = 52 summary = The disease pathogenesis has been conjectured and modeled largely from animal studies; initial models were using ectromelia infection of mice; some kinetic observations of virus shedding and viremia have been made in human studies of smallpox and monkeypox. challenged adult common squirrels (Sciurus vulgaris) with 10 6 pfu of MPXV Z-249 (Congo Basin clade) via IN, oral or scarification routes of infection [9] . A follow-up study found the LD 50 for the prairie dog MPXV model is approximately a hundred-times lower for the Congo Basin clade compared to the West African clade (5.9 × 10 3 and 1.29 × 10 5 , respectively) [15] , utilizing an IN route of infection. A prairie dog animal model of systemic orthopoxvirus disease using West African and Congo Basin strains of monkeypox virus Dosage comparison of Congo Basin and West African strains of monkeypox virus using a prairie dog animal model of systemic orthopoxvirus disease cache = ./cache/cord-295044-eva0soja.txt txt = ./txt/cord-295044-eva0soja.txt === reduce.pl bib === id = cord-294347-axkdf5vu author = Kim, Shin-Hee title = Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines date = 2016-07-04 pages = extension = .txt mime = text/plain words = 7189 sentences = 353 flesch = 44 summary = Specifically, vectored vaccines can have advantages for (i) viruses for which a live attenuated vaccine might not be feasible (i.e., HIV); (ii) viruses that do not grow well in vitro (i.e., human papillomavirus, hepatitis C virus, and norovirus); (iii) highly pathogenic viruses that present safety challenges during vaccine development (i.e., SARS-CoV and Ebola virus); (iv) viruses that lose infectivity due to physical instability (i.e., respiratory syncytial virus (RSV)); and (v) viruses that can exchange genes with circulating viruses (i.e., coronaviruses, influenza viruses, and enteroviruses) [4] . Further, immunized mice by the intravenous route were completely protected against a lethal dose of influenza virus, suggesting that NDV can be a safe and effective vaccine vector for possible use in mammalian and avian species. Immunization of primates with a Newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus cache = ./cache/cord-294347-axkdf5vu.txt txt = ./txt/cord-294347-axkdf5vu.txt === reduce.pl bib === id = cord-296736-jsm6o5pq author = Chidlow, Glenys R. title = An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens date = 2009-06-08 pages = extension = .txt mime = text/plain words = 4131 sentences = 183 flesch = 43 summary = title: An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens The aim of this study was to modify real-time PCR assays to facilitate the rapid screening of respiratory samples for a comprehensive range of viral and bacterial pathogens. This tandem multiplex real-time PCR assay, in combination with the semi-nested picornavirus and human metapneumovirus PCR assays, tests for 35 respiratory agents from a sample volume of 180µL compared to 720 µL required for the individual assays. Further work is planned to incorporate the picornavirus and human metapneumovirus assays into the tandem multiplex real-time PCR assay, but so far we have been unable to design or use published real-time PCR primers and probes that detect all types of these viruses with the same sensitivity as our nested assays. A tandem multiplex real-time assay is presented which detects a comprehensive range of respiratory pathogens from a specimen sample of 180µL. Multiplex real-time PCR assay for detection of Influenza and human respiratory syncytial viruses cache = ./cache/cord-296736-jsm6o5pq.txt txt = ./txt/cord-296736-jsm6o5pq.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-292050-x3isowrt author = Ackerman, Emily E. title = Network Controllability-Based Prioritization of Candidates for SARS-CoV-2 Drug Repositioning date = 2020-09-26 pages = extension = .txt mime = text/plain words = 6948 sentences = 384 flesch = 44 summary = Based on network topology and controllability, 16 proteins involved in translation, cellular transport, cellular stress, and host immune response are predicted as regulators of the SARS-CoV-2 infected cell. Screenings of experimentally verified SARS-CoV-2 interacting host proteins [7] have elucidated key infection mechanisms which, when compared to drug databases, have predicted a range of possible targets for repurposing. To assess whether the robust controllability classifications of the driver and virus interacting proteins are a result of the network's connectivity structure, a randomization analysis was performed as developed in previous work [11] . The eight critical virus interacting proteins of the HIN become intermittent in the VIN, losing some control over infected network regulation. The eight critical virus interacting proteins of the HIN become intermittent in the VIN, losing some control over infected network regulation. cache = ./cache/cord-292050-x3isowrt.txt txt = ./txt/cord-292050-x3isowrt.txt === reduce.pl bib === id = cord-290127-51ljxy72 author = Al-Kassmy, Jawad title = Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand? date = 2020-08-07 pages = extension = .txt mime = text/plain words = 7368 sentences = 369 flesch = 46 summary = While the S protein is by far the most studied region for vaccine designs, in silico analyses of potential immunogenic epitopes in the SARS-CoV-2 have suggested several domains within the N, M, and E protein as well as the non-structural proteins primarily focusing on T cell responses [21] [22] [23] [24] [25] . Looking at SARS, several vaccines using different viral vectors or DNA were able to induce high levels of neutralizing antibodies using the full-length S protein, which, in some models, provided protection against challenge [36] [37] [38] [39] [40] . When comparing different vaccine platforms, one study looked at the inactivated vaccines and adenovirus vectors expressing the S protein, or the N protein of SARS reported increased protection when utilizing the whole inactivated virus. A Phase I/II, randomized, placebo-controlled, observer-blind, dose-finding trial in the United States (NCT04368728/NCT04380701) is evaluating the safety, tolerability, immunogenicity, and efficacy of four SARS-CoV-2 RNA vaccine candidates (BNT162a1, BNT162b1, BNT162b2, and BNT162c2) in healthy adults between 18 and 85 years old. cache = ./cache/cord-290127-51ljxy72.txt txt = ./txt/cord-290127-51ljxy72.txt === reduce.pl bib === id = cord-292948-1n5ej08f author = Masse, Shirley title = Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014–2020) in France date = 2020-06-10 pages = extension = .txt mime = text/plain words = 3875 sentences = 209 flesch = 54 summary = title: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014–2020) in France Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs. Coronaviruses (CoVs) are an enveloped, single positive-strand RNA species of viruses belonging to the Coronaviridae family, which infect birds and mammals. Here, we document the epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) observed in general practice. To study the weekly number of HCoVs detected among ILI/ARI patients seen in general practice during the six influenza seasons, we gathered all samples collected by GPs for influenza surveillance and for the IRIIS study (Table 1 and Figure 1 ). cache = ./cache/cord-292948-1n5ej08f.txt txt = ./txt/cord-292948-1n5ej08f.txt === reduce.pl bib === id = cord-295750-0gpyi4ii author = Raev, Sergei title = An Outbreak of a Respiratory Disorder at a Russian Swine Farm Associated with the Co-Circulation of PRRSV1 and PRRSV2 date = 2020-10-15 pages = extension = .txt mime = text/plain words = 2937 sentences = 331 flesch = 59 summary = A partial open reading frame 7 sequence of the PRRSV2 isolate demonstrated a high identity with modified live vaccine-related strains from Denmark (93%) and wild-type VR2332 (92%). PRRSV, PCV2, swine influenza virus (SIV), porcine parvovirus virus (PPV), and porcine respiratory coronavirus (PRCV) in serum samples were detected using commercial polymerase chain reaction (PCR) kits (Vetbiochem, Russia) according to the manufacturer's instructions. Phylogenetic analysis of a partial ORF7 sequence of the PRRSV2 strain isolated in the course of this study revealed that this strain was very dissimilar (88% identity) to the only known PRRSV2 strain (JXA1-related, sublineage 8.7) detected in East Siberia, Russia, in 2007. Comparison of Molecular and Biological Characteristics of a Modified Live Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Vaccine (Ingelvac PRRS MLV), the Parent Strain of the Vaccine (ATCC VR2332), ATCC VR2385, and Two Recent Field Isolates of PRRSV Genetic Analysis of ORF5 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Isolated in Vietnam cache = ./cache/cord-295750-0gpyi4ii.txt txt = ./txt/cord-295750-0gpyi4ii.txt === reduce.pl bib === id = cord-294842-aesiff1f author = Romero-Brey, Inés title = Membranous Replication Factories Induced by Plus-Strand RNA Viruses date = 2014-07-22 pages = extension = .txt mime = text/plain words = 11038 sentences = 520 flesch = 40 summary = Three-dimensional reconstructions of the WNV KUN replication sites revealed an intimate association of the rough ER (rER) with the bounding membrane of the VPs [20] (Figure 2B ), resembling the vesicles observed in DENV-infected cells. In cells infected with TBEV, one of the most important tick-transmitted viruses in Europe and Asia, virus particles and membrane-connected vesicles were also observed inside the ER [25] , similar to what was described for DENV and WNV KUN . Importantly, pulse-radiolabeling experiments localized sites of active RNA replication to the outer surface of single-membrane tubules [71] and isolation of the membranous replication factories and their subsequent visualization by EM revealed that they form rosette-like structures composed of virus-induced cytoplasmic vesicles [124] . Formation of plant RNA virus replication complexes on membranes: Role of an endoplasmic reticulum-targeted viral protein cache = ./cache/cord-294842-aesiff1f.txt txt = ./txt/cord-294842-aesiff1f.txt === reduce.pl bib === id = cord-295433-olmein3q author = Banerjee, Arinjay title = Bats and Coronaviruses date = 2019-01-09 pages = extension = .txt mime = text/plain words = 5655 sentences = 298 flesch = 52 summary = Initial studies investigating animal sources of the virus from "wet markets" in the Guangdong province of China suggested that Himalayan palm civets and raccoon dogs were the most likely hosts responsible for human transmission [22] ; however, the role of bats as the original animal reservoir hosts of SARS-CoV was speculated as similar viruses were detected in them [27, 28] . A recent study found that 16 out of 30 camel workers surveyed in Saudi Arabia show evidence of prior MERS-CoV infection via seroconversion and/or virus-specific CD8+ T cell responses without any history of significant respiratory disease. The primary bat species being used to study the bat immune response to virus infections in vitro and in vivo are Pteropus alecto (black flying fox), Rousettus aegyptiacus (Egyptian rousette), and Artibeus jamaicensis (Jamaican fruit bat). Multiple studies with PEDV, SARS-and MERS-CoVs have identified accessory proteins that can effectively inhibit an IFN response in mammalian cells [12] [13] [14] [91] [92] [93] [94] [95] . cache = ./cache/cord-295433-olmein3q.txt txt = ./txt/cord-295433-olmein3q.txt === reduce.pl bib === id = cord-297092-oq14cwka author = Tan, Shaoyuan title = Characterization of Emerging Swine Viral Diseases through Oxford Nanopore Sequencing Using Senecavirus A as a Model date = 2020-10-07 pages = extension = .txt mime = text/plain words = 6982 sentences = 332 flesch = 53 summary = This study developed whole genome sequencing methods to facilitate the control of SVA and provide a reference for the timely detection and prevention of other emerging infectious diseases. For the sequencing of cell culture samples, raw pass reads were mapped to the SVA reference genome (GenBank: MN164664) using Minimap2 [34] , then analyzed using Qualimap [35] , generating raw error rates and coverage information which was then visualized using GraphPad prism software (GraphPad Software, San Diego, CA, USA). After determining the consensus generation strategies for both sequencing methods, optimization was performed in terms of total input sequencing yield and the pre-treatment of raw reads using the cell culture virus in which the whole genome sequence was already known. In order to evaluate and compare the general performance of DRS and PCS for viral whole genome recovery, two whole genome sequencing runs using a cell culture-grown virus with a known reference sequence were carried out for each method (Table 1 ). cache = ./cache/cord-297092-oq14cwka.txt txt = ./txt/cord-297092-oq14cwka.txt === reduce.pl bib === id = cord-296819-gztmidn2 author = Sambri, Vittorio title = Diagnosis of West Nile Virus Human Infections: Overview and Proposal of Diagnostic Protocols Considering the Results of External Quality Assessment Studies date = 2013-09-25 pages = extension = .txt mime = text/plain words = 6732 sentences = 304 flesch = 42 summary = title: Diagnosis of West Nile Virus Human Infections: Overview and Proposal of Diagnostic Protocols Considering the Results of External Quality Assessment Studies This paper reviews the presently available methods to achieve the laboratory diagnosis of West Nile virus infections in humans, discussing the most prominent advantages and disadvantages of each in light of the results obtained during four different External Quality Assessment studies carried out by the European Network for 'Imported' Viral Diseases (ENIVD). For the routine detection of WNV RNA using molecular techniques there are two distinct diagnostic settings: the first involves blood and organ donation screening from subjects living in an area where WNV circulation is known to be occurring, and the second involves the identification of viral genomes in serum, plasma and CSF samples from patients presenting with a clinical picture typical of WNV infection [21] . cache = ./cache/cord-296819-gztmidn2.txt txt = ./txt/cord-296819-gztmidn2.txt === reduce.pl bib === id = cord-297339-et2305rz author = Lauber, Chris title = Genetics-Based Classification of Filoviruses Calls for Expanded Sampling of Genomic Sequences date = 2012-08-31 pages = extension = .txt mime = text/plain words = 4480 sentences = 235 flesch = 46 summary = In DEmARC, virus clusters are delimited objectively by devising a universal family-wide threshold on intra-cluster genetic divergence of viruses that is specific for each level of the classification. Based on our experience with other virus families, we conclude that the current sampling of filovirus genomic sequences needs to be considerably expanded in order to resolve these uncertainties in the framework of genetics-based classification. The DEmARC specifics include (i) the use of pairwise evolutionary distances (PEDs) instead of uncorrected p-distances, and (ii) a quantitative method to devise taxon levels and associated PED thresholds for virus clustering in a systematic and family-wide manner. The first selected threshold (PED of 0.120) results in seven clusters ( Figure 1B ) that match the official or tentative ICTV species of the family Filoviridae. In the high-sampling case of picornaviruses, no PED values with zero frequency are observed which suggests that the current sampling of filovirus genome sequences may strongly underestimate the natural genetic diversity in the family. cache = ./cache/cord-297339-et2305rz.txt txt = ./txt/cord-297339-et2305rz.txt === reduce.pl bib === id = cord-300625-fvirvpyl author = Srinivasan, Suhas title = Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins date = 2020-03-25 pages = extension = .txt mime = text/plain words = 5902 sentences = 285 flesch = 41 summary = In addition to the global structural genomics, an initiative that focuses on determining the 3D structures of individual proteins on a genome scale [34] , as well as to the specific efforts aimed at rapid structural characterization of proteins in emerging viruses [35] [36] [37] [38] , multiple works have used comparative modeling to predict the structures of protein-protein interaction complexes [39] [40] [41] , facilitate structure-based drug discovery [33, 42, 43] , infer protein functions [44] , determine the macromolecular interaction network [45] [46] [47] [48] , and provide molecular insights into the viral evolution [49] [50] [51] . To do so, we structurally characterized individual proteins as well as intra-viral and human-virus protein complexes, extracted the information on their interaction interfaces and ligand binding, and superposed the evolutionary difference and conservation information with the binding information. cache = ./cache/cord-300625-fvirvpyl.txt txt = ./txt/cord-300625-fvirvpyl.txt === reduce.pl bib === id = cord-301633-t8s4s0wo author = Gralinski, Lisa E. title = Return of the Coronavirus: 2019-nCoV date = 2020-01-24 pages = extension = .txt mime = text/plain words = 3938 sentences = 186 flesch = 51 summary = Similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infections, patients exhibited symptoms of viral pneumonia including fever, difficulty breathing, and bilateral lung infiltration in the most severe cases [1] . A range of disease has been observed highlighted by fever, dry cough, shortness of breath, and leukopenia; patients have included mild cases needing supportive care to severe cases requiring extracorporeal membrane oxygenation; however, compared to SARS-CoV (10% mortality) and MERS-CoV (35% mortality), the 2019-nCoV appears to be less virulent at this point with the exception of the elderly and those with underlying health conditions. In the early part of the outbreak, the absence of infection in health care workers argued for inefficient human to human spread and distinguished 2019-nCoV from both SARS-CoV and MERS-CoV. cache = ./cache/cord-301633-t8s4s0wo.txt txt = ./txt/cord-301633-t8s4s0wo.txt === reduce.pl bib === id = cord-301810-vtgdqart author = Aston, Emily J. title = Effect of Pullet Vaccination on Development and Longevity of Immunity date = 2019-02-02 pages = extension = .txt mime = text/plain words = 7115 sentences = 321 flesch = 45 summary = Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). At 5 days following challenge with IBV GA98, vaccinated/challenged birds had significantly lower RNA loads compared to positive controls at all collection times and in all tissue samples, with the exception of cecal tonsil at 24 WOA (Table 1 ). ILTV-specific IgG titers in serum collected 5 days post-challenge were significantly higher in vaccinated birds from both challenged and non-challenged groups, compared to the positive and negative controls ( Figure 6 ). ILTV-specific IgG titers in serum collected 5 days post-challenge were significantly higher in vaccinated birds from both challenged and non-challenged groups, compared to the positive and negative controls ( Figure 6 ). cache = ./cache/cord-301810-vtgdqart.txt txt = ./txt/cord-301810-vtgdqart.txt === reduce.pl bib === id = cord-297834-me1ajoyb author = Schountz, Tony title = Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions date = 2014-03-14 pages = extension = .txt mime = text/plain words = 6425 sentences = 334 flesch = 38 summary = The immune response is energetically expensive for wild animals, thus the findings of experimental studies will be critical for understanding the ecoimmunology of reservoir hosts of hantaviruses [6, 7] , and experiments using wild rodents in natural or semi-natural environments [8, 9] will be required to validate laboratory findings. Currently, three laboratory infection systems have been developed to study hantavirus infections of reservoir hosts: Seoul virus (SEOV) infection of the Norway rat (Rattus norvegicus), Puumala virus (PUUV) infection of the bank vole (Myodes glareolus), and Sin Nombre virus (SNV) infection of the deer mouse (Peromyscus maniculatus) [12, 14, 16] . Experimental data have also shown that patterns of the expression of genes related to the immune response are different in infected males and females [32] , and it is likely these differences have important roles in hantavirus ecology. cache = ./cache/cord-297834-me1ajoyb.txt txt = ./txt/cord-297834-me1ajoyb.txt === reduce.pl bib === id = cord-309239-6lso1w0o author = Adney, Danielle R. title = Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding date = 2016-08-19 pages = extension = .txt mime = text/plain words = 2989 sentences = 149 flesch = 50 summary = The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen first described from Saudi Arabia in 2012 [1] that can cause severe respiratory disease and death in roughly 36% of infected humans [2] . There is considerable field and experimental evidence that dromedary camels serve as an important reservoir host involved in transmission to humans [3] [4] [5] [6] [7] [8] , but whether other livestock such as goats, sheep, and horses play a role in transmission has only been assessed indirectly. The objective of this study was to determine if goats, sheep, and horses can be infected with MERS-CoV and assess their potential importance in viral transmission. Sheep, goat kids and horses were each inoculated intranasally with 1.4 × 10 6 to 1.9 × 10 6 plaque-forming units (PFU) of a low passage human isolate of MERS-CoV (strain HCoV-EMC/2012) propagated in Vero E6 cells as described previously [11] . cache = ./cache/cord-309239-6lso1w0o.txt txt = ./txt/cord-309239-6lso1w0o.txt === reduce.pl bib === id = cord-302716-wfla3l20 author = Popov, Vsevolod L. title = Electron Microscopy in Discovery of Novel and Emerging Viruses from the Collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) date = 2019-05-25 pages = extension = .txt mime = text/plain words = 5445 sentences = 318 flesch = 45 summary = Viruses can be differentiated by their specific morphology (ultrastructure): shape, size, intracellular location, or from the ultrastructural cytopathic effects and specific structures forming in the host cell Upolu, Aransas Bay [22] , Sinu [23] , and Trinity [24] orthobunyaviruses [25] [26] [27] , nyamiviruses [28] , a new reovirus from Cameroon (Fako virus) [29] and Colombia [30] , a new paramyxovirus [31] , an insect-specific (capable of replication in insects but not in vertebrates) alphavirus [32] , a new flavivirus genus [33] and other novel flaviviruses [34] [35] [36] [37] and rhabdoviruses [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] . Insect-specific viruses isolated recently from mosquitoes and phlebotomine sandflies have been characterized and proposed to represent a new genus (Negevirus) related to genera of mite-infecting plant viruses (Blunervirus, Cilevirus, and Higrevirus) in the new family Kitaviridae [49, 73] , or novel members of Entomobirnavirus, family Birnaviridae ( Figure 10D ). cache = ./cache/cord-302716-wfla3l20.txt txt = ./txt/cord-302716-wfla3l20.txt === reduce.pl bib === id = cord-306004-amv0los1 author = Widagdo, W. title = Host Determinants of MERS-CoV Transmission and Pathogenesis date = 2019-03-19 pages = extension = .txt mime = text/plain words = 4525 sentences = 242 flesch = 46 summary = Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. MERS-CoV infection in these animals merely causes mild upper respiratory tract infection [17, 18] , but seroepidemiological studies showed that this virus has been circulating in dromedary camels for decades, suggesting the efficient transmission of MERS-CoV in this species [19] [20] [21] [22] . Given the fact that experimental in vivo infection studies and DPP4 expression analysis in different animal species revealed that dromedary camels are not the only animals in which MERS-CoV has an upper respiratory tract tropism [17, 18, 83, 84] , it is then relevant to question whether other animals can potentially spread MERS-CoV as well. cache = ./cache/cord-306004-amv0los1.txt txt = ./txt/cord-306004-amv0los1.txt === reduce.pl bib === id = cord-305857-2409me0p author = López-Roig, Marc title = Seroprevalence Dynamics of European Bat Lyssavirus Type 1 in a Multispecies Bat Colony date = 2014-09-04 pages = extension = .txt mime = text/plain words = 3873 sentences = 207 flesch = 49 summary = In recent years, bats have been implicated in numerous emerging infectious disease events and have been recognized as important reservoir hosts for viruses that can cross the species barrier to infect humans and other domestic and wild mammals [3] . Persistent viral infections occurring among long-lived bats, coupled with their often gregarious roosting behavior, could greatly increase the potential for intra-and inter-species transmission of viruses [7] , especially in summer and winter periods. To study the variation in EBLV-1-antibody prevalence, we conducted two analyses: first, three explanatory variables (sex, species and year) were first screened using a univariate analysis and a chi-square test to check for statistically significant associations with serological status (0: negative; 1: positive). We report the results of the prevalence of specific EBLV-1 neutralizing antibody analysis from the 2004-2012 period in nine bat species roosting in the same refuge. cache = ./cache/cord-305857-2409me0p.txt txt = ./txt/cord-305857-2409me0p.txt === reduce.pl bib === id = cord-307046-ko3bdvo0 author = Vasilakis, Nikos title = Exploiting the Legacy of the Arbovirus Hunters date = 2019-05-23 pages = extension = .txt mime = text/plain words = 17749 sentences = 879 flesch = 44 summary = Complete genome sequences are now available for many of the archived isolates, allowing more accurate taxonomic assignments, analysis of their phylogenetic and evolutionary relationships with other viruses, and evaluation of the potential risks they may present to humans and wild or domestic animal populations. Scientists in these field laboratories were involved in the detection and investigation of human diseases in their respective geographic regions, surveying human and animal populations for serologic evidence of past viral infection, and searching for viruses in a wide variety of arthropods, mammals, birds, reptiles, and amphibians [2] . The family contains several serious human pathogens, including dengue, yellow fever, Zika, Japanese encephalitis, West Nile, and tick-borne encephalitis viruses (all arboviruses in the genus Flavivirus) and the hepatitis C virus (a member of the genus Hepacivirus). cache = ./cache/cord-307046-ko3bdvo0.txt txt = ./txt/cord-307046-ko3bdvo0.txt === reduce.pl bib === id = cord-307110-eiobmxp2 author = Zhao, Shan title = Serological Screening for Coronavirus Infections in Cats date = 2019-08-13 pages = extension = .txt mime = text/plain words = 6732 sentences = 382 flesch = 57 summary = In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Synthetic sequences of 12 coronavirus spike S1 subunits (HCoV-HKU1 (GB: YP_173238.1), MERS-CoV (GB:YP_009047204.1), SARS-CoV (GB: AAX16192.1), HCoV-OC43 (GB: AAR01015.1), HCoV-229E (GB: NP_073551.1), HCoV-NL63 (GB: YP_003767.1), TGEV (GB: ABG89325.1), PEDV (GB: AOG30832.1), BCoV (GB: P15777.1), PDCoV (GB: AML40825.1), FCoV type 1 (GB: FJ938060.1), FCoV type 2 (GB: AY994055.1)) and different domains of PEDV S1 subunit (S1 0 and S1 A-D , as identified and described in [40] ) were cloned into pCAGGS expression plasmids as described previously [41] . cache = ./cache/cord-307110-eiobmxp2.txt txt = ./txt/cord-307110-eiobmxp2.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-309623-2ngr682l author = Han, Xiaoxiao title = Infectious Bronchitis Virus Infection Induces Apoptosis during Replication in Chicken Macrophage HD11 Cells date = 2017-07-26 pages = extension = .txt mime = text/plain words = 5618 sentences = 317 flesch = 46 summary = Previous studies have reported that infectious bronchitis virus (IBV) infection can produce cytopathic effects (CPE) and apoptosis in some mammalian cells and primary cells. The Beaudette strains were used previously to study the resistance of IBV to the antiviral state induced by type I interferon (IFN) [7] , induction of apoptosis through endoplasmic reticulum stress in Vero cells by IBV infection [8] and activate autophagy by IBV nonstructural protein (NSP) 6 [9] . The rate of apoptosis significantly increased at 12 h.p.i. in virus-infected cells when compared with the mockInfection of HD11 cells with IBV Beaudette caused cell death in a time-and dose-dependent manner, as tested by CCK-8 assay. The results also showed that activation of caspase-9 in IBV Beaudette-infected cells was regulated by decreased expression of Bcl-2 and increased expression of Bax. The caspase-3 activation and virus-induced apoptosis might be triggered through both extrinsic and intrinsic pathways. cache = ./cache/cord-309623-2ngr682l.txt txt = ./txt/cord-309623-2ngr682l.txt === reduce.pl bib === id = cord-309635-1tgovkr7 author = Wu, Nicholas C. title = Structural Biology of Influenza Hemagglutinin: An Amaranthine Adventure date = 2020-09-22 pages = extension = .txt mime = text/plain words = 5497 sentences = 289 flesch = 42 summary = Hemagglutinin (HA) glycoprotein is an important focus of influenza research due to its role in antigenic drift and shift, as well as its receptor binding and membrane fusion functions, which are indispensable for viral entry. Similarly, RBS of influenza B HA is composed of the 140-loop, 190-helix, and 240-loop, which are structurally equivalent to the 130-loop, 150-loop, and 190-helix Receptor specificity can also continue to evolve when seasonal viruses circulate in the human population, due to natural mutations that are likely a response to immune selection pressure. A broadly neutralizing human monoclonal antibody that recognizes a conserved, novel epitope on the globular head of the influenza H1N1 virus hemagglutinin Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin Design of nanoparticulate group 2 influenza virus hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages cache = ./cache/cord-309635-1tgovkr7.txt txt = ./txt/cord-309635-1tgovkr7.txt === reduce.pl bib === id = cord-309693-f2htekhz author = Yu, Meiling title = Immunogenicity of eGFP-Marked Recombinant Lactobacillus casei against Transmissible Gastroenteritis Virus and Porcine Epidemic Diarrhea Virus date = 2017-09-25 pages = extension = .txt mime = text/plain words = 5934 sentences = 234 flesch = 45 summary = To develop an effective bivalent oral vaccine against TGEV and PEDV infection, the D antigenic site of the TGEV spike (S) protein and the major antigen site (core neutralizing epitope—COE) of the PEDV S protein were used as immunogens, and the enhanced green fluorescent protein (eGFP) gene was used as a reporter to construct genetically engineered Lactobacillus casei rLpPG(F)-T7g10-eGFP-6D-COE. The results showed that levels of anti-PEDV and anti-TGEV serum immunoglobulin G (IgG) and mucosal secreted immunoglobulin A (sIgA) antibodies obtained from the mice immunized with rLpPG(F)-T7g10-eGFP-6D-COE, as well as the proliferation levels of lymphocytes, were significantly higher than those in mice orally administered phosphate-buffered saline (PBS) or rLpPG-T7g10. This was evidenced by significantly higher levels of virus-neutralizing antibodies, anti-PEDV/TGEV serum IgG, and mucosal sIgA in mice orally immunized with rLpPG F -T7g10-eGFP-6D-COE, compared to the levels for the rLpPG-T7g10 or PBS groups. cache = ./cache/cord-309693-f2htekhz.txt txt = ./txt/cord-309693-f2htekhz.txt === reduce.pl bib === id = cord-310734-6v7oru2l author = Bolatti, Elisa M. title = A Preliminary Study of the Virome of the South American Free-Tailed Bats (Tadarida brasiliensis) and Identification of Two Novel Mammalian Viruses date = 2020-04-09 pages = extension = .txt mime = text/plain words = 8477 sentences = 405 flesch = 41 summary = By conventional nucleic acid detection techniques and/or bioinformatics approaches, the genomes of two novel viruses were completely covered clustering into the Papillomaviridae (Tadarida brasiliensis papillomavirus type 1, TbraPV1) and Genomoviridae (Tadarida brasiliensis gemykibivirus 1, TbGkyV1) families. Overall, a large number of phage-related sequences were detected (77.3% of viral read pairs and 39.9% of viral contigs), likely representing the most abundant entities infecting bacteria present in the bat digestive system, which exhibited similarity mostly to the families Inoviridae, Siphoviridae, and Myoviridae ( Table 1 ). Several mammalian viral families, supported by the contigs and sequencing reads, have been identified previously in New World [23, 24, 26] and Old World [17, 18, 89] bat species. Table S4 : Read pairs and contigs classified as similar to viruses and not taxonomical assigned to viral families identified in anal and oral swab samples of Tadarida brasiliensis obtained by metagenomics using Illumina technology. cache = ./cache/cord-310734-6v7oru2l.txt txt = ./txt/cord-310734-6v7oru2l.txt === reduce.pl bib === id = cord-308201-lavcsqov author = Desforges, Marc title = Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? date = 2019-12-20 pages = extension = .txt mime = text/plain words = 8470 sentences = 473 flesch = 36 summary = Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Even though no clear cause and effect link has ever been made with the onset of human neurological diseases, their neuropathogenicity is being increasingly recognized in humans, as several recent reports associated cases of encephalitis [244] , acute flaccid paralysis [271] and other neurological symptoms, including possible complications of HCoV infection such as Guillain-Barré syndrome or ADEM [249, [272] [273] [274] [275] [276] [277] [278] [279] . Like for several other respiratory viruses, accumulating evidence now indicate that HCoV are neuroinvasive in humans and we hypothesize that these recognized respiratory pathogens are potentially neurovirulent as well, as they could participate in short-and long-term neurological disorders either as a result of inadequate host immune responses and/or viral propagation in the CNS, which directly induces damage to resident cells. cache = ./cache/cord-308201-lavcsqov.txt txt = ./txt/cord-308201-lavcsqov.txt === reduce.pl bib === id = cord-309571-a0xu1d56 author = Aboughdir, Maryam title = Prognostic Value of Cardiovascular Biomarkers in COVID-19: A Review date = 2020-05-11 pages = extension = .txt mime = text/plain words = 5690 sentences = 288 flesch = 47 summary = With intensive care units operating at maximum capacity and such staggering mortality rates reported, it is imperative during this time-sensitive COVID-19 outbreak to identify patients with an increased risk of adverse outcomes and/or myocardial injury. found that myocardial injury, defined by raised serum cardiac troponin I (cTnI) levels, in COVID-19 patients was associated with over 50% mortality rate [12] . In the study by Wang et al., 36 out of 138 (26.1%) COVID-19 patients were admitted to the ICU with severe symptoms, all of whom had significantly elevated serum cTnI and CK-MB levels (p = 0.004 and p < 0.001, respectively) compared to non-ICU patients [11] . cTnI provides remarkable prognostic value for patients at increased risk of worsening outcomes and in-hospital mortality, though studies have also shown the association of raised CK-MB and BNP levels with more severe symptoms of COVID-19. cache = ./cache/cord-309571-a0xu1d56.txt txt = ./txt/cord-309571-a0xu1d56.txt === reduce.pl bib === id = cord-311008-b7xjlqg3 author = Zapatero-Belinchón, Francisco J. title = Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors date = 2019-03-19 pages = extension = .txt mime = text/plain words = 10350 sentences = 556 flesch = 52 summary = Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. The remarkable diversity of plasma membrane proteins implicated in filovirus cell entry prompted us to analyze twelve cell lines for a potential correlation of host factor expression to filovirus susceptibility. We could show that the neuroblastoma SH-SY5Y cell line is specifically resistant to filovirus infection although all intracellular proteins known to be essential were expressed, and although its overall transcriptome was very similar to that of susceptible cell lines. Heterokaryon assays revealed that SH-SY5Y cells did not express a dominant restriction factor that inhibited filovirus GP-driven cell entry, but recombinant GP could not bind to their plasma membrane. In SH-SY5Y cells, however, an ectopic expression of any potential attachment-promoting plasma membrane protein of filoviruses, such as DC-SIGN, Axl, Mer, or TIM-1, conferred susceptibility to filovirus GP-driven transduction or infection. cache = ./cache/cord-311008-b7xjlqg3.txt txt = ./txt/cord-311008-b7xjlqg3.txt === reduce.pl bib === id = cord-310579-tnxokfwu author = Kim, Sung-Jae title = Molecular Characterization of Porcine Epidemic Diarrhea Virus and Its New Genetic Classification Based on the Nucleocapsid Gene date = 2020-07-23 pages = extension = .txt mime = text/plain words = 4887 sentences = 269 flesch = 54 summary = title: Molecular Characterization of Porcine Epidemic Diarrhea Virus and Its New Genetic Classification Based on the Nucleocapsid Gene In the phylogenetic trees inferred from the D1-D2 datasets of the S gene ( Figure 2 , Supplementary Figures S1 and S2) , the PEDV strains were classified into five sub-genogroups (G1a, G1b, G2a, G2b, and G2c), which were previously designated [8] . In the phylogenetic trees inferred from the D1-D2 datasets of the S gene ( Figure 2 , Supplementary Figures S1 and S2) , the PEDV strains were classified into five sub-genogroups (G1a, G1b, G2a, G2b, and G2c), which were previously designated [8] . Supported by high posterior probability values (0.90-1), the phylogenetic trees inferred from the D3-D4 datasets of the N gene (Figure 3, Supplementary Figures S3 and S4) suggested that the classification of PEDV strains into four S gene-based sub-genogroups G1a, G1b, G2b, G2a/G2c was more reliable. Sequence and phylogenetic analysis of nucleocapsid genes of porcine epidemic diarrhea virus (PEDV) strains in China cache = ./cache/cord-310579-tnxokfwu.txt txt = ./txt/cord-310579-tnxokfwu.txt === reduce.pl bib === id = cord-309378-sfr1x0ob author = Röst, Gergely title = Early Phase of the COVID-19 Outbreak in Hungary and Post-Lockdown Scenarios date = 2020-06-30 pages = extension = .txt mime = text/plain words = 10526 sentences = 585 flesch = 57 summary = COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a considerable reduction in the number of contacts and transmission of the virus. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed. Moreover, closing schools postpones the peak of the epidemic (by about one month in case of the above setting), suggesting that children may play a significant role in transmission due to their large number of contacts, even though they give negligible contribution to the overall mortality, cf. As control measures are being successively relaxed since May 4, we established an age-structured compartmental model to investigate several post-lockdown scenarios, and projected the epidemic curves and the demand for critical care beds assuming various levels of sustained reduction in transmission. cache = ./cache/cord-309378-sfr1x0ob.txt txt = ./txt/cord-309378-sfr1x0ob.txt === reduce.pl bib === id = cord-311205-3uwiys4a author = Hung, Yu-Fu title = Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes date = 2015-07-21 pages = extension = .txt mime = text/plain words = 4604 sentences = 231 flesch = 53 summary = In addition, amino acid residues of the central region of some NS4A peptides might bind directly to the liposome leading to the disappearance of the corresponding NMR signals. In addition, amino acid residues of the central region of some NS4A peptides might bind directly to the liposome leading to the disappearance of the corresponding NMR signals. Finally, amino acid residues in the C-terminal region of NS4A(1-48) from T33 to L48 show the smallest reduction in the free state peak intensities upon liposome addition (Figure 2A) . Inspection of HSQC spectra of mutant NS4A(1-48, L6E;M10E) in buffer and with increasing amounts of sonicated POPC liposomes revealed no changes in cross peak positions and only a minor Finally, amino acid residues in the C-terminal region of NS4A(1-48) from T33 to L48 show the smallest reduction in the free state peak intensities upon liposome addition (Figure 2A) . cache = ./cache/cord-311205-3uwiys4a.txt txt = ./txt/cord-311205-3uwiys4a.txt === reduce.pl bib === id = cord-310255-aixq5mhf author = Charlton, Frank W. title = Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives date = 2020-08-03 pages = extension = .txt mime = text/plain words = 5345 sentences = 321 flesch = 46 summary = More recent evidence highlights how viruses can regulate and/or depend on the ion channels expressed by host cells, highlighting them as new host targets for therapeutic intervention (reviewed by Hover et al., 2017) [14] . We then discuss how intracellular ion channels contribute to the Two-pore channels 1 and 2 (TPC1/2) Gunaratne et al., 2018 [34] Severe fever with thrombocytopenia syndrome virus (SFTSV) Unknown channel Li et al., 2019 [35] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Two-pore channel 2 (TPC2) Ou et al., 2020 [36] Bunyamwera orthobunyavirus (BUNV) Two-pore domain K + (K 2P ) Hover et al., 2016/18 [28, 37] Hazara orthonairovirus (HAZV) Unknown K + channel Punch et al., 2017 [38] Charlton et al., 2019 [39] Human immunodeficiency virus (HIV) G-Protein coupled inwardly rectifying K + (GIRK) ATP-sensitive K + K ATP Dubey et al., 2019 [40] Merkel cell polyomavirus (MCPyV) cache = ./cache/cord-310255-aixq5mhf.txt txt = ./txt/cord-310255-aixq5mhf.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 === id = cord-312272-g4n426cm author = Matczuk, Anna Karolina title = Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells date = 2019-08-09 pages = extension = .txt mime = text/plain words = 8453 sentences = 375 flesch = 53 summary = title: Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells To determine whether these results were caused by the emergence of viruses containing mutations, the intracellular RNA was isolated after infection with P7, P10, P15, and P19 EAVGp3-HA virus and subjected to RT-PCR, followed by sequence analysis ( Figure 2C ). To determine whether these results were caused by the emergence of viruses containing mutations, the intracellular RNA was isolated after infection with P7, P10, P15, and P19 EAVGp3-HA virus and subjected to RT-PCR, followed by sequence analysis ( Figure 2C ). We studied the co-localization of the Gp3-HA, E protein, and N protein in EAV-infected BHK-21 cells using immunofluorescence microscopy (18 h p.i.). The tagged Gp3 in the virus context might facilitate research on the biology of EAV, e.g., in this study, we analyzed the localization of the Gp3-HA in the infected cells. cache = ./cache/cord-312272-g4n426cm.txt txt = ./txt/cord-312272-g4n426cm.txt === reduce.pl bib === id = cord-313312-h607itv2 author = Mok, Darren Z. L. title = The Effects of Pre-Existing Antibodies on Live-Attenuated Viral Vaccines date = 2020-05-08 pages = extension = .txt mime = text/plain words = 7417 sentences = 349 flesch = 34 summary = Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. The clinical trial finding that subjects with a limited range of cross-reactive antibodies from a prior Japanese Encephalitis vaccine were able to enhance yellow fever vaccination, by prolonging vaccine viremia duration that leads to higher antibody titers, thus hints at the possibility that whether pre-existing antibodies inhibit or augment flavivirus infection will depend on both antibody titers and the type/specificity of antibodies produced [85] . By contrast, at sub-neutralizing titers, pre-existing antibodies can enable viruses to better infect cells and increase innate immune responses that augment LAV immunogenicity. By contrast, at sub-neutralizing titers, pre-existing antibodies can enable viruses to better infect cells and increase innate immune responses that augment LAV immunogenicity. cache = ./cache/cord-313312-h607itv2.txt txt = ./txt/cord-313312-h607itv2.txt === reduce.pl bib === id = cord-313161-07iwwsfz author = Lundstrom, Kenneth title = Alphavirus-Based Vaccines date = 2014-06-16 pages = extension = .txt mime = text/plain words = 6844 sentences = 322 flesch = 30 summary = Furthermore, sequential immunization with SIN and VEE replicon particles expressing the type 1 HIV gp140 envelope (Env) and trimeric Env protein in MF59 adjuvant provided partial protection in macaques against intravenous challenges with high doses of simian-human immunodeficiency virus (SHIV) [61] . In another study, chimeric VEE/SIN replicon particles were applied for the expression of measles virus hemagglutinin (H) and fusion (F) proteins, which elicited high-titer neutralizing antibody and IFNɤ-producing T-cells in macaques after intradermal vaccination [48] . Furthermore, vaccination with recombinant particles expressing the P1A gene [105] and the human papilloma virus (HPV) E7 gene [89] from SFV and VEE vectors, respectively, provided protection against further tumor development in mice. When TRAMP mice were prophylactically immunized with a prostate stem cell antigen (PSCA) DNA plasmid followed by VEE-PSCA particle administration, a specific immune response and anti-tumor protection were observed in 90% of vaccinated animals [102] . cache = ./cache/cord-313161-07iwwsfz.txt txt = ./txt/cord-313161-07iwwsfz.txt === reduce.pl bib === id = cord-313439-cadyykks author = Felten, Sandra title = Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature date = 2019-11-15 pages = extension = .txt mime = text/plain words = 12466 sentences = 522 flesch = 44 summary = Studies evaluating sensitivity and specificity of the detection of serum antibodies in comparison to either histopathology, a combination of diagnostic tests or clinical suspicion of feline infectious peritonitis (FIP). Recent studies evaluated the use of a quantitative RT-PCR (RT-qPCR) to detect FCoV RNA in FNA samples of the mesenteric lymph nodes and other abnormal tissues of clinical cases [119, 140] and hypothesized that this technique would be a useful tool to diagnose FIP for veterinary practitioners, especially in cats without effusion. Sensitivity and specificity from different studies evaluating the detection of feline coronavirus (FCoV) spike (S) gene mutations in tissue samples. RT-nPCR and subsequent S gene sequencing of serum and plasma samples from cats with FIP (diagnosed by histopathology ± IHC or by positive immunofluorescence in effusion) and control cats (diagnosed with another disease either ante or post mortem) revealed a sensitivity of only 7%, which confirms the very low virus load in blood. cache = ./cache/cord-313439-cadyykks.txt txt = ./txt/cord-313439-cadyykks.txt === reduce.pl bib === id = cord-314340-ltx4w9zh author = Zhu, Liqian title = The Involvement of Histone H3 Acetylation in Bovine Herpesvirus 1 Replication in MDBK Cells date = 2018-09-27 pages = extension = .txt mime = text/plain words = 6002 sentences = 282 flesch = 44 summary = During bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures, partial of intranuclear viral DNA is present in nucleosomes, and viral protein VP22 associates with histones and decreases histone H4 acetylation, indicating the involvement of histone H4 acetylation in virus replication. In this study, we demonstrated that BoHV-1 infection at the late stage (at 24 h after infection) dramatically decreased histone H3 acetylation [at residues K9 (H3K9ac) and K18 (H3K18ac)], which was supported by the pronounced depletion of histone acetyltransferases (HATs) including CBP/P300 (CREB binding protein and p300), GCN5L2 (general control of amino acid synthesis yeast homolog like 2) and PCAF (P300/CBP-associated factor). Indeed, 5 µM of AA treatment could inhibit histone H3 acetylation as demonstrated by the reduced levels of H3K9ac relative to the control, but AA increased the levels of H3K9ac in the context of virus infection in comparison to the mock treated but infected cells ( Figure 3E ,F). cache = ./cache/cord-314340-ltx4w9zh.txt txt = ./txt/cord-314340-ltx4w9zh.txt === 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-317026-9zgc6xrb author = Zhao, Shan title = Development and Validation of a S1 Protein-Based ELISA for the Specific Detection of Antibodies against Equine Coronavirus date = 2019-11-30 pages = extension = .txt mime = text/plain words = 6223 sentences = 317 flesch = 55 summary = In this study, an indirect enzyme-linked immunosorbent assay (ELISA) method utilizing ECoV spike S1 protein was developed in two formats, and further validated by analyzing 27 paired serum samples (acute and convalescent sera) from horses involved in an ECoV outbreak and 1084 sera of horses with unknown ECoV exposure. On the other hand, serological assays can be used to support the diagnosis of a clinical ECoV infection by showing seroconversion or a significant increase in antibody titer in paired serum samples. For the six horses that did not show a significant rise in VNT, five serum samples collected at the acute stage already had high antibody levels as shown by ELISA and neutralization assay (mean OD value > 2.6, mean VNT > 9, Table S1 ). For the six horses that did not show a significant rise in VNT, five serum samples collected at the acute stage already had high antibody levels as shown by ELISA and neutralization assay (mean OD value > 2.6, mean VNT > 9, Table S1 ). cache = ./cache/cord-317026-9zgc6xrb.txt txt = ./txt/cord-317026-9zgc6xrb.txt === reduce.pl bib === id = cord-314891-brgtwxhe author = Fumian, Tulio M. title = Potential Therapeutic Agents for Feline Calicivirus Infection date = 2018-08-16 pages = extension = .txt mime = text/plain words = 5483 sentences = 278 flesch = 47 summary = Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2′-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC(50) values in the low micromolar range (0.6 μM and 2.5 μM, respectively). The combined inhibitory effects of nitazoxanide (0 to 0.6 µM) and 2CMC (0 to 4 µM) were tested over a range of combinations against FCV in the cell culture using the plaque reduction assay. Of the six NNI compounds tested in the current study, PPNDS and quercetagetin showed an inhibition of FCV RdRp activity with IC 50 values in the low micromolar range (Figure 2 and Table 1 ). Finally, we reported the identification of two compounds (nitazoxanide and 2CMC) with antiviral activity against FCV in cell culture at low micromolar concentrations with a potential combinational therapeutic utility to treat FCV-infected cats. cache = ./cache/cord-314891-brgtwxhe.txt txt = ./txt/cord-314891-brgtwxhe.txt === reduce.pl bib === id = cord-315164-nidgnvvi author = Medkour, Hacène title = Adenovirus Infections in African Humans and Wild Non-Human Primates: Great Diversity and Cross-Species Transmission date = 2020-06-18 pages = extension = .txt mime = text/plain words = 6818 sentences = 359 flesch = 58 summary = Non-human primates (NHPs) are known hosts for adenoviruses (AdVs), so there is the possibility of the zoonotic or cross-species transmission of AdVs. As with humans, AdV infections in animals can cause diseases that range from asymptomatic to fatal. The aim of this study was to investigate the occurrence and diversity of AdVs in: (i) fecal samples of apes and monkeys from different African countries (Republic of Congo, Senegal, Djibouti and Algeria), (ii) stool of humans living near gorillas in the Republic of Congo, in order to explore the potential zoonotic risks. Samples were screened by real-time and standard PCRs, followed by the sequencing of the partial DNA polymerase gene in order to identify the AdV species. In the present study, we sought to investigate the presence and molecular diversity of AdVs in wild African NHPs, including great apes (gorillas and chimpanzees), macaques and other monkeys (baboons, green monkeys), living in close proximity to or outside human settlements. cache = ./cache/cord-315164-nidgnvvi.txt txt = ./txt/cord-315164-nidgnvvi.txt === reduce.pl bib === id = cord-317496-6o2upns3 author = Pascual-Iglesias, Alejandro title = Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV)—Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV date = 2019-07-25 pages = extension = .txt mime = text/plain words = 7100 sentences = 404 flesch = 48 summary = In this line, we engineered an attenuated virus based on the transmissible gastroenteritis virus (TGEV) genome, expressing a chimeric spike protein from a virulent United States (US) PEDV strain. The rTGEV-RS-SPEDV vaccine candidate was also attenuated in three-week-old animals that were used to evaluate the protection conferred by this virus, compared with the protection induced by infection with a virulent PEDV US strain (PEDV-NVSL). Interestingly, Viruses 2019, 11, 682 9 of 18 when viral RNA was isolated from feces of 21-day-old piglets at seven days post-vaccination (see below) and rTGEV-RS-SPEDV virus was sequenced, the same modifications were observed. An attenuated chimeric rTGEV virus expressing the ectodomain of a virulent US PEDV S protein (rTGEV-RS-SPEDV) was engineered as vaccine candidate for PEDV and evaluated in a young piglet model system. An attenuated chimeric rTGEV virus expressing the ectodomain of a virulent US PEDV S protein (rTGEV-RS-SPEDV) was engineered as vaccine candidate for PEDV and evaluated in a young piglet model system. cache = ./cache/cord-317496-6o2upns3.txt txt = ./txt/cord-317496-6o2upns3.txt === reduce.pl bib === id = cord-317587-rrx2r4n2 author = Fan, Wensheng title = Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure date = 2019-09-26 pages = extension = .txt mime = text/plain words = 9210 sentences = 479 flesch = 58 summary = title: Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure In conclusion, the IBVs circulating in southern China over the past decade have experienced a remarkable change in genetic diversity, dominant genotypes, and selection pressure, indicating the importance of permanent monitoring of circulating strains and the urgency for developing new vaccines to counteract the emerging LX4-type and New-type IBVs. Infectious bronchitis (IB) is one of the major viral diseases affecting the poultry industry globally. Our results indicated that there was a remarkable change in genetic diversity, dominant genotypes, and selection pressure of IBV strains in southern China over the past decade compared with the previous period of 1985-2007. Molecular characterization of major structural protein genes of avian coronavirus infectious bronchitis virus isolates in southern China cache = ./cache/cord-317587-rrx2r4n2.txt txt = ./txt/cord-317587-rrx2r4n2.txt === reduce.pl bib === id = cord-320212-fw51w4nm author = Friedman, Stephanie D. title = Genomic Sequences of two Novel Levivirus Single-Stranded RNA Coliphages (Family Leviviridae): Evidence for Recombinationin Environmental Strains date = 2012-09-13 pages = extension = .txt mime = text/plain words = 5349 sentences = 296 flesch = 51 summary = When the novel strains were compared to nine Levivirus genogroup I strains, they shared 95–100% similarity among the maturation, capsid and lysis proteins, but only 84–85% in the RNA-dependent RNA polymerase gene. In all analysis programs, the nucleotide or amino acid sequences were aligned to other strains and were therefore approximate positions on the replicase gene. Breakpoint nucleotides for strains DL52 and DL54 (when aligned to genogroup I strains) occurred between nt 84-592 and 84-401, respectively ( Figure 5 a, b) , corresponding to the approximate amino acid breakpoint positions of 133-197 within the replicase gene. Human Noroviruses, a positive sense ssRNA virus with a genome length of 7400-8300 nt, are considered to belong to a prototype strain if they share approximately 85% overall nucleotide sequence identity and a high amino acid sequence identity (>95%) in the polymerase gene [20] . cache = ./cache/cord-320212-fw51w4nm.txt txt = ./txt/cord-320212-fw51w4nm.txt === reduce.pl bib === id = cord-317715-xtsi663k author = Ortiz-Riaño, Emilio title = D471G Mutation in LCMV-NP Affects its Ability to Self-associate and Results in a Dominant Negative Effect in Viral RNA Synthesis date = 2012-10-16 pages = extension = .txt mime = text/plain words = 9164 sentences = 483 flesch = 52 summary = Reporter gene activation (FFL) is shown as percentage (%) of LCMV NP-NP wt interaction (pC-NP-VP16 and pC-NP-GAL4) after normalization of transfection efficiencies with the Renilla luciferase expression plasmid pRL SV40 (ii). Unexpectedly, the D471A substitution impeded both NP-NP and NP-Z interactions, as well as NP functions in replication and transcription of the LCMV MG and the ability of NP to counteract SeV-mediated induction of the host IFN-I response, suggesting that change D to A at position 471 might have affected the overall structure of NP without affecting its stability as reflected by its unchanged expression levels determined by WB using anti-VP16 ( Figures 6A and 6B ) or anti-HA ( Figures 6C and 6D) antibodies. (C) Replication and transcription activity: BHK-21 cells were co-transfected with the LCMV MG as described in Figure 3 together with expression plasmids for the viral polymerase (L) and wt or indicated mutant NPs, and pSV40-Cluc expression vector to normalize transfection efficiencies. cache = ./cache/cord-317715-xtsi663k.txt txt = ./txt/cord-317715-xtsi663k.txt === reduce.pl bib === id = cord-317037-1qydcc5e author = Kumar, Asit title = Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention date = 2020-08-13 pages = extension = .txt mime = text/plain words = 9406 sentences = 511 flesch = 37 summary = Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from the plasma membrane. HIV-infected U1 macrophages upon Cigarette smoke condensate (CSC) treatment enhanced the packaging of IL-6 in EVs; IL-8 served as a biomarker for HIV patients with altered immune function due to alcohol and tobacco abuse [20, 116, 117] Host protein APOBEC3G Inhibit replication of viral infectivity factor (vif) -deficient and wild-type HIV-1 in recipient cells [118] miRNA vmiR-88 and vmiR-99 Hepatocytes secreted exosomes participate in virus replication [142] Viral miRNAs HBV-miR-3 Represses viral protein production and HBV replication [143] HTLV-1 Viral proteins gp61, Tax, and HBZ Increase cell-to-cell contact and promote a potential increase in viral spread [144] Zika Viral genetic material and protein RNA and ZIKV-E EVs derived from Infected C6/36 cells promote infection and activation of monocytes with enhanced TNF-α mRNA expression. cache = ./cache/cord-317037-1qydcc5e.txt txt = ./txt/cord-317037-1qydcc5e.txt === reduce.pl bib === id = cord-320015-lbr2q4qh author = Chinchar, V. Gregory title = The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date = 2011-10-20 pages = extension = .txt mime = text/plain words = 9130 sentences = 433 flesch = 43 summary = Additional IE and DE proteins include proteins that may play roles in blocking host immune responses such as a virus-encoded, CARD (caspase activation and recruitment domain) motif-containing protein (vCARD), β-hydroxysteroid dehydrogenase (βHSD), and a RNAse III-like protein, catalytic proteins involved in nucleic acid synthesis (Proliferating Cell Nuclear Antigen [PCNA], DNA methyltransferase [DMTase], the large and small subunits of the viral homolog of cellular RNA polymerase II [vPOL-IIα and -IIβ], transcription factor IIS), catalytic proteins that may act to increase dTTP pool sizes and influence host range (deoxyuridine triphosphatase [dUTPase], deoxynucleotide kinase, the large and small subunits of ribonucleotide reductase), and proteins non-essential for replication in vitro, but needed for growth in vivo (the 18K protein) [22] . Lastly, Sample and co-workers observed that KD of the 18K IE protein had no observable effect on viral gene expression or replication in vitro suggesting that, at least in fathead minnow cells, 18K was not required for the production of infectious virions. cache = ./cache/cord-320015-lbr2q4qh.txt txt = ./txt/cord-320015-lbr2q4qh.txt === reduce.pl bib === id = cord-320921-eumuid3r author = Widagdo, W. title = Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits date = 2019-04-24 pages = extension = .txt mime = text/plain words = 4829 sentences = 239 flesch = 51 summary = Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission. Besides dromedary camels, other animal species, i.e. llamas, alpacas, and pigs have been shown to be susceptible and develop upper respiratory tract infection upon experimental intranasal MERS-CoV inoculation [9] [10] [11] . We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ). We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ). cache = ./cache/cord-320921-eumuid3r.txt txt = ./txt/cord-320921-eumuid3r.txt === reduce.pl bib === id = cord-321080-pgxxkfc0 author = Wang, Cong title = Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD date = 2019-01-06 pages = extension = .txt mime = text/plain words = 4553 sentences = 191 flesch = 49 summary = We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. As shown in Figure 2 and Table 1 , combining HR2P-M2 and m336 resulted in strong synergistic inhibitory activity against MERS-CoV pseudovirus infection with CI values of 0.13-0.20 for 50-90% inhibition, including potency enhancement of 12.9-to 18.9-fold for m336 and 8.4-to 12.9-fold for HR2P-M2. cache = ./cache/cord-321080-pgxxkfc0.txt txt = ./txt/cord-321080-pgxxkfc0.txt === reduce.pl bib === id = cord-321013-8pkrg0mx author = McBride, Ruth title = The Coronavirus Nucleocapsid Is a Multifunctional Protein date = 2014-08-07 pages = extension = .txt mime = text/plain words = 10761 sentences = 476 flesch = 44 summary = The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. The M protein is the main core shell component and a 16 amino acid domain (aa 237-252) on the CTD of M protein binds directly to N protein via an ionic interaction, leading to specific genome encapsidation in the budding viral particle [81] [82] [83] .The N protein therefore plays an essential structural role in the CoV virion through a network of interactions with (i) the genomic RNA; (ii) M protein and (iii) other N proteins. Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA cache = ./cache/cord-321013-8pkrg0mx.txt txt = ./txt/cord-321013-8pkrg0mx.txt === reduce.pl bib === id = cord-321441-t1v0pu0w author = Yang, Yiming title = Polycistronic Genome Segment Evolution and Gain and Loss of FAST Protein Function during Fusogenic Orthoreovirus Speciation date = 2020-06-29 pages = extension = .txt mime = text/plain words = 8639 sentences = 363 flesch = 41 summary = New phylogenetic analyses that included the atypical waterfowl subgroup of avian reoviruses and recently identified new orthoreovirus species indicate a more complex relationship between reovirus speciation and fusogenic capacity, with numerous predicted internal indels and 5'-terminal extensions driving the evolution of the orthoreovirus' polycistronic genome segments and their encoded FAST and fiber proteins. We further show that two distinct post-speciation genetic events led to the loss of fusion in the waterfowl isolates of avian reovirus, a recombination event that replaced the p10 FAST protein with a heterologous, non-fusogenic protein and point substitutions in a conserved motif that destroyed the p10 assembly into multimeric fusion platforms. MdRVs are divided into two subgroups, the "classical" and "novel" MdRVs. Classical Muscovy duck reoviruses (MdRVc) possess a bicistronic S4 genome segment encoding a truncated fiber protein of 269 residues and a p11 protein that lacks sequence similarity to the p10 FAST proteins of ARV, ARVN, and NBV ( Figure 1B ) [50] . cache = ./cache/cord-321441-t1v0pu0w.txt txt = ./txt/cord-321441-t1v0pu0w.txt === reduce.pl bib === id = cord-322206-roxa3ix6 author = I. Sardi, Silvia title = High-Quality Resolution of the Outbreak-Related Zika Virus Genome and Discovery of New Viruses Using Ion Torrent-Based Metatranscriptomics date = 2020-07-21 pages = extension = .txt mime = text/plain words = 4199 sentences = 212 flesch = 46 summary = Herein, we used RNA-based metatranscriptomics associated with Ion Torrent deep sequencing to allow for the high-quality reconstitution of an outbreak-related Zika virus (ZIKV) genome (10,739 nt), with extended 5′-UTR and 3′-UTR regions, using a newly-implemented bioinformatics approach. Besides allowing for the assembly of one of the largest complete ZIKV genomes to date, our strategy also yielded high-quality complete genomes of two arthropod-infecting viruses co-infecting C6/36 cell lines, namely: Alphamesonivirus 1 strain Salvador (20,194 nt) and Aedes albopictus totivirus-like (4618 nt); the latter likely represents a new viral species. Altogether, our results demonstrate that our bioinformatics approach associated with Ion Torrent sequencing allows for the high-quality reconstruction of known and unknown viral genomes, overcoming the main limitation of RNA deep sequencing for virus identification. Here, we applied RNA-based metatranscriptomics associated with Ion Torrent deep sequencing and a newly developed Bioinformatics approach to the high-quality reconstitution of viral genomes. cache = ./cache/cord-322206-roxa3ix6.txt txt = ./txt/cord-322206-roxa3ix6.txt === reduce.pl bib === id = cord-321673-v5o49ees author = Nieto-Torres, Jose L. title = Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis date = 2015-07-03 pages = extension = .txt mime = text/plain words = 8398 sentences = 451 flesch = 38 summary = Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Noticeably, these proteins oligomerize in cell membranes to form ion conductive pores, which generally display mild ion selectivity, indicating that viroporins do not show preference for particular ionic species. Influenza viruses lacking M2 ion conductivity, presented either a 15-fold reduction of viral titer in tissue culture [74] , or showed a standard production in cell culture but a restricted growth in the nasal turbinates of infected mice [75] . Several compounds inhibit viroporin ion conductivity in artificial lipid membranes, and some of them efficiently reduce viral growth when administered to infected cells. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells cache = ./cache/cord-321673-v5o49ees.txt txt = ./txt/cord-321673-v5o49ees.txt === reduce.pl bib === id = cord-323569-ksodnkic author = Xu, Shengnan title = A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice date = 2019-12-11 pages = extension = .txt mime = text/plain words = 5550 sentences = 316 flesch = 56 summary = title: A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. Immunization of mice with ISA 201VG mixed with Poly (I:C)-adjuvanted SBLP resulted in significant increases in SUDV GP-specific IgG, IgG1, and IgG2a and SUDV pseudotyped virus-neutralizing antibody titers, which are considered to be important correlates of protection [34, 49] . Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice cache = ./cache/cord-323569-ksodnkic.txt txt = ./txt/cord-323569-ksodnkic.txt === reduce.pl bib === id = cord-323585-iv2dcpqj author = Li, Su title = eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus date = 2015-08-10 pages = extension = .txt mime = text/plain words = 6142 sentences = 343 flesch = 59 summary = The NS5A protein of classical swine fever virus (CSFV) is involved in the RNA synthesis and viral replication. The GST or GST-NS5A fusion proteins expressed in Escherichia coli BL21(DE3) were purified with glutathione Sepharose 4B resin and incubated with the lysate of HEK293T cells overexpressing the Myc-tagged eEF1A. The immunoprecipitate was analyzed by Western blotting using the anti-Flag MAb (1:1000) and a rabbit anti-Myc PAb (1:500); (D) Co-IP analysis of eEF1A and NS5A by the anti-Myc MAb. HEK293T cells were cotransfected with the indicated plasmids (+) or empty vectors ('), the cell lysate was collected at 48 h post-transfection (hpt), incubated with the anti-Myc MAb and Protein G-Agarose. The bound proteins were analyzed by immunoblotting using the anti-Myc monoclonal antibody (MAb) (1:1000); (B) eEF1A interacts with the CSFV IRES in a dose-dependent manner. The bound proteins were analyzed by immunoblotting using the anti-Myc monoclonal antibody (MAb) (1:1000); (B) eEF1A interacts with the CSFV IRES in a dose-dependent manner. cache = ./cache/cord-323585-iv2dcpqj.txt txt = ./txt/cord-323585-iv2dcpqj.txt === reduce.pl bib === id = cord-325574-4zf9qtlh author = Farag, Elmoubasher title = Drivers of MERS-CoV Emergence in Qatar date = 2018-12-31 pages = extension = .txt mime = text/plain words = 4343 sentences = 236 flesch = 59 summary = MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. The transition in husbandry leading to high density camel farming along with increased exposure to humans, combined with the increase of camel movement for the racing and breeding industry, have led to a convergence of factors driving spillover of MERS-CoV from camels to humans. By reviewing changes involving humans and camels over the past 30 years in Qatar, this study sought to identify the key drivers of the emergence and spread of MERS-CoV. The main themes that were covered during the interviews included: (changes in) people's living conditions; customs and purposes of camel ownership; cultural habits related to camels; educational level and personal behaviors of camel owners and workers; camel movement; demographic distribution of camels in Qatar; camel farming practices: feeding, grazing, and slaughter. cache = ./cache/cord-325574-4zf9qtlh.txt txt = ./txt/cord-325574-4zf9qtlh.txt === reduce.pl bib === id = cord-324617-yok7mh70 author = Andreata-Santos, Robert title = Transcutaneous Administration of Dengue Vaccines date = 2020-05-06 pages = extension = .txt mime = text/plain words = 6337 sentences = 283 flesch = 44 summary = Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. The addition of LT1 to the vaccines significantly enhanced the DENV2-specific serum IgG responses elicited in the mice immunized via the TC or ID route, with the maximal values reached two weeks after the third vaccine dose ( Figure 1A ,B). The ID-immunized mice showed significant differences in DENV2-specific serum IgG responses in the presence of LT1, particularly in the group immunized with 50 µg of the tested antigen ( Figure 1D ). The ID-immunized mice showed significant differences in DENV2-specific serum IgG responses in the presence of LT1, particularly in the group immunized with 50 µg of the tested antigen ( Figure 1D ). cache = ./cache/cord-324617-yok7mh70.txt txt = ./txt/cord-324617-yok7mh70.txt === reduce.pl bib === id = cord-323995-cpn34j02 author = Chen, Jun title = Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response date = 2017-12-01 pages = extension = .txt mime = text/plain words = 8131 sentences = 407 flesch = 51 summary = To test this hypothesis, we analyzed the kinetics of CypA RNA expression by quantitative real-time PCR, intracellular CypA (inCypA), and secreted CypA (sCypA) protein levels by Western blot analysis following HCMV infection of HFF cells. To test this hypothesis, we analyzed the kinetics of CypA RNA expression by quantitative real-time PCR, intracellular CypA (inCypA), and secreted CypA (sCypA) protein levels by Western blot analysis following HCMV infection of HFF cells. Moreover, we found that endogenous CD147 was targeted by HCMV-encoded miR-US25-1-5p at the 3 UTR, which could replace CD147-specific siRNA mimics in inhibiting the CD147-mediated early innate immune response to HCMV infection ( Figure 4) . Moreover, we found that endogenous CD147 was targeted by HCMV-encoded miR-US25-1-5p at the 3 UTR, which could replace CD147-specific siRNA mimics in inhibiting the CD147-mediated early innate immune response to HCMV infection ( Figure 4) . cache = ./cache/cord-323995-cpn34j02.txt txt = ./txt/cord-323995-cpn34j02.txt === reduce.pl bib === id = cord-325823-bt7xo9iq author = Magassouba, N’Faly title = A Sporadic and Lethal Lassa Fever Case in Forest Guinea, 2019 date = 2020-09-23 pages = extension = .txt mime = text/plain words = 3342 sentences = 190 flesch = 62 summary = In January 2019, a 35-year-old man, a wood merchant from Kissidougou, Forest Guinea, presented himself at several health centers with persistent fever, frequent vomiting and joint pain. Due to the similarity of symptoms with malaria, Lassa fever is still a disease that is difficult to recognize and that may remain undiagnosed in health centers in Guinea. However, Guinea has very few reported acute human cases, and only a few studies have a posteriori described acute Lassa fever cases in the prefectures of Kindia, Faranah, Kissidougou, Guekedou, Macenta and N'Zérékoré in 1992 and 1996-1999 [12] [13] [14] . A total of 41 individuals in contact with the case in Kissidougou (n = 7), Mamou (n = 32) and Conakry (n = 2) were identified by the field teams, and further sampled for LASV RT-PCR as per Ministry of Health National Strategy guidelines in the case of VHF suspicion even in the absence of symptoms. cache = ./cache/cord-325823-bt7xo9iq.txt txt = ./txt/cord-325823-bt7xo9iq.txt === reduce.pl bib === id = cord-326319-3538jmqd author = Yuan, Yuan title = Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins date = 2018-06-27 pages = extension = .txt mime = text/plain words = 7470 sentences = 370 flesch = 54 summary = title: Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). At 14 dpv, IBV-specific antibody levels in birds immunized with subunit vaccines rHBM-S1-N, rHBM-S1, rHBM-N and inactivated vaccine strain H120 started to rise (p > 0.05). At 14 dpv, IBV-specific antibody levels in birds immunized with subunit vaccines rHBM-S1-N, rHBM-S1, rHBM-N and inactivated vaccine strain H120 started to rise (p > 0.05). Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus The S1 glycoprotein but not the N or M proteins of avian infectious bronchitis virus induces protection in vaccinated chickens cache = ./cache/cord-326319-3538jmqd.txt txt = ./txt/cord-326319-3538jmqd.txt === reduce.pl bib === id = cord-328042-e1is656g author = Klein, Steffen title = SARS-CoV-2 RNA Extraction Using Magnetic Beads for Rapid Large-Scale Testing by RT-qPCR and RT-LAMP date = 2020-08-07 pages = extension = .txt mime = text/plain words = 6328 sentences = 329 flesch = 56 summary = The standard diagnostic pipeline for testing SARS-CoV-2 presence in patients with an ongoing infection is predominantly based on pharyngeal swabs, from which the viral RNA is extracted using commercial kits, followed by reverse transcription and quantitative PCR detection. Comparable viral RNA detection sensitivity and specificity were obtained by fluorescent and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) using a primer set targeting the N gene, as well as RT-qPCR using a primer set targeting the E gene, showing that the RNA extraction protocol presented here can be combined with a variety of detection methods at high throughput. Here, we show that the magnetic bead-based protocol yields RNA extracts comparable to the commercially available QIAcube viral RNA extraction kit, as determined by the commonly applied detection methods RT-qPCR and reverse transcription loop-mediated isothermal amplification (RT-LAMP) [16] . cache = ./cache/cord-328042-e1is656g.txt txt = ./txt/cord-328042-e1is656g.txt === reduce.pl bib === id = cord-326614-cik3ino6 author = Corder, Brigette N. title = A Decade in Review: A Systematic Review of Universal Influenza Vaccines in Clinical Trials during the 2010 Decade date = 2020-10-20 pages = extension = .txt mime = text/plain words = 7511 sentences = 488 flesch = 46 summary = These trials include a variety of viral targets, vaccine platforms, and adjuvants to boost the immune response to vaccination. Another vaccine utilized the full-length H5 HA protein in an oral recombinant adenovirus type 4 (Ad4) vectored vaccine, Ad4-H5-Vtn. Three clinical trials have enrolled 313 participants between 18 and 49 years of age to investigate this avian H5 influenza vaccine. Although results for the phase II trial have not been posted, a press release from Novavax stated that NanoFlu induced superior HAI antibody responses against homologous and drifted strains compared to the seasonal influenza vaccine. Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: Study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: A phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults cache = ./cache/cord-326614-cik3ino6.txt txt = ./txt/cord-326614-cik3ino6.txt === reduce.pl bib === id = cord-330767-jja2wcfz author = Voigt, Kathleen title = Fusogenicity of the Ghana Virus (Henipavirus: Ghanaian bat henipavirus) Fusion Protein is Controlled by the Cytoplasmic Domain of the Attachment Glycoprotein date = 2019-08-29 pages = extension = .txt mime = text/plain words = 6059 sentences = 263 flesch = 48 summary = Here, we generated truncated as well as chimeric GhV G proteins and investigated the influence of the structural domains (cytoplasmic tail, transmembrane domain, ectodomain) of this protein on the intracellular transport and the fusogenicity following coexpression with the GhV fusion protein (F). In previous studies, it has been shown that the transport of GhV G to the cell surface is significantly reduced compared to NiV G and that the majority of the GhV G protein accumulates in the endoplasmic reticulum (ER), suggesting that the amount of surface-expressed GhV G is not efficient enough to trigger conformational changes in the F protein that are required to acquire the fusion-active form of F [35, 36] . However, whereas the glycoproteins of NiV and HeV induce cell-to-cell fusion in a broad variety of cells from different host species, syncytium formation upon expression of GhV F and G proteins is restricted to certain bat cells [32] [33] [34] [35] . cache = ./cache/cord-330767-jja2wcfz.txt txt = ./txt/cord-330767-jja2wcfz.txt === reduce.pl bib === id = cord-328259-3g4klpyg author = Guajardo-Leiva, Sergio title = Metagenomic Insights into the Sewage RNA Virosphere of a Large City date = 2020-09-21 pages = extension = .txt mime = text/plain words = 7626 sentences = 370 flesch = 47 summary = Despite the overrepresentation of dsRNA viruses, our results show that Santiago's sewage RNA virosphere was composed mostly of unknown sequences (88%), while known viral sequences were dominated by viruses that infect bacteria (60%), invertebrates (37%) and humans (2.4%). Viral sequences identified as Partitiviridae-like viruses included in the "unclassified RNA viruses ShiM-2016" category in the NCBI taxonomy (~25% abundance; Figure 2B ) and Totiviriade family were also highly abundant in treated and untreated sewage samples from the EU [5, 7] . Therefore, the abundance of these viruses in the Trebal metagenome can expand the known sequence space associated with this family (only 10 genomes are currently available in the NCBI database) and contribute to a better understanding of the bacteriophage biology related to RNA genomes. Taken together, our results show that metagenomic surveys of RNA viruses in sewage samples and the use of HMMs could uncover extraordinary viral diversity through the detection of remote homologs in these human-impacted environments. cache = ./cache/cord-328259-3g4klpyg.txt txt = ./txt/cord-328259-3g4klpyg.txt === reduce.pl bib === id = cord-330475-mameyzih author = Shi, Da title = Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus date = 2014-03-13 pages = extension = .txt mime = text/plain words = 5570 sentences = 296 flesch = 44 summary = Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. The B23.1-DsRed fusion protein was used to tag the nucleolus, so we could analyze nucleolar localization properties and colocalization in cotransfected cells by live cell imaging (direct fluorescence) or confocal microscopy. These expression plasmids were transfected into Vero E6 cells, the nuclear was stained with DAPI at 24 h post-transfection indicated that amino acids 148-220 directed AcGFP to the cytoplasm and nucleus and had a subcellular localization similar to AcGFP. cache = ./cache/cord-330475-mameyzih.txt txt = ./txt/cord-330475-mameyzih.txt === reduce.pl bib === id = cord-331094-22366b81 author = Ianevski, Aleksandr title = Potential Antiviral Options against SARS-CoV-2 Infection date = 2020-06-13 pages = extension = .txt mime = text/plain words = 6822 sentences = 424 flesch = 49 summary = We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. After the initial screening, we identified apilimod, emetine, amodiaquine, obatoclax, homoharringtonine, salinomycin, arbidol, posaconazole and nelfinavir as compounds that rescued virus-infected cells from death (AUC from 285 to 585; Table S1 ). We next profiled transcriptional responses to nelfinavir, amodiaquine or both drugs in virus-or mock-infected Vero-E6 cells at 24 h. Anti-SARS-CoV-2 activity of safe-in man broad-spectrum antivirals in Vero-E6 cells. Here, we found that combinations of nelfinavir with salinomycin, amodiaquine, obatoclax, emetine or homoharringtonine were synergistic against SARS-CoV-2 in Vero-E6 cells. Thus, the amodiaquine and nelfinavir combination could result in better efficacy and decreased toxicity for the treatment of SARS-CoV-2 and perhaps other viral infections. Transcriptomic analysis of mock-and SARS-CoV-2-infected Vero-E6 cells treated with nelfinavir, amodiaquine or both drugs. cache = ./cache/cord-331094-22366b81.txt txt = ./txt/cord-331094-22366b81.txt === reduce.pl bib === id = cord-332576-pd62s65y author = Lu, Chien-Yi title = Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus date = 2017-04-10 pages = extension = .txt mime = text/plain words = 7343 sentences = 352 flesch = 46 summary = This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins. The expression of EGFP and viral proteins as well as the synthesis of positive-and negative-sense RNA subgenomes in MJ-47-reated infected cells were determined using fluorescent microscope, immunofluorescent staining and real-time RT-PCR assays, as described above. Real-time RT-PCR and immunofluorescent staining demonstrated JEV-EGFP replicon-driven viral positive-and negative-sense RNA genomes were synthesized, as well as replicon-driven EGFP and viral non-structural proteins being expressed in the packaging cell line (Figures 3 and 4) . Real-time RT-PCR and immunofluorescent staining demonstrated JEV-EGFP replicon-driven viral positive-and negative-sense RNA genomes were synthesized, as well as replicon-driven EGFP and viral non-structural proteins being expressed in the packaging cell line (Figures 3 and 4) . cache = ./cache/cord-332576-pd62s65y.txt txt = ./txt/cord-332576-pd62s65y.txt === reduce.pl bib === id = cord-331414-i0oxm5mr author = Kautz, Tiffany F. title = A Low Fidelity Virus Shows Increased Recombination during the Removal of an Alphavirus Reporter Gene date = 2020-06-19 pages = extension = .txt mime = text/plain words = 5064 sentences = 241 flesch = 45 summary = To examine this, GFP was inserted into TC-83, a live-attenuated vaccine for the alphavirus Venezuelan equine encephalitis virus, as well as a low-fidelity variant of TC-83, and passaged until fluorescence was no longer observed. To examine reporter gene stability, three independent replicates of TC-83 GFP and low-fidelity TC-83 GFP were passaged 10 times on Vero cells using an approximate MOI of 0.5 ( Figure 1A ). All three TC-83 GFP replicates contained deletion variants present at a low frequency that were able to selectively remove the GFP reporter gene by passage 10 (Figure 2A) . To better understand the mechanisms underlying the conserved removal of the low-fidelity TC-83 GFP gene, M-fold was used to determine the RNA secondary structure of the virus genome ( Figure 4C-E) . To characterize the role of RNA structure of the virus genome in RNA recombination site selection, we modeled the three most common deletions that occurred at high levels during low-fidelity TC-83 GFP passaging. cache = ./cache/cord-331414-i0oxm5mr.txt txt = ./txt/cord-331414-i0oxm5mr.txt === reduce.pl bib === id = cord-332915-4o2dsf56 author = Hong, Seung-Min title = Pathobiological and Genomic Characterization of a Cold-Adapted Infectious Bronchitis Virus (BP-caKII) date = 2018-11-19 pages = extension = .txt mime = text/plain words = 5904 sentences = 310 flesch = 56 summary = We established a cold-adapted infectious bronchitis virus (BP-caKII) by passaging a field virus through specific pathogen-free embryonated eggs 20 times at 32 °C. In this study, we established a cold-adapted IBV (BP-caKII), and we characterized its pathogenicity in embryos and chickens, tissue tropism, and persistence of infection. We applied a premature reproductive tract pathogenicity model to the differentiation of the pathogenicity of IBVs and performed comparative genomics to shed light on the genetic background of the embryo adaptation of K2 and the cold adaptation of BP-caKII. To test virus titer and embryo pathogenicity, BP-caKII was inoculated into 10-day-old SPF embryonated eggs (Valo Biomedia) via the allantoic cavity route and incubated at 37 • C for 48 h. SNU9106 was passaged 20 times through three embryonated eggs by inoculating allantoic fluid with high virus titer, and BP-caKII was established. SNU9106 was passaged 20 times through three embryonated eggs by inoculating allantoic fluid with high virus titer, and BP-caKII was established. cache = ./cache/cord-332915-4o2dsf56.txt txt = ./txt/cord-332915-4o2dsf56.txt === reduce.pl bib === id = cord-332165-31tbc31x author = Rustmeier, Nils H. title = The Symmetry of Viral Sialic Acid Binding Sites—Implications for Antiviral Strategies date = 2019-10-14 pages = extension = .txt mime = text/plain words = 5820 sentences = 316 flesch = 43 summary = In this review, we will evaluate the structures of non-enveloped virus capsid proteins bound to sialylated glycan receptors and discuss the potential of these structures for the development of potent antiviral attachment inhibitors. This concept of targeting multiple, symmetric receptor binding sites by multivalent inhibitors is also applicable for many viruses, since viral capsids are often icosahedral and, therefore, highly symmetric structures. Many members of the polyomavirus family bind sialic acid-based glycans using their VP1 proteins, so the binding sites on individual pentamers are always linked by local five-fold symmetry (Figure 4a , TSPyV). The glycooligopeptide-VP1 complex structures displayed a similar ligand binding mode that was reported for sialic acid in an earlier study [50] and showed, for the compounds, that the linker between the ligand and the scaffold occupies the space that is usually targeted by the natural glycan receptor moieties (Figure 5a,b, right) . cache = ./cache/cord-332165-31tbc31x.txt txt = ./txt/cord-332165-31tbc31x.txt === reduce.pl bib === id = cord-334027-xhfmio7k author = Fagre, Anna C. title = Can Bats Serve as Reservoirs for Arboviruses? date = 2019-03-03 pages = extension = .txt mime = text/plain words = 8738 sentences = 492 flesch = 43 summary = No demonstrable pathologic effects noted during infection of three bat species [big brown bats (Eptesicus fuscus), little brown bats (Myotis lucifigus) and Mexican free-tailed bats (Tadarida brasiliensie mexicana) with various strains of JBEV or St. Louis encephalitis virus (SLEV) [69] . While experimental data demonstrated that some bat species can sustain JBEV infections and support mosquito-borne transmission of this virus, the epidemiological significance of these observations in the field remains unclear. To truly elucidate the role of bats as reservoirs for arboviruses, field surveillance studies documenting natural infection and transmission dynamics among vector and vertebrate species must be supplemented with experimental infections to characterize viremia profiles and infectiousness to vectors, virus-induced pathology, and immune kinetics following infection. The isolation of Marburg virus from Egyptian rousette bats in Uganda in addition to experimental infections demonstrating viremia and shedding in the absence of overt pathology support the role of this bat species as the reservoir for Marburg virus [6, 7, 208] . cache = ./cache/cord-334027-xhfmio7k.txt txt = ./txt/cord-334027-xhfmio7k.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-334560-1j9zmuub author = Hunt, Catherine L. title = Filovirus Entry: A Novelty in the Viral Fusion World date = 2012-02-07 pages = extension = .txt mime = text/plain words = 6445 sentences = 301 flesch = 48 summary = Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. However, for reasons that are not entirely clear, this type of study has not been successful in identifying cell surface proteins that directly interact with EBOV GP to mediate virus entry [41, 42] . However, as both of these regions can be deleted from EBOV GP 1 without loss of viral transduction efficiency [16, [50] [51] [52] , it is likely that C-type lectins increase filovirus attachment to cells rather than serving as cellular receptors that mediate internalization of the virus into endosomes [53] . cache = ./cache/cord-334560-1j9zmuub.txt txt = ./txt/cord-334560-1j9zmuub.txt === reduce.pl bib === id = cord-334855-s0ci3r8w author = Andersen, Petter I. title = Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine date = 2019-10-18 pages = extension = .txt mime = text/plain words = 4274 sentences = 272 flesch = 48 summary = Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. The expected response of the emetine-obatoclax drug combination on the viability of FLUAV-and mock-infected RPE cells was calculated using Bliss reference model [29] . After the initial screening, we identified four compounds (obatoclax, emetine, niclosamide and ganciclovir) that at none-cytotoxic concentrations rescued cells from virus-mediated death (Figure 2A) . Table S1 : Compounds, their suppliers and catalogue numbers; Table S2 : Developmental status of broad-spectrum antivirals used in the study; Table S3 : Human viruses and associated diseases; Figure S1 : The expected response of the emetine-obatoclax drug combination on the viability of FLUAV-and mock-infected RPE cells, as measured with the CTG assay using the Bliss reference model; Figure S2 cache = ./cache/cord-334855-s0ci3r8w.txt txt = ./txt/cord-334855-s0ci3r8w.txt === reduce.pl bib === id = cord-335279-cfv18qn0 author = Paillot, Romain title = Special Issue “Equine Viruses”: Old “Friends” and New Foes? date = 2020-01-29 pages = extension = .txt mime = text/plain words = 2070 sentences = 112 flesch = 49 summary = With this Special Issue, which assembles a collection of communications, research articles, and reviews, we intend to explore our understanding of a panel of equine viruses, looking at their pathogenicity, their importance in terms of welfare and potential association with diseases, their economic importance and impact on performance, and how their identification can be helped by new technologies and methods. The authors highlight the potential protective role of eqMx1, which primarily targets the virus nucleoprotein (NP), against the transmission of new IAVs in horses (i.e., eqMx1 could only inhibit the polymerase activity of IAVs of avian and human origin but remained inactive against the equine IAVs tested). To date, equine influenza virus remains one of the most important respiratory pathogens of horses worldwide, with a potential damaging impact on the equine industry, as clearly illustrated in 2007 in Australia and in 2019 in Europe [20, 21] . cache = ./cache/cord-335279-cfv18qn0.txt txt = ./txt/cord-335279-cfv18qn0.txt === reduce.pl bib === id = cord-335567-ssnvr6nj author = Berry, Michael title = Identification of New Respiratory Viruses in the New Millennium date = 2015-03-06 pages = extension = .txt mime = text/plain words = 7477 sentences = 379 flesch = 40 summary = In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. In recent years six new human respiratory viruses have been reported including human metapneumovirus (hMPV) [16] , bocavirus and four new human coronaviruses including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), HCoV-HKU1 and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children Genetic variability of human coronavirus OC43-, 229E-, and NL63-like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients cache = ./cache/cord-335567-ssnvr6nj.txt txt = ./txt/cord-335567-ssnvr6nj.txt === reduce.pl bib === id = cord-335614-qh98622y author = Xu, Puzhi title = A Multi-Omics Study of Chicken Infected by Nephropathogenic Infectious Bronchitis Virus date = 2019-11-16 pages = extension = .txt mime = text/plain words = 6543 sentences = 352 flesch = 41 summary = These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout. The results of PCA and OPLA-DA analysis showed that there was an obvious separation between the content of the Con and Dis groups, revealing significant changes in the concentrations of metabolites in the kidney induced by NIBV infection. In addition, the transcriptomic analysis showed that NIBV infection also activated the RIG-I-like receptor signalling pathway (Figure 3f , signal 2), which included the transcriptional upregulation of genes such as MDA5, IPS-1, TRAF3, and IκB. In the present study, the ABCG2 mRNA was downregulated in the model group chicken kidneys, partially explaining the significantly increased uric acid levels caused by NIBV infection. cache = ./cache/cord-335614-qh98622y.txt txt = ./txt/cord-335614-qh98622y.txt === reduce.pl bib === id = cord-337339-0vkigjv2 author = Osterrieder, Nikolaus title = Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters date = 2020-07-20 pages = extension = .txt mime = text/plain words = 4327 sentences = 220 flesch = 47 summary = We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information, as this small-animal model appears to mirror age-dependent differences in human patients. Moreover, transgenic mice expressing human ACE2 represent a lethal SARS-CoV-2 infection model resulting in significant weight loss and permitting robust virus replication in the respiratory tract including the lungs [20] . In contrast to SARS-CoV-2 titers, histopathological changes differed markedly between young and aged Syrian hamsters over time: younger animals launched more severe reactions at early time points after infection, while lesions and inflammation in the lungs became more pronounced and widespread at later time points in the elderly. Based on the data presented here, we propose that comparative preclinical assessments of SARS-CoV-2 vaccines and other treatment options in young versus aged hamsters may yield valuable and relevant results, as this small animal model appears to mimic age-dependent differences in humans. cache = ./cache/cord-337339-0vkigjv2.txt txt = ./txt/cord-337339-0vkigjv2.txt === reduce.pl bib === id = cord-336536-ie5ok0lz author = Yeh, Ming Te title = Mapping Attenuation Determinants in Enterovirus-D68 date = 2020-08-08 pages = extension = .txt mime = text/plain words = 8258 sentences = 401 flesch = 56 summary = A single amino acid change from isoleucine to valine at position 88 in VP3 attenuated neurovirulence by reducing virus replication in the brain and spinal cord of infected mice. To identify the potential virulence determinant, sequences of NR-49129, NR-49130, NR-49131 and CA/14-4231 were aligned to reveal conserved genetic changes that we defined as nucleotides in 5 -UTR and amino acids in the coding region that are present only in the non-pathogenic strain but not in pathogenic ones (Supplementary Data S1 and S2). While mutation VP1-L1P allowed a 50% survival of infected mice, VP3-I88V did not cause disease, suggesting its role as major virulence determinant for EV-D68 in this mouse model ( Figure 5E ). While mutation VP1-L1P allowed a 50% survival of infected mice, VP3-I88V did not cause disease, suggesting its role as major virulence determinant for EV-D68 in this mouse model ( Figure 5E ). cache = ./cache/cord-336536-ie5ok0lz.txt txt = ./txt/cord-336536-ie5ok0lz.txt === reduce.pl bib === id = cord-337707-xbwilp1w author = Kin, Nathalie title = Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes date = 2015-05-07 pages = extension = .txt mime = text/plain words = 5401 sentences = 275 flesch = 56 summary = title: Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. Based on a bootscan analysis of the complete genome of the 3 HCoV-OC43s belonging to the circulating genotypes B, C, and D, it was assumed that a hot spot was likely located between the nsp12 and S genes, more precisely at the nsp12/nsp13 junction. This study focuses on the sequences of the nsp12, S, and N genes of 15 HCoV-OC43s detected in respiratory specimens sampled from 2001 to 2013. In this study, all HCoV-OC43s including the VR759 prototype strain are associated with three accession numbers in GenBank, for nsp12, S, and N genes ( Table 1 ). cache = ./cache/cord-337707-xbwilp1w.txt txt = ./txt/cord-337707-xbwilp1w.txt === reduce.pl bib === id = cord-338589-1ent68fx author = Stoddard, Shana V. title = Optimization Rules for SARS-CoV-2 M(pro) Antivirals: Ensemble Docking and Exploration of the Coronavirus Protease Active Site date = 2020-08-26 pages = extension = .txt mime = text/plain words = 11437 sentences = 606 flesch = 55 summary = The ensemble docking and characterization work described in this article demonstrates the multifaceted features of the SARS-CoV-2 M(pro) active site, molecular guidelines to improving binding affinity, and ultimately the optimization of drug candidates. After optimization efforts using the design guidelines developed from the molecular docking studies, the average docking score of the parent compounds was improved by 6.59 −log(10)(Kd) in binding affinity which represents an increase of greater than six orders of magnitude. The results of molecular dynamic (MD) simulation of cinanserin-optimized compounds CM02, CM06, and CM07 revealed that CM02 and CM06 fit well into the active site of SARS-CoV-2 M(pro) [Protein Data Bank (PDB) accession number 6LU7] and formed strong and stable interactions with the key residues, Ser-144, His-163, and Glu-166. The use of multiple conformations when using docking will assist in the prediction of new antivirals agents targeting SARS-CoV-2 M pro as the diversity of accessible variations can produce distinct binding poses for an inhibitor compound. cache = ./cache/cord-338589-1ent68fx.txt txt = ./txt/cord-338589-1ent68fx.txt === reduce.pl bib === id = cord-338436-0z828org author = Tzou, Philip L. title = Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date = 2020-09-09 pages = extension = .txt mime = text/plain words = 8193 sentences = 522 flesch = 46 summary = Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. Figure 4 displays EC 50 values for many of the directly acting antiviral compounds currently in clinical trials for the treatment of COVID-19 including six polymerase inhibitors (remdesivir, EIDD-2801, favipiravir, ribavirin, galidesivir, and sofosbuvir), three HIV-1 protease inhibitors (lopinavir, atazanavir, and darunavir), and three entry inhibitors (receptor binding monoclonal antibodies, soluble recombinant human ACE2, and umifenovir). Viruses 2020, 12, x FOR PEER REVIEW 11 of 22 Table 4 describes a set of the most promising compounds for the treatment of SARS-CoV-2 based on the following criteria: (i) act by a validated direct or indirect antiviral mechanism, (ii) display submicromolar activity in vitro and/or inhibitory activity in an animal model, and (iii) have a record of safety and favorable pharmacokinetics in human subjects. cache = ./cache/cord-338436-0z828org.txt txt = ./txt/cord-338436-0z828org.txt === reduce.pl bib === id = cord-338811-2bi2edcw author = Lennemann, Nicholas J. title = Imaging-Based Reporter Systems to Define CVB-Induced Membrane Remodeling in Living Cells date = 2020-09-25 pages = extension = .txt mime = text/plain words = 6671 sentences = 327 flesch = 43 summary = To define the dynamic process of enterovirus membrane remodeling of major secretory pathway organelles, we have developed plasmid-based reporter systems that utilize viral protease-dependent release of a nuclear-localized fluorescent protein from the endoplasmic reticulum (ER) membrane during infection, while retaining organelle-specific fluorescent protein markers such as the ER and Golgi. To monitor enterovirus infection in real-time, we adapted cell-based reporter methodologies previously used for flaviviruses and hepatitis C virus that rely on viral protease cleavage-dependent translocation of a membrane-anchored cytoplasmic fluorescent proteins to the nucleus [27] [28] [29] . CVB infection of RepER expressing U2OS cells resulted in a clear translocation of GFP-NLS reporter to the nucleus and eventual dispersal due to cell lysis, while the mCherry-KDEL was maintained in the membranous structure of the ER (Video S1 and Figure 2a) . Live-cell imaging of CVB infected cells expressing these reporters allowed for the real-time visualization of virus-induced changes to the host cell, including the collapse of the peripheral ER network and loss of Golgi integrity. cache = ./cache/cord-338811-2bi2edcw.txt txt = ./txt/cord-338811-2bi2edcw.txt === reduce.pl bib === id = cord-341968-uc8i9h0m author = Izaguirre, Gonzalo title = The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases date = 2019-09-09 pages = extension = .txt mime = text/plain words = 7870 sentences = 410 flesch = 45 summary = A wide variety of viruses exploit furin and other proprotein convertases (PCs) of the constitutive protein secretion pathway in order to regulate their cell entry mechanism and infectivity. Like other enveloped viruses that rely on surface glycoproteins for binding and fusion, coronaviruses have the Spike (S) protein, which is cleaved by proteases during virion biosynthesis, as well as during entry into target cells [53] . The location of furin and related PCs in the vesicles of the constitutive protein secretion pathway, where viruses are assembled during morphogenesis or disassembled during cell entry, explains why a diversity of virus types have evolutionarily converged to depend on PCs. Viruses also use other types of proteases for the proteolytic regulation of the binding and fusion functions; however, proteases are restricted to specific cell types, which limits the range of the viral infection, so when some viruses mutate and acquire PC reactivity, they may expand their cell tropism and become more pathogenic. cache = ./cache/cord-341968-uc8i9h0m.txt txt = ./txt/cord-341968-uc8i9h0m.txt === reduce.pl bib === id = cord-339752-o6atz33c author = Xiao, Li title = ACE2: The Key Molecule for Understanding the Pathophysiology of Severe and Critical Conditions of COVID-19: Demon or Angel? date = 2020-04-28 pages = extension = .txt mime = text/plain words = 3937 sentences = 257 flesch = 49 summary = According to a report based on 72,314 cases (test confirmed cases: 44,672 (62%) from the Chinese Center for Disease Control and Prevention, 81% of COVID-19 patients have cold-like symptoms and mild pneumonia, 14% have severe respiratory inflammation, and 5% have critical conditions including respiratory failure, septic shock, and/or multiple organ dysfunction or failure. Similar to SARS (severe acute respiratory syndrome, [2002] [2003] coronavirus (SARS-CoV) [3] , SARS-CoV-2 primarily uses the S protein to invade host cells through ACE2, an enzyme which is known to be important in the renin-angiotensin-aldosterone system (RAAS) [4, 5] . Since TMPRSS2 plays a very important role in SARS-CoV-2 cell entry and ACE2 dysfunction, blocking the activity of TMPRSS2 should be the primary strategy for preventing severe and critical conditions of COVID-19. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) cache = ./cache/cord-339752-o6atz33c.txt txt = ./txt/cord-339752-o6atz33c.txt === reduce.pl bib === id = cord-341138-mxjsp3cm author = Denner, Joachim title = Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV) date = 2016-12-20 pages = extension = .txt mime = text/plain words = 4762 sentences = 239 flesch = 47 summary = title: Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV) The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. The transspecies transmission of the gibbon ape leukaemia virus (GaLV) and the koala retrovirus (KoRV) is a prime example of a transmission that is still not yet fully understood. Searching for the precursor virus, retroviruses related to KoRV and GaLV have been described in rodents such as South East Asian mice (e.g., Mus caroli [9, 10] and Mus dunni [11] ), as well as in two subspecies of Melomys burtoni in Australia and Indonesia [12, 13] . The nucleotide sequence of koala (Phascolarctos cinereus) retrovirus: A novel type C endogenous virus related to gibbon ape leukemia virus cache = ./cache/cord-341138-mxjsp3cm.txt txt = ./txt/cord-341138-mxjsp3cm.txt === reduce.pl bib === id = cord-338973-73a7uvyz author = Xu, Jiabao title = Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV date = 2020-02-22 pages = extension = .txt mime = text/plain words = 7110 sentences = 426 flesch = 57 summary = After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The source of unexplained pneumonia was first discovered in Wuhan in Dec, 2019, and SARS-CoV-2, a new coronavirus, was isolated from the respiratory epithelium of patients. Hong Kong scholars found that, compared with ribavirin alone, patients treated with lopinavir/ritonavir and ribavirin had lower risk of acute respiratory distress syndrome (ARDS) or death caused by SARS-CoV [76, 77] . A high-resolution crystal structure of SARS-CoV-2 coronavirus 3CL hydrolase (Mpro) was announced after the outbreak of COVID-19 in the world [80] , and human coronaviruses (HCoVs) have been treated as severe pathogens in respiratory tract infections. cache = ./cache/cord-338973-73a7uvyz.txt txt = ./txt/cord-338973-73a7uvyz.txt === reduce.pl bib === id = cord-342130-eo4le4v3 author = Qin, Pan title = Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy date = 2019-05-18 pages = extension = .txt mime = text/plain words = 4029 sentences = 209 flesch = 46 summary = title: Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy PDCoV infection also increased the number of autophagosome-like vesicles in the cytoplasm of cells, and the autophagy response was detected by LC3 I/II and p62 Western blot analysis. Double-membraned autophagosomes-like vesicles were detected in PDCoV-infected cells at 12 hpi and increased thereafter. In summary, we demonstrate and elaborate some novel, in vitro characteristics of the life cycle of PDCoV, including replication kinetics in cultured cells, cellular ultrastructure, virion morphology, and possible induction of autophagy, mainly by means of EM observation. In summary, we demonstrate and elaborate some novel, in vitro characteristics of the life cycle of PDCoV, including replication kinetics in cultured cells, cellular ultrastructure, virion morphology, and possible induction of autophagy, mainly by means of EM observation. cache = ./cache/cord-342130-eo4le4v3.txt txt = ./txt/cord-342130-eo4le4v3.txt === reduce.pl bib === id = cord-342739-iy9vjpuh author = Schwartz, David A. title = Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections date = 2020-02-10 pages = extension = .txt mime = text/plain words = 8414 sentences = 406 flesch = 49 summary = In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. The most common adverse obstetrical outcomes associated with maternal pneumonias from all causes include This newly recognized coronavirus, producing a disease that has been termed COVID-19, is rapidly spreading throughout China, has crossed international borders to infect persons in neighboring countries, and humans infected by the virus are travelling via commercial airlines to other continents. Pregnant women may develop severe disease and fatal maternal and/or fetal outcomes as a result of MERS-CoV infection; however, little is known of the pathophysiology of this infection during pregnancy. cache = ./cache/cord-342739-iy9vjpuh.txt txt = ./txt/cord-342739-iy9vjpuh.txt === reduce.pl bib === id = cord-342923-prgorr3d author = Li, Zhonghua title = Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication date = 2018-03-13 pages = extension = .txt mime = text/plain words = 4170 sentences = 266 flesch = 56 summary = title: Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication Replication of PEDV was inhibited by silencing the expression of hnRNP A1 in CCL-81 cells, suggesting the positive effect of hnRNP A1 on PEDV infection. Previous studies have demonstrated hnRNP A1 could interact with N proteins of SARS Coronavirus and mouse hepatitis virus (MHV) [14, 19] . Our previous work has proved that hnRNP A1 underwent different regulations in jejunum tissues of piglets infected with PEDV virulent strain and its attenuated strain [20] . The beads were then washed with IP lysis buffer five times and boiled in sample buffer, and the proteins were subjected to SDS-PAGE, followed by immunoblotting analysis with anti-Flag PAb or anti-hnRNP A1 PAb. CCL-81 cells grown on coverslips were infected with PEDV YN144 strain, YN13 strain and CV777 strain, respectively, at a multiplicity of infection (MOI) 0.001. cache = ./cache/cord-342923-prgorr3d.txt txt = ./txt/cord-342923-prgorr3d.txt === reduce.pl bib === id = cord-343690-rafvxgx1 author = Hartmann, Katrin title = Clinical Aspects of Feline Retroviruses: A Review date = 2012-10-31 pages = extension = .txt mime = text/plain words = 10289 sentences = 498 flesch = 35 summary = Although FIV can cause an acquired immunodeficiency syndrome in cats ("feline AIDS") comparable to human immunodeficiency virus (HIV) infection in humans, with increased risk for opportunistic infections, neurologic diseases, and tumors, in most naturally infected cats, FIV does not cause a severe clinical syndrome. Experimental FIV infection also progresses through several stages, similar to HIV infection in people, including an acute phase, a clinically asymptomatic phase of variable duration, and a terminal phase sometimes called "feline acquired immunodeficiency syndrome" ("AIDS") [18, 19] . Of 8642 FeLV-infected cats presented to North American Veterinary Teaching Hospitals, various co-infections (including FIV infection, feline infectious peritonitis (FIP), upper respiratory infection, hemotropic mycoplasmosis, and stomatitis) were the most frequent findings (15%), followed by anemia (11%), lymphoma (6%), leukopenia or thrombocytopenia (5%), and leukemia or myeloproliferative diseases (4%) [20] . An early defect in primary and secondary t cell responses in asymptomatic cats during acute feline immunodeficiency virus (fiv) infection cache = ./cache/cord-343690-rafvxgx1.txt txt = ./txt/cord-343690-rafvxgx1.txt === reduce.pl bib === id = cord-345472-qrddwebe author = Sebina, Ismail title = The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis date = 2020-07-27 pages = extension = .txt mime = text/plain words = 8184 sentences = 411 flesch = 28 summary = A vaccine against respiratory syncytial virus (RSV), the leading cause of viral bronchiolitis in infancy, remains elusive, and hence new therapeutic modalities are needed to limit disease severity. (1), degranulation (2), respiratory oxygen species (ROS) production (3), and the release of neutrophil extracellular traps (NETosis) (4) are associated with increased lung inflammation, systemic fever, mucus hypersecretion, airway obstruction, and epithelial cell death. Excessive neutrophil-derived inflammatory cytokine production (1), degranulation (2), respiratory oxygen species (ROS) production (3), and the release of neutrophil extracellular traps (NETosis) (4) are associated with increased lung inflammation, systemic fever, mucus hypersecretion, airway obstruction, and epithelial cell death. Unlike wild-type (WT) control mice, plasmacytoid dendritic cell (pDC)-depleted, Toll-like receptor (TLR)7-deficient, or interferon regulatory factor (IRF)7-deficient neonatal mice develop severe pathology, characterised by increased neutrophilia and lung inflammation in response to acute PVM infection [80] [81] [82] . cache = ./cache/cord-345472-qrddwebe.txt txt = ./txt/cord-345472-qrddwebe.txt === reduce.pl bib === id = cord-345651-admlzeu4 author = Wang, Gang title = The N-Terminal Domain of Spike Protein Is Not the Enteric Tropism Determinant for Transmissible Gastroenteritis Virus in Piglets date = 2019-03-30 pages = extension = .txt mime = text/plain words = 6220 sentences = 265 flesch = 49 summary = Using a novel approach, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems efficiently and rapidly rescued another recombinant virus with a 224-amino-acid deletion in the N-terminal domain of the TGEV Spike gene (S_NTD224), which is analogous to the N-terminal domain of porcine respiratory coronavirus. Homologous recombination was then performed using the ClonExpress II One Step Cloning Kit (Vazyme, Nanjing, Jiangsu, China) according to the manufacturer's instructions using 200 ng of recycled linearized pTGEV-GFP BAC, 45 ng of PCR products of S_NTD and two pairs of primers (rec-672SF/δS-NTDR and rec-672SR/δS-NTDF) ( Table 2) . To construct an infectious clone of TGEV, six overlapping cDNA fragments designated A to F were generated by reverse transcriptase PCR (RT-PCR) using total RNA extracted from PK-15 cells infected with TGEV WH-1 ( Figure 1A ,B). Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus cache = ./cache/cord-345651-admlzeu4.txt txt = ./txt/cord-345651-admlzeu4.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-347362-e4paw26n author = Klein-Richers, Ute title = Prevalence of Feline Coronavirus Shedding in German Catteries and Associated Risk Factors date = 2020-09-08 pages = extension = .txt mime = text/plain words = 4605 sentences = 216 flesch = 50 summary = The aim of this prospective study was to determine prevalence and potential risk factors of feline coronavirus (FCoV) shedding. Four consecutive fecal samples of 179 cats from 37 German breeding catteries were analyzed for FCoV ribonucleic acid (RNA) by real-time reverse transcriptase polymerase chain reaction (RT-qPCR). Therefore, the aim of this study was to determine the prevalence of FCoV shedding in German breeding catteries and to evaluate associated risk factors. The number of cats per cattery, breed, hygiene management, husbandry conditions and outdoor access were not significantly associated with FCoV shedding in this population (Tables 4 and 5 ). Univariate risk factor analysis in the present study suggested that breed and the number of cats in the household had a significant influence on the prevalence of FCoV shedding, but these results have been distorted by the effect each breeder has on hygienic conditions and the risk of infection within their cattery. cache = ./cache/cord-347362-e4paw26n.txt txt = ./txt/cord-347362-e4paw26n.txt === reduce.pl bib === id = cord-347053-m5m4zgfy author = Pharo, Elizabeth A. title = Host–Pathogen Responses to Pandemic Influenza H1N1pdm09 in a Human Respiratory Airway Model date = 2020-06-24 pages = extension = .txt mime = text/plain words = 9450 sentences = 554 flesch = 50 summary = wdNHBE cells produced an innate immune response to IAV-infection with increased transcription of proand anti-inflammatory cytokines and chemokines and the antiviral viperin but reduced expression of the mucin-encoding MUC5B, which may impair mucociliary clearance. The cytopathic effect of H1N1pdm09 included damage to the airway epithelium, the induction of innate immune responses including the expression of pro-and anti-inflammatory cytokines and chemokines and antiviral genes and proteins, consistent with pulmonary host defense. Key genes upregulated in our H1N1pdm09 in vitro challenge model, mimic the innate immune and inflammatory response in human patients in vivo infected with the 2009 pandemic IAV. The more than 350-fold induction of the antiviral-encoding RSAD2 (viperin) gene in our pandemic IAV-infected wdNHBE cells confirms the antiviral response of the airway epithelium in vitro. The disruption of the airway epithelium by IAV H1N1pdm09 and poly(I:C), plus the induction of the innate immune response and antiviral, and pro-and anti-inflammatory genes demonstrated the viability of this model to investigate pandemic influenza. cache = ./cache/cord-347053-m5m4zgfy.txt txt = ./txt/cord-347053-m5m4zgfy.txt === reduce.pl bib === id = cord-348968-0yoq0geu author = Zhang, Maodong title = Assessment of Metagenomic Sequencing and qPCR for Detection of Influenza D Virus in Bovine Respiratory Tract Samples date = 2020-07-28 pages = extension = .txt mime = text/plain words = 5718 sentences = 270 flesch = 46 summary = The objective of this study was to assess the detection of influenza D virus (IDV) in bovine respiratory tract samples using two sequencing platforms (MiSeq and Nanopore (GridION)), and species-specific qPCR. In this study, IDV was used as a representative BRD-associated virus to examine the feasibility of using metagenomic sequencing for detection of viruses in clinical bovine respiratory samples. The proportion of viral reads per sample was 0.1% to 18.4% (Nanopore, WIMP analysis) compared to 0.03% to 3.1% for the previously generated MiSeq data; however, with both sequencing approaches, the majority of reads obtained were identified as host-derived or other (bacteria, fungi, unclassified) ( Figure 3 ). Taken together our results demonstrate the potential of metagenomic sequencing on the Illumina MiSeq and Oxford Nanopore platforms for detection of viruses, including IDV, in clinical samples from naturally infected animals with a wide range of viral loads. cache = ./cache/cord-348968-0yoq0geu.txt txt = ./txt/cord-348968-0yoq0geu.txt === reduce.pl bib === id = cord-349011-kxhpdvri author = Grandvaux, Nathalie title = CSV2018: The 2nd Symposium of the Canadian Society for Virology date = 2019-01-18 pages = extension = .txt mime = text/plain words = 8844 sentences = 375 flesch = 42 summary = Invited keynote speakers included David Kelvin (Dalhousie University and Shantou University Medical College) who provided a historical perspective on influenza on the 100th anniversary of the 1918 pandemic; Sylvain Moineau (Université Laval) who described CRISPR-Cas systems and anti-CRISPR proteins in warfare between bacteriophages and their host microbes; and Kate O'Brien (then from Johns Hopkins University, now relocated to the World Health Organization where she is Director of Immunization, Vaccines and Biologicals), who discussed the underlying viral etiology for pneumonia in the developing world, and the evidence for respiratory syncytial virus (RSV) as a primary cause. The "Viral Subversion of Host Cell Processes" session also included presentations from the following trainees: Nichole McMullen (Dalhousie University) who reported the unconventional egress mechanisms of non-enveloped reoviruses, Justine Sitz (Université Laval) who described interactions between a human papillomavirus protein and a host DNA repair-specific E3 ubiquitin ligase, and Quentin Osseman (Université de Montréal) who described interactions between respiratory syncytial virus (RSV) and the host autophagy pathway. cache = ./cache/cord-349011-kxhpdvri.txt txt = ./txt/cord-349011-kxhpdvri.txt === reduce.pl bib === id = cord-349560-8n65rgfz author = Kleines, Michael title = WU Polyomavirus (WUPyV): A Recently Detected Virus Causing Respiratory Disease? date = 2009-11-04 pages = extension = .txt mime = text/plain words = 4053 sentences = 230 flesch = 45 summary = The WU polyomavirus (WUPyV) is a novel member of the family Polyomaviridae recently detected in respiratory tract specimens by shotgun sequencing. Creer and co-workers [1] identified at least one potential pathogen in 69% of specimens from adults suffering from lower respiratory tract infections (LRTI, 63% contained viruses, 26% contained bacteria) still leaving a significant diagnostic gap to be filled with so far unidentified pathogenic microorganisms. For this reason, detection of virus-specific antibodies by complement fixation assays, enzyme linked immunosorbent assays (ELISA), or immunofluorescence assays (IFA), all of which are available for established respiratory viruses, is inappropriate for the identification of the etiologic agent causing an acute respiratory tract infection, but useful for retrospective or epidemiological studies. Following the discovery of WUPyV in Australia, the virus was detected in specimens from patients with respiratory tract disease on all continents suggesting a worldwide distribution [10, [29] [30] [31] . cache = ./cache/cord-349560-8n65rgfz.txt txt = ./txt/cord-349560-8n65rgfz.txt === reduce.pl bib === id = cord-349117-xfir3m5p author = Hyseni, Inesa title = Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays date = 2020-09-10 pages = extension = .txt mime = text/plain words = 8298 sentences = 403 flesch = 52 summary = After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study. SARS CoV-2 strain 2019-nCov/Italy wild-type virus (LV), which was handled in a level 3 bio-containment facility (BSL 3), was used as positive control in order to evaluate the spike glycoprotein expression, while a ∆-envelope pseudotype, prepared with the same procedure, was used as a negative control. To verify the expression of the spike protein in the SARS-CoV-2 pseudotypes, the spike was detected by Western blot; sera from convalescent SARS-CoV-2 patients, which have been shown to have a high neutralising titre in microneutralisation with a live virus, were used as the primary antibody, and goat anti-Human IgG as the secondary antibody. cache = ./cache/cord-349117-xfir3m5p.txt txt = ./txt/cord-349117-xfir3m5p.txt === reduce.pl bib === id = cord-350964-0jtfc271 author = Van Nguyen, Dung title = Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam date = 2018-02-28 pages = extension = .txt mime = text/plain words = 4803 sentences = 246 flesch = 51 summary = In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Nucleic acid that was extracted from liver samples of 157 bats (29 species; Table S1 ) and 470 rodents (six species) was screened for pegivirus and human hepatitis B, C, E viruses and their homologues ( Table 1 ) by nested and semi-nested PCR assays with degenerate primers. cache = ./cache/cord-350964-0jtfc271.txt txt = ./txt/cord-350964-0jtfc271.txt === reduce.pl bib === id = cord-351228-hpo8bboi author = Wasilenko, Shawn T. title = Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis? date = 2013-01-24 pages = extension = .txt mime = text/plain words = 4260 sentences = 210 flesch = 36 summary = Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. Nevertheless, a major conclusion of most series documenting outcomes in patients with PBC following liver transplantation is that CsA is associated with a lower incidence of recurrent disease [10] [11] [12] [13] [14] [15] [16] 18] . Other agents, such as hepatitis C virus (HCV) rely on cyclophilin A interactions with viral components of the replication complex to produce RNA transcripts, a process also blocked by CsA [64] [65] [66] [67] [68] [69] [70] [71] . Cyclosporine A protects against primary biliary cirrhosis recurrence after liver transplantation Long-term follow-up after recurrence of primary biliary cirrhosis after liver transplantation in 100 patients De novo autoimmune hepatitis following liver transplantation for primary biliary cirrhosis cache = ./cache/cord-351228-hpo8bboi.txt txt = ./txt/cord-351228-hpo8bboi.txt === reduce.pl bib === id = cord-351365-dc9t3vh3 author = Todt, Daniel title = Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations date = 2016-10-13 pages = extension = .txt mime = text/plain words = 6318 sentences = 320 flesch = 40 summary = Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis. Figure 1 provides an overview of a selection of RNA viruses against which RBV was shown to be active: hepatitis C virus (HCV, Flaviviridae), dengue virus (DENV, Flaviviridae), respiratory syncytial virus (RSV, Paramyxoviridae), influenza A and B virus (Orthomyxoviridae), chikungunya virus (CHIKV, Togaviridae), poliovirus (Picornaviridae), Hantaan virus (Bunyaviridae), and Lassa virus (Arenaviridae) [28, 29] ( Figure 1 ). Furthermore, mechanisms on the virus itself were described by inhibition of the capping efficiency, the viral polymerase, and a mutagenic effect on newly synthesized RNA genomes. A Mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients cache = ./cache/cord-351365-dc9t3vh3.txt txt = ./txt/cord-351365-dc9t3vh3.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 === id = cord-351377-xorj8tnz author = Kao, Chi-Fei title = The Characterization of Immunoprotection Induced by a cDNA Clone Derived from the Attenuated Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strain date = 2018-10-04 pages = extension = .txt mime = text/plain words = 5936 sentences = 234 flesch = 48 summary = Moreover, inoculation with iPEDVPT-P96 elicited comparable levels of anti-PEDV specific plasma IgG and fecal/salivary IgA, neutralizing antibody titers, and similar but less effective immunoprotection against the virulent PEDVPT-P5 challenge compared to the parental PEDVPT-P96. In the present study, an infectious cDNA clone of an attenuated G2b PEDV strain was successfully generated for the first time, and the in vitro and in vivo data indicate that iPEDVPT-P96 is further attenuated but remains immunogenic compared to its parental PEDVPT-P96 viral stock. While one piglet in the PEDVPT-P96 group showed intermittent loose diarrhea (score = 1) and viral shedding at 6 to 11 days post-inoculation (DPI) with the peak viral titer of 1.45 ± 3.24 log 10 RNA copies/mL at 8 DPI (Figure 4) , no evidence of PEDV-associated clinical signs and fecal viral shedding were demonstrated in both iPEDVPT-P96 and mock groups. cache = ./cache/cord-351377-xorj8tnz.txt txt = ./txt/cord-351377-xorj8tnz.txt === reduce.pl bib === id = cord-351955-9l4786lb author = Pedersen, Niels C. title = Significance of Coronavirus Mutants in Feces and Diseased Tissues of Cats Suffering from Feline Infectious Peritonitis date = 2009-08-26 pages = extension = .txt mime = text/plain words = 6785 sentences = 322 flesch = 58 summary = Complete structural (S, E, M, N) and accessory (3a-c and 7 a, b) gene sequences were obtained from diseased omentum of the four related cats that died of FIP and the isolates designated were FIPV-UCD11, 12, 13 and 14 ( Table 1 ). The coronavirus isolated from Lucy's feces (designated FECV-UCD3) had an intact (i.e., wild type or non-deliterious) 3c and its sequence was otherwise 99% identical to the sequence of FIPV-UCD14 found in her diseased omentum. FECV-UCD4, was most closely related to the FIPV isolated from Lucy and was 99.7% related to the consensus nucleotide sequences of coronaviruses obtained from the four related FIP cats ( Figure 1 , Table 2 ). The 3c gene sequence of the fecal virus of cat 388406 was intact and ≥99% related to the FIPV found in diseased tissue ( Table 2 ). cache = ./cache/cord-351955-9l4786lb.txt txt = ./txt/cord-351955-9l4786lb.txt === reduce.pl bib === id = cord-351760-698voi9y author = Han, Hui-Ju title = Neutralizing Monoclonal Antibodies as Promising Therapeutics against Middle East Respiratory Syndrome Coronavirus Infection date = 2018-11-30 pages = extension = .txt mime = text/plain words = 4144 sentences = 206 flesch = 49 summary = The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. In vivo study demonstrated that prophylaxis with m336 reduced virus titers in the lung of rabbits infected with MERS-CoV [15] , and m336 also provided transgenic mice expressing human DPP4 with full prophylactic and therapeutic protection from MERS-CoV [16] . A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein Prophylaxis with a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection Passive Transfer of a Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV cache = ./cache/cord-351760-698voi9y.txt txt = ./txt/cord-351760-698voi9y.txt === reduce.pl bib === id = cord-352527-eeyqh9nc author = Zhou, Yusen title = Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain date = 2019-01-14 pages = extension = .txt mime = text/plain words = 5834 sentences = 277 flesch = 44 summary = A number of MERS vaccines have been developed based on viral RBD, including nanoparticles, virus-like particles (VLPs), and recombinant proteins, and their protective efficacy has been evaluated in animal models, including mice with adenovirus 5 (Ad5)-directed expression of human DPP4 (Ad5/hDPP4), hDPP4-transgenic (hDPP4-Tg) mice, and non-human primates (NHPs) [88] [89] [90] [91] [92] [93] [94] . Receptor usage of a novel bat lineage C Betacoronavirus reveals evolution of Middle East respiratory syndrome-related coronavirus spike proteins for human dipeptidyl peptidase 4 binding Recombinant receptor-binding domains of multiple Middle East respiratory syndrome coronaviruses (MERS-CoVs) induce cross-neutralizing antibodies against divergent human and camel MERS-CoVs and antibody escape mutants A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein A novel nanobody targeting Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain has potent cross-neutralizing activity and protective efficacy against MERS-CoV cache = ./cache/cord-352527-eeyqh9nc.txt txt = ./txt/cord-352527-eeyqh9nc.txt === reduce.pl bib === id = cord-352007-3djwbivp author = Xiang, Qi title = Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication date = 2020-07-14 pages = extension = .txt mime = text/plain words = 6873 sentences = 353 flesch = 48 summary = Here, we primarily found that Beclin1 facilitates EV71 replication in human rhabdomyosarcoma (RD) cells and the autophagy was actually induced, but Beclin1 was not significantly affected at either mRNA level or protein level during early EV71 infection. The results show that the mRNA level and protein level of Beclin1 were significantly reduced in RD cells; moreover, knockdown of BECN1 inhibited EV71 replication ( Figure 3A,B) . Our group has previously reported several host factors regulating EV71 replication; for example, SIRT1 can inhibit EV71 replication and RNA translation by interfering with the viral polymerase and 5 UTR RNA [57] , and PolyC-Binding Protein 1 interacts with 5 -untranslated region of EV71 RNA in membrane-associated complex to facilitate viral replication [58] . In FMDV (Foot-and-mouth disease virus)-infected cells, the largest viral protein in the replication complex, 2C, would bind to Beclin1 to prevent the fusion of lysosomes to autophagosomes, allowing for virus survival [35] . cache = ./cache/cord-352007-3djwbivp.txt txt = ./txt/cord-352007-3djwbivp.txt === reduce.pl bib === id = cord-353365-ujz5nkk3 author = Pirnay, Jean-Paul title = Study of a SARS-CoV-2 Outbreak in a Belgian Military Education and Training Center in Maradi, Niger date = 2020-08-27 pages = extension = .txt mime = text/plain words = 4773 sentences = 246 flesch = 53 summary = The medical military command implemented testing of all Belgian soldiers for SARS-CoV-2 viral load and antibodies, two to three days before their departure on a mission abroad or on the high seas, and for specific missions immediately upon their return in Belgium. The SARS-CoV-2 outbreak in a Belgian military education and training center in Maradi, Niger, was characterized by mild symptoms in five soldiers and asymptomatic infection in two soldiers (one trainer), both having a viral load, as diagnosed upon their timely return to Belgium. The SARS-CoV-2 outbreak in a Belgian military education and training center in Maradi, Niger, was characterized by mild symptoms in five soldiers and asymptomatic infection in two soldiers (one trainer), both having a viral load, as diagnosed upon their timely return to Belgium. cache = ./cache/cord-353365-ujz5nkk3.txt txt = ./txt/cord-353365-ujz5nkk3.txt === reduce.pl bib === id = cord-352619-s2x53grh author = Payne, Natalie title = Novel Circoviruses Detected in Feces of Sonoran Felids date = 2020-09-15 pages = extension = .txt mime = text/plain words = 3263 sentences = 177 flesch = 45 summary = Genomes from several families of circular Rep-encoding single-stranded DNA viruses (CRESS-DNA viruses) are part of the phylum Cressdnaviricota [22] and have been identified in fecal samples of other mammals, including domestic cats [23, 24] , bobcats, African lions [25] , capybaras [26] , and Tasmanian devils [27] . Here we used a metagenomic approach to identify novel circoviruses in the feces of two species of Sonoran felids, the puma and bobcat; although not endangered, knowledge of viral threats facing these species could help prevent future population decline, as well as indicate potential threats to the endangered ocelot and jaguar. Based on the species-demarcation threshold for circoviruses which is 80% genome-wide identity [28] , both of these belong to a new species which we refer to as Sonfela (derived from Sonoran felid associated) circovirus 1. As the viral genomes were derived from scat samples, the circoviruses could have infected the bobcat prey species or the felids themselves or be environmentally derived. cache = ./cache/cord-352619-s2x53grh.txt txt = ./txt/cord-352619-s2x53grh.txt === reduce.pl bib === id = cord-353609-no3mbg5d author = Vandegrift, Kurt J. title = An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses date = 2011-04-15 pages = extension = .txt mime = text/plain words = 6925 sentences = 350 flesch = 42 summary = Conducting viral surveillance in animal reservoirs and invertebrate vectors can help explain circulation within host species; observed patterns of zoonotic transmission; and even allow for the prediction of periods of increased risk of zoonotic transmission (e.g., Rift valley fever and rainfall [25] ; West Nile virus (WNV) and American robin (Turdus turdus) migration [26] ; as well as hantavirus in mice [27, 28] ). Globalization, host ecology, host-virus dynamics, climate change, and anthropogenic landscape changes all contribute to the complexity of zoonotic viral emergence and disease, and create significant conservation and public health challenges. While the lasting efficacy of wildlife vaccination efforts has yet to be demonstrated with either endangered species or in breaking the transmission cycle of human pathogens, an increasing number of researchers are drawing attention to systems where it seems feasible [99, 103] ; demonstrating that intricate knowledge of host and virus ecology can greatly reduce the amount of vaccine coverage that is necessary to control these viruses. cache = ./cache/cord-353609-no3mbg5d.txt txt = ./txt/cord-353609-no3mbg5d.txt === reduce.pl bib === id = cord-354068-4qlk6y7h author = Friedrich, Brian M. title = Potential Vaccines and Post-Exposure Treatments for Filovirus Infections date = 2012-09-21 pages = extension = .txt mime = text/plain words = 10605 sentences = 540 flesch = 44 summary = Due to the difficulties in evaluating wild-type filovirus infection in small animals and the generally high level of immune protection correlates derived from non-human primate (NHP) models of infection, therapeutics and vaccines are ultimately evaluated in NHP species for efficacy against filovirus. In their study, a heterologous prime/boost strategy with recombinant adenovirus serotypes 26 and 35 carrying GP (Z) and GP (S/G) demonstrated complete protection among NHPs. Each of these vectors was capable of stimulating humoral and cell-mediated immune responses in the context of NHPs pre-vaccinated with rAd5 as evidenced by antibody titers reaching an order of magnitude above those achieved in rAd5 vaccinated subjects (1:32,000 compared to 1:6,800), and CD8 + intracellular cytokine staining was 4.7-fold greater among heterologous prime/boosted subjects (0.41% compared to 0.09%) [59] . This GP-Fc fusion protein induced both cell-mediated and humoral immune responses, and mice vaccinated with ZEBOVGP-Fc demonstrated 90% protection against a lethal EBOV challenge. cache = ./cache/cord-354068-4qlk6y7h.txt txt = ./txt/cord-354068-4qlk6y7h.txt === reduce.pl bib === id = cord-354738-4rxradwz author = Kohl, Claudia title = European Bats as Carriers of Viruses with Zoonotic Potential date = 2014-08-13 pages = extension = .txt mime = text/plain words = 4797 sentences = 289 flesch = 52 summary = In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. Various publications reviewed bats globally as carriers and potential reservoir hosts of human-pathogenic and zoonotic viruses [3] [4] [5] [6] [7] [8] [9] [10] , while hardly anything is known about human-pathogenicity of European bat viruses apart from lyssaviruses. Similar to the case of the LLOV filovirus, virus isolates and prevalence studies in both humans and bats could improve knowledge and clarify their zoonotic potential. Sero-prevalence studies should be conducted on the orthoreoviruses isolated from European bats, especially as a closely related virus was detected in a diseased child in Slovenia [83] . Other bat viruses detected by using molecular techniques should be isolated (e.g., MERS-like CoV or Bat Bunyavirus) to allow for characterization and follow-up sero-prevalence studies. cache = ./cache/cord-354738-4rxradwz.txt txt = ./txt/cord-354738-4rxradwz.txt ===== Reducing email addresses Creating transaction Updating adr table ===== Reducing keywords cord-001972-1zisomq5 cord-001974-wjf3c7a7 cord-002590-24o2viv3 cord-000808-pxryt8wn cord-000804-0hlj6r10 cord-002589-xq3iq8ai cord-002076-7t4d4vvo cord-003407-f5v3hhr8 cord-003453-p2buyrcj cord-002994-1zjrunzc cord-003284-hjx2d5rq cord-003334-ion97n4b cord-002561-7j43yic1 cord-002691-synm1cyw cord-001831-3aonqyub cord-003586-afnto2tz cord-002808-84np9brx cord-003646-kjkuet78 cord-003516-l1lq8yga cord-001887-d6ycc8ci cord-003761-ikni2acz cord-004020-qtwcbn7m cord-003772-1345qct4 cord-003697-vmmlxr0o cord-003962-lg6gvgwt cord-003917-bswndfvk cord-003865-24lz9tf1 cord-003859-k8wfyj9b cord-003807-e2txo10z cord-004022-cr0zskcw cord-003775-1axsebya cord-003961-gs75ebo4 cord-004018-33zi29bg cord-003915-kje8lvgl cord-002185-oz7hras7 cord-003861-qeao4ghg cord-004337-jtaz1gdp cord-004334-y1fcw1dj cord-004335-bw3tziup cord-004509-jkzqmkz6 cord-009399-6zpkpdzu parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. cord-004510-cbutpjre cord-004508-ok3px98z cord-003130-p2h8p5bm cord-004507-ezuyjcxs cord-011435-x73foqu7 cord-011635-vosu7y6j cord-011438-imbpgsub cord-013174-whg64w0w cord-012845-so2umdlt cord-011436-ud35mf5l cord-012418-6ralcn8p cord-013177-whd0znan cord-012497-n5pu1yeu cord-012909-o6t2srim cord-012420-llh22iq2 cord-013178-li1x1m25 cord-252142-aqwlcs9g cord-253629-5aofwe1w cord-256713-tlluxd11 cord-254250-l0v602x9 cord-253282-zwl0safn cord-255683-2eq24jth cord-257665-12gyrmh2 cord-254181-nquozaxt cord-254596-wsmnlnlk cord-258323-vdeffy4l cord-257913-uf9sx5qi cord-256924-c7ftvgio cord-255607-dbexsugq cord-256370-cz88t29n cord-258536-qnn9hp8e cord-259658-rgrt6e6r cord-259237-aty0vrat cord-262434-q4tk96tq cord-262499-68vmdqky cord-260431-eksl7pp8 cord-259273-bh5csogu cord-261417-4pf5nsw2 cord-260705-huyyw5z6 cord-265679-7gzont7l cord-263200-ntq1f4ix cord-263142-o8qbqxhx cord-257539-01s21vh0 cord-259916-gr6v098c cord-267733-fuz8r3vj cord-267012-45tre8rn cord-267709-i2loz1xb cord-269249-7ubs3q6p cord-263315-g7os15m1 cord-260476-whfyczcj cord-266901-oyevbxtc cord-272018-txdc0c3j cord-272391-0imlae98 cord-263699-gosqpg3k cord-272459-w14finxf cord-281552-zfjy3m3i cord-273777-qb0vp9gr cord-273661-egpyvqrw cord-277039-yo5ojr0s cord-281837-knswbb2d cord-280782-8gbktpt3 cord-264526-bxpzo2xu cord-274569-jh0dyyz7 cord-279691-v5kpmk0b cord-270103-g9a72xf6 cord-257052-cik2wmlk cord-287647-0nyquokt cord-288058-oilurica cord-289273-zpyz1krq cord-272010-kc0gi3cj cord-273326-gmw8gl2r cord-292364-jhiimglg cord-284216-4sl8xfur cord-288556-o8i6j3b2 cord-268788-jcu3pasy cord-294347-axkdf5vu cord-272666-3uidpr79 cord-294125-v2dr4hm0 cord-296819-gztmidn2 cord-285935-5rsk6g7l cord-283756-ycjzitlk cord-258684-lq4knxgf cord-286343-s8n1ldol cord-290127-51ljxy72 cord-294842-aesiff1f cord-296736-jsm6o5pq cord-289757-jtvpfsiu cord-297339-et2305rz cord-292050-x3isowrt cord-301810-vtgdqart cord-301633-t8s4s0wo cord-295433-olmein3q cord-302716-wfla3l20 cord-307046-ko3bdvo0 cord-305857-2409me0p cord-297834-me1ajoyb cord-297092-oq14cwka cord-302953-gr2kk9w4 cord-300625-fvirvpyl cord-310579-tnxokfwu cord-309571-a0xu1d56 cord-252466-usrpodjx cord-308201-lavcsqov cord-311008-b7xjlqg3 cord-295044-eva0soja cord-310255-aixq5mhf cord-270380-1me7ugkg cord-309378-sfr1x0ob cord-311205-3uwiys4a cord-292948-1n5ej08f cord-315164-nidgnvvi cord-313439-cadyykks cord-312001-8p7scli8 cord-312272-g4n426cm cord-317587-rrx2r4n2 cord-306004-amv0los1 cord-317026-9zgc6xrb cord-307110-eiobmxp2 cord-309623-2ngr682l cord-309239-6lso1w0o cord-295750-0gpyi4ii cord-309693-f2htekhz cord-273366-xd84f8ct cord-313312-h607itv2 cord-317496-6o2upns3 cord-314340-ltx4w9zh cord-320212-fw51w4nm cord-310734-6v7oru2l cord-309635-1tgovkr7 cord-314505-7qh8dsew cord-313161-07iwwsfz cord-317037-1qydcc5e cord-317715-xtsi663k cord-314891-brgtwxhe cord-321080-pgxxkfc0 cord-320015-lbr2q4qh cord-321013-8pkrg0mx cord-321673-v5o49ees cord-322206-roxa3ix6 cord-321441-t1v0pu0w cord-320921-eumuid3r cord-323569-ksodnkic cord-323585-iv2dcpqj cord-324617-yok7mh70 cord-325574-4zf9qtlh cord-323995-cpn34j02 cord-326614-cik3ino6 cord-325823-bt7xo9iq cord-330475-mameyzih cord-328259-3g4klpyg cord-334027-xhfmio7k cord-332165-31tbc31x cord-332915-4o2dsf56 cord-330767-jja2wcfz cord-332576-pd62s65y cord-331094-22366b81 cord-334560-1j9zmuub cord-334134-fhie2m3u cord-331414-i0oxm5mr cord-335279-cfv18qn0 cord-336536-ie5ok0lz cord-335614-qh98622y cord-337707-xbwilp1w cord-337339-0vkigjv2 cord-338811-2bi2edcw cord-338436-0z828org cord-338589-1ent68fx cord-339752-o6atz33c cord-341968-uc8i9h0m cord-341138-mxjsp3cm cord-342923-prgorr3d cord-338973-73a7uvyz cord-342130-eo4le4v3 cord-342739-iy9vjpuh cord-334855-s0ci3r8w cord-345651-admlzeu4 cord-343690-rafvxgx1 cord-345472-qrddwebe cord-335567-ssnvr6nj cord-349011-kxhpdvri cord-347053-m5m4zgfy cord-350964-0jtfc271 cord-348968-0yoq0geu cord-349117-xfir3m5p cord-351228-hpo8bboi cord-351365-dc9t3vh3 cord-351377-xorj8tnz cord-351489-tzmev77c cord-352007-3djwbivp cord-353365-ujz5nkk3 cord-352619-s2x53grh cord-351955-9l4786lb cord-347362-e4paw26n cord-354068-4qlk6y7h cord-346836-6jyv0q5e cord-349560-8n65rgfz cord-354738-4rxradwz cord-352527-eeyqh9nc cord-353609-no3mbg5d cord-351760-698voi9y cord-326319-3538jmqd cord-328042-e1is656g Creating transaction Updating wrd table ===== Reducing urls cord-001974-wjf3c7a7 cord-003407-f5v3hhr8 cord-002994-1zjrunzc cord-003130-p2h8p5bm cord-003284-hjx2d5rq cord-003961-gs75ebo4 cord-003861-qeao4ghg cord-004020-qtwcbn7m cord-003807-e2txo10z cord-003516-l1lq8yga cord-004507-ezuyjcxs cord-011435-x73foqu7 cord-003915-kje8lvgl cord-004508-ok3px98z cord-003917-bswndfvk cord-003772-1345qct4 cord-003865-24lz9tf1 cord-013177-whd0znan cord-004334-y1fcw1dj cord-254596-wsmnlnlk cord-012909-o6t2srim cord-253629-5aofwe1w cord-264526-bxpzo2xu cord-254181-nquozaxt cord-262499-68vmdqky cord-013174-whg64w0w cord-259658-rgrt6e6r cord-009399-6zpkpdzu cord-263315-g7os15m1 cord-277039-yo5ojr0s cord-273366-xd84f8ct cord-273326-gmw8gl2r cord-288556-o8i6j3b2 cord-286343-s8n1ldol cord-270380-1me7ugkg cord-272666-3uidpr79 cord-292364-jhiimglg cord-292050-x3isowrt cord-300625-fvirvpyl cord-297092-oq14cwka cord-307110-eiobmxp2 cord-284216-4sl8xfur cord-308201-lavcsqov cord-314340-ltx4w9zh cord-314891-brgtwxhe cord-315164-nidgnvvi cord-317026-9zgc6xrb cord-317587-rrx2r4n2 cord-322206-roxa3ix6 cord-323995-cpn34j02 cord-311008-b7xjlqg3 cord-310734-6v7oru2l cord-324617-yok7mh70 cord-331094-22366b81 cord-328259-3g4klpyg cord-326319-3538jmqd cord-320212-fw51w4nm cord-334855-s0ci3r8w cord-336536-ie5ok0lz cord-337707-xbwilp1w cord-338436-0z828org cord-338811-2bi2edcw cord-338589-1ent68fx cord-342739-iy9vjpuh cord-342130-eo4le4v3 cord-347053-m5m4zgfy cord-350964-0jtfc271 cord-335614-qh98622y cord-348968-0yoq0geu cord-325823-bt7xo9iq cord-349117-xfir3m5p cord-338973-73a7uvyz cord-352527-eeyqh9nc cord-328042-e1is656g cord-351760-698voi9y cord-352619-s2x53grh cord-353365-ujz5nkk3 Creating transaction Updating url table ===== Reducing named entities cord-002590-24o2viv3 cord-001831-3aonqyub cord-003407-f5v3hhr8 cord-002561-7j43yic1 cord-001974-wjf3c7a7 cord-001887-d6ycc8ci cord-002691-synm1cyw cord-002808-84np9brx cord-002076-7t4d4vvo cord-003284-hjx2d5rq cord-000804-0hlj6r10 cord-003130-p2h8p5bm cord-002994-1zjrunzc cord-002185-oz7hras7 cord-003453-p2buyrcj cord-003586-afnto2tz cord-003516-l1lq8yga cord-002589-xq3iq8ai cord-001972-1zisomq5 cord-003646-kjkuet78 cord-003772-1345qct4 cord-003859-k8wfyj9b cord-003334-ion97n4b cord-003761-ikni2acz cord-003775-1axsebya cord-000808-pxryt8wn cord-003865-24lz9tf1 cord-004335-bw3tziup cord-004020-qtwcbn7m cord-003807-e2txo10z cord-009399-6zpkpdzu cord-004334-y1fcw1dj cord-003961-gs75ebo4 cord-003697-vmmlxr0o cord-003917-bswndfvk cord-004509-jkzqmkz6 cord-011436-ud35mf5l cord-004337-jtaz1gdp cord-004508-ok3px98z cord-013174-whg64w0w cord-004510-cbutpjre cord-004507-ezuyjcxs cord-011435-x73foqu7 cord-011635-vosu7y6j cord-011438-imbpgsub cord-012420-llh22iq2 cord-012497-n5pu1yeu cord-252466-usrpodjx cord-253629-5aofwe1w cord-256713-tlluxd11 cord-253282-zwl0safn cord-255683-2eq24jth cord-254181-nquozaxt cord-013177-whd0znan cord-004018-33zi29bg cord-252142-aqwlcs9g cord-003915-kje8lvgl cord-012418-6ralcn8p cord-012845-so2umdlt cord-013178-li1x1m25 cord-003962-lg6gvgwt cord-004022-cr0zskcw cord-003861-qeao4ghg cord-258323-vdeffy4l cord-255607-dbexsugq cord-012909-o6t2srim cord-254250-l0v602x9 cord-254596-wsmnlnlk cord-257539-01s21vh0 cord-258536-qnn9hp8e cord-258684-lq4knxgf cord-259237-aty0vrat cord-260431-eksl7pp8 cord-259273-bh5csogu cord-262499-68vmdqky cord-260705-huyyw5z6 cord-265679-7gzont7l cord-263315-g7os15m1 cord-260476-whfyczcj cord-267709-i2loz1xb cord-263699-gosqpg3k cord-267012-45tre8rn cord-267733-fuz8r3vj cord-263200-ntq1f4ix cord-262434-q4tk96tq cord-259916-gr6v098c cord-259658-rgrt6e6r cord-261417-4pf5nsw2 cord-264526-bxpzo2xu cord-268788-jcu3pasy cord-263142-o8qbqxhx cord-266901-oyevbxtc cord-257913-uf9sx5qi cord-257052-cik2wmlk cord-256924-c7ftvgio cord-272459-w14finxf cord-272010-kc0gi3cj cord-272018-txdc0c3j cord-256370-cz88t29n cord-273366-xd84f8ct cord-272391-0imlae98 cord-270103-g9a72xf6 cord-257665-12gyrmh2 cord-272666-3uidpr79 cord-270380-1me7ugkg cord-273777-qb0vp9gr cord-269249-7ubs3q6p cord-281552-zfjy3m3i cord-273661-egpyvqrw cord-277039-yo5ojr0s cord-279691-v5kpmk0b cord-274569-jh0dyyz7 cord-280782-8gbktpt3 cord-273326-gmw8gl2r cord-284216-4sl8xfur cord-281837-knswbb2d cord-287647-0nyquokt cord-285935-5rsk6g7l cord-289273-zpyz1krq cord-286343-s8n1ldol cord-288556-o8i6j3b2 cord-283756-ycjzitlk cord-288058-oilurica cord-292364-jhiimglg cord-289757-jtvpfsiu cord-290127-51ljxy72 cord-296736-jsm6o5pq cord-294347-axkdf5vu cord-292948-1n5ej08f cord-292050-x3isowrt cord-294125-v2dr4hm0 cord-294842-aesiff1f cord-295433-olmein3q cord-297092-oq14cwka cord-295044-eva0soja cord-295750-0gpyi4ii cord-296819-gztmidn2 cord-300625-fvirvpyl cord-301633-t8s4s0wo cord-297834-me1ajoyb cord-301810-vtgdqart cord-302716-wfla3l20 cord-309239-6lso1w0o cord-297339-et2305rz cord-307110-eiobmxp2 cord-305857-2409me0p cord-309623-2ngr682l cord-309693-f2htekhz cord-309571-a0xu1d56 cord-311008-b7xjlqg3 cord-310734-6v7oru2l cord-308201-lavcsqov cord-309378-sfr1x0ob cord-310579-tnxokfwu cord-302953-gr2kk9w4 cord-312272-g4n426cm cord-315164-nidgnvvi cord-314891-brgtwxhe cord-317496-6o2upns3 cord-317587-rrx2r4n2 cord-320212-fw51w4nm cord-317715-xtsi663k cord-314505-7qh8dsew cord-317037-1qydcc5e cord-317026-9zgc6xrb cord-306004-amv0los1 cord-311205-3uwiys4a cord-309635-1tgovkr7 cord-320921-eumuid3r cord-307046-ko3bdvo0 cord-313161-07iwwsfz cord-312001-8p7scli8 cord-321080-pgxxkfc0 cord-321673-v5o49ees cord-313312-h607itv2 cord-323569-ksodnkic cord-320015-lbr2q4qh cord-321013-8pkrg0mx cord-310255-aixq5mhf cord-322206-roxa3ix6 cord-321441-t1v0pu0w cord-314340-ltx4w9zh cord-325823-bt7xo9iq cord-326319-3538jmqd cord-328042-e1is656g cord-330767-jja2wcfz cord-330475-mameyzih cord-328259-3g4klpyg cord-326614-cik3ino6 cord-325574-4zf9qtlh cord-324617-yok7mh70 cord-323995-cpn34j02 cord-332576-pd62s65y cord-331094-22366b81 cord-332915-4o2dsf56 cord-331414-i0oxm5mr cord-313439-cadyykks cord-335567-ssnvr6nj cord-337707-xbwilp1w cord-338589-1ent68fx cord-334855-s0ci3r8w cord-332165-31tbc31x cord-335614-qh98622y cord-334560-1j9zmuub cord-334027-xhfmio7k cord-334134-fhie2m3u cord-337339-0vkigjv2 cord-335279-cfv18qn0 cord-343690-rafvxgx1 cord-336536-ie5ok0lz cord-338436-0z828org cord-342130-eo4le4v3 cord-341138-mxjsp3cm cord-339752-o6atz33c cord-341968-uc8i9h0m cord-342739-iy9vjpuh cord-338973-73a7uvyz cord-346836-6jyv0q5e cord-323585-iv2dcpqj cord-345651-admlzeu4 cord-345472-qrddwebe cord-347053-m5m4zgfy cord-349560-8n65rgfz cord-349011-kxhpdvri cord-347362-e4paw26n cord-348968-0yoq0geu cord-338811-2bi2edcw cord-349117-xfir3m5p cord-351228-hpo8bboi cord-351489-tzmev77c cord-342923-prgorr3d cord-351365-dc9t3vh3 cord-351955-9l4786lb cord-351377-xorj8tnz cord-350964-0jtfc271 cord-352007-3djwbivp cord-352527-eeyqh9nc cord-351760-698voi9y cord-353365-ujz5nkk3 cord-352619-s2x53grh cord-354738-4rxradwz cord-353609-no3mbg5d cord-354068-4qlk6y7h Creating transaction Updating ent table ===== Reducing parts of speech cord-003453-p2buyrcj cord-001972-1zisomq5 cord-003646-kjkuet78 cord-003516-l1lq8yga cord-002994-1zjrunzc cord-002590-24o2viv3 cord-002691-synm1cyw cord-001831-3aonqyub cord-003407-f5v3hhr8 cord-001887-d6ycc8ci cord-003284-hjx2d5rq cord-000804-0hlj6r10 cord-003334-ion97n4b cord-003130-p2h8p5bm cord-002808-84np9brx 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cord-352527-eeyqh9nc cord-308201-lavcsqov number of items: 243 sum of words: 1,396,537 average size in words: 6,618 average readability score: 47 nouns: virus; cells; infection; protein; viruses; cell; proteins; replication; study; expression; host; coronavirus; type; activity; disease; gene; analysis; mice; response; samples; membrane; results; vaccine; studies; genome; role; influenza; antibodies; cats; data; species; sequence; antibody; sequences; infections; time; bats; strains; responses; control; patients; receptor; genes; detection; acid; levels; activation; assay; number; entry verbs: used; shown; infect; induced; include; binds; associated; identified; detected; based; containing; suggests; indicate; found; inhibit; increases; observed; following; compared; mediated; expressed; report; described; determined; performed; causes; required; demonstrate; resulting; isolated; provides; targeting; tested; involved; reduce; leading; known; reveals; treat; occurring; developed; generate; obtained; neutralizing; produced; encoding; signaling; analyzed; activating; collected adjectives: viral; human; respiratory; different; immune; specific; antiviral; high; anti; positive; infectious; cellular; clinical; non; like; infected; recombinant; feline; new; important; severe; similar; novel; several; dependent; acute; significant; higher; structural; negative; molecular; low; first; porcine; multiple; many; single; genetic; innate; small; large; potential; present; recent; primary; early; lower; available; previous; major adverbs: also; however; well; respectively; previously; therefore; highly; significantly; recently; moreover; furthermore; interestingly; even; still; first; together; subsequently; directly; currently; approximately; additionally; often; especially; similarly; specifically; finally; mainly; newly; less; prior; likely; closely; potentially; usually; indeed; briefly; least; alone; yet; encephalitis; particularly; relatively; rather; efficiently; generally; commonly; far; later; strongly; almost pronouns: we; it; their; its; our; i; they; them; us; his; itself; her; he; one; themselves; she; nsp15; my; your; imagej; ifitm3; m19fc; impdh2; eef1a; you; p28; d509; isg15-/-bmdm; iigp1; himself; hifnα; egfp; z004; s386; rad5; mrnas; isgf3; igg1; icam-5; him; hexim1; ecovs; a129; ™; α1,2-mannosidases; y2h; wupyv; the~5-fold; sunset; rig- proper nouns: RNA; SARS; C; IFN; CoV; PCR; MERS; USA; CoV-2; Figure; PEDV; IBV; Virus; T; ZIKV; RT; N; IRF3; HIV-1; Table; NP; China; ER; S1; RSV; HA; Ebola; EBOV; HCV; S; II; Coronavirus; IAV; M; A; PRRSV; GFP; Vero; PBS; East; •; B; GP; Influenza; Middle; Human; HCoV; FCoV; MARV; TGEV keywords: virus; rna; sars; cell; ifn; mers; infection; protein; dna; bat; pcr; pedv; ibv; ebola; zikv; ebov; covid-19; respiratory; iav; hiv-1; gfp; cat; usa; prrsv; lasv; human; hev; cov-2; zika; viral; vero; vaccine; tgev; rsv; replication; oc43; hcv; feline; east; sequence; nl63; marv; irf3; influenza; fever; elisa; china; west; vsv; tick one topic; one dimension: virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499821/ titles(s): Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa three topics; one dimension: cells; virus; virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411613/, https://doi.org/10.3390/v12090942, https://doi.org/10.3390/v11050471 titles(s): Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression | Optimization Rules for SARS-CoV-2 M(pro) Antivirals: Ensemble Docking and Exploration of the Coronavirus Protease Active Site | Exploiting the Legacy of the Arbovirus Hunters five topics; three dimensions: cells virus viral; virus viruses cats; virus vaccine infection; cells virus protein; virus cov infection file(s): https://doi.org/10.3390/v12060682, https://doi.org/10.3390/v11050471, https://doi.org/10.3390/v12090942, https://doi.org/10.3390/v11080735, https://doi.org/10.3390/v12020194 titles(s): Role of the Guanine Nucleotide Exchange Factor GBF1 in the Replication of RNA Viruses | Exploiting the Legacy of the Arbovirus Hunters | Optimization Rules for SARS-CoV-2 M(pro) Antivirals: Ensemble Docking and Exploration of the Coronavirus Protease Active Site | Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells | Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections Type: cord title: journal-viruses-cord date: 2021-05-30 time: 16:05 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: facet_journal:"Viruses" ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-309571-a0xu1d56 author: Aboughdir, Maryam title: Prognostic Value of Cardiovascular Biomarkers in COVID-19: A Review date: 2020-05-11 words: 5690.0 sentences: 288.0 pages: flesch: 47.0 cache: ./cache/cord-309571-a0xu1d56.txt txt: ./txt/cord-309571-a0xu1d56.txt summary: With intensive care units operating at maximum capacity and such staggering mortality rates reported, it is imperative during this time-sensitive COVID-19 outbreak to identify patients with an increased risk of adverse outcomes and/or myocardial injury. found that myocardial injury, defined by raised serum cardiac troponin I (cTnI) levels, in COVID-19 patients was associated with over 50% mortality rate [12] . In the study by Wang et al., 36 out of 138 (26.1%) COVID-19 patients were admitted to the ICU with severe symptoms, all of whom had significantly elevated serum cTnI and CK-MB levels (p = 0.004 and p < 0.001, respectively) compared to non-ICU patients [11] . cTnI provides remarkable prognostic value for patients at increased risk of worsening outcomes and in-hospital mortality, though studies have also shown the association of raised CK-MB and BNP levels with more severe symptoms of COVID-19. abstract: In early December 2019, the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, China. As of May 10th, 2020, a total of over 4 million COVID-19 cases and 280,000 deaths have been reported globally, reflecting the raised infectivity and severity of this virus. Amongst hospitalised COVID-19 patients, there is a high prevalence of established cardiovascular disease (CVD). There is evidence showing that COVID-19 may exacerbate cardiovascular risk factors and preexisting CVD or may lead to cardiovascular complications. With intensive care units operating at maximum capacity and such staggering mortality rates reported, it is imperative during this time-sensitive COVID-19 outbreak to identify patients with an increased risk of adverse outcomes and/or myocardial injury. Preliminary findings from COVID-19 studies have shown the association of biomarkers of acute cardiac injury and coagulation with worse prognosis. While these biomarkers are recognised for CVD, there is emerging prospect that they may aid prognosis in COVID-19, especially in patients with cardiovascular comorbidities or risk factors that predispose to worse outcomes. Consequently, the aim of this review is to identify cardiovascular prognostic factors associated with morbidity and mortality in COVID-19 and to highlight considerations for incorporating laboratory testing of biomarkers of cardiovascular performance in COVID-19 to optimise outcomes. url: https://doi.org/10.3390/v12050527 doi: 10.3390/v12050527 id: cord-289757-jtvpfsiu author: Abrams, Anna title: The Prevalence and Significance of HTLV-I/II Seroindeterminate Western Blot Patterns date: 2011-08-02 words: 3490.0 sentences: 161.0 pages: flesch: 42.0 cache: ./cache/cord-289757-jtvpfsiu.txt txt: ./txt/cord-289757-jtvpfsiu.txt summary: Interestingly, when DNA isolated from peripheral blood mononuclear cells (PBMC) of these HTLV-I/II seroindeterminate individuals is amplified using polymerase chain reaction (PCR) assays, typically no HTLV-I or HTLV-II virus is detected (however, recent reports from Iran, Argentina, and Brazil have challenged this finding) [17] . Enhanced specificity of truncated transmembrane protein for serologic confirmation of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections by western blot (immunoblot) assay containing recombinant envelope glycoproteins Serological, epidemiological, and molecular differences between human T-cell lymphotropic virus Type 1 (HTLV-1)-seropositive healthy carriers and persons with HTLV-I Gag indeterminate Western blot patterns from the Caribbean Molecular analysis of human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) seroindeterminate blood donors from Northeast Iran: Evidence of proviral tax, env, and gag sequences abstract: Human T-lymphotropic virus type I (HTLV-I) infects an estimated 15–20 million persons worldwide. A number of diseases have been associated with the virus including adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I uveitis, and HTLV-I-associated infective dermatitis. Once it was shown that there is an increased risk for developing HAM/TSP associated with blood transfusion, screening for HTLV-1 among blood banks was implemented in Japan, United States, France, and the Netherlands. This process includes detection by an enzyme immunoassay (EIA) followed by a confirmatory Western blot (WB) in which recombinant proteins specific for HTLV-I Env glycoproteins are incorporated into WB strips. HTLV-I seropositive results are defined by the presence of antibodies against either gp46 or gp62/68 (both Env protein bands) and either p19, p24, or p53 (one of the gag bands). HTLV-II seropositivity is confirmed by the presence of rgp46-II. However, numerous cases have been documented in which serum samples are reactive by EIA, but an incomplete banding pattern is displayed by subsequent confirmatory WB. Although the significance of these HTLV-I/II seroindeterminates is unclear, it may suggest a much higher incidence of exposure to HTLV-I/II than previously estimated. url: https://doi.org/10.3390/v3081320 doi: 10.3390/v3081320 id: cord-292050-x3isowrt author: Ackerman, Emily E. title: Network Controllability-Based Prioritization of Candidates for SARS-CoV-2 Drug Repositioning date: 2020-09-26 words: 6948.0 sentences: 384.0 pages: flesch: 44.0 cache: ./cache/cord-292050-x3isowrt.txt txt: ./txt/cord-292050-x3isowrt.txt summary: Based on network topology and controllability, 16 proteins involved in translation, cellular transport, cellular stress, and host immune response are predicted as regulators of the SARS-CoV-2 infected cell. Screenings of experimentally verified SARS-CoV-2 interacting host proteins [7] have elucidated key infection mechanisms which, when compared to drug databases, have predicted a range of possible targets for repurposing. To assess whether the robust controllability classifications of the driver and virus interacting proteins are a result of the network''s connectivity structure, a randomization analysis was performed as developed in previous work [11] . The eight critical virus interacting proteins of the HIN become intermittent in the VIN, losing some control over infected network regulation. The eight critical virus interacting proteins of the HIN become intermittent in the VIN, losing some control over infected network regulation. abstract: In a short time, the COVID-19 pandemic has left the world with over 25 million cases and staggering death tolls that are still rising. Treatments for SARS-CoV-2 infection are desperately needed as there are currently no approved drug therapies. With limited knowledge of viral mechanisms, a network controllability method of prioritizing existing drugs for repurposing efforts is optimal for quickly moving through the drug approval pipeline using limited, available, virus-specific data. Based on network topology and controllability, 16 proteins involved in translation, cellular transport, cellular stress, and host immune response are predicted as regulators of the SARS-CoV-2 infected cell. Of the 16, eight are prioritized as possible drug targets where two, PVR and SCARB1, are previously unexplored. Known compounds targeting these genes are suggested for viral inhibition study. Prioritized proteins in agreement with previous analysis and viral inhibition studies verify the ability of network controllability to predict biologically relevant candidates. url: https://www.ncbi.nlm.nih.gov/pubmed/32993136/ doi: 10.3390/v12101087 id: cord-309239-6lso1w0o author: Adney, Danielle R. title: Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding date: 2016-08-19 words: 2989.0 sentences: 149.0 pages: flesch: 50.0 cache: ./cache/cord-309239-6lso1w0o.txt txt: ./txt/cord-309239-6lso1w0o.txt summary: The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen first described from Saudi Arabia in 2012 [1] that can cause severe respiratory disease and death in roughly 36% of infected humans [2] . There is considerable field and experimental evidence that dromedary camels serve as an important reservoir host involved in transmission to humans [3] [4] [5] [6] [7] [8] , but whether other livestock such as goats, sheep, and horses play a role in transmission has only been assessed indirectly. The objective of this study was to determine if goats, sheep, and horses can be infected with MERS-CoV and assess their potential importance in viral transmission. Sheep, goat kids and horses were each inoculated intranasally with 1.4 × 10 6 to 1.9 × 10 6 plaque-forming units (PFU) of a low passage human isolate of MERS-CoV (strain HCoV-EMC/2012) propagated in Vero E6 cells as described previously [11] . abstract: The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 and can cause severe disease in infected humans. Dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. Data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. In order to understand if these animals could be infected, we challenged young goats and horses and adult sheep with MERS-CoV by intranasal inoculation. Minimal or no virus shedding was detected in all of the animals. During the four weeks following inoculation, neutralizing antibodies were detected in the young goats, but not in sheep or horses. url: https://www.ncbi.nlm.nih.gov/pubmed/27548203/ doi: 10.3390/v8080230 id: cord-267733-fuz8r3vj author: Al Ali, Sally title: Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors date: 2016-05-21 words: 7966.0 sentences: 392.0 pages: flesch: 41.0 cache: ./cache/cord-267733-fuz8r3vj.txt txt: ./txt/cord-267733-fuz8r3vj.txt summary: This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost in comparison to other production systems [21, 24] . This reporter gene system has been widely used in transgenic plants, and it has also been successfully used in mammalian cells for VACV recombinant virus selection [54] . Reporter-gene assays have helped the pox virologists in basic research, for example for the study of the location, structure and function of many VACV proteins during the infection cycle and their interaction with proteins of the host cell [44, 70] . The main limitation of using VACV as a vector is the short-term gene expression, since it is a lytic virus killing the infected cells. Insertion sites for recombinant vaccinia virus construction: Effects on expression of a foreign protein abstract: Vaccinia virus (VACV) is one of the most extensively-studied viruses of the Poxviridae family. It is easy to genetically modify, so it has become a key tool for many applications. In this context, reporter genes facilitate the study of the role of foreign genes introduced into the genome of VACV. In this review, we describe the type of reporter genes that have been used to generate reporter-expressing VACV and the applications of the recombinant viruses obtained. Reporter-expressing VACV are currently employed in basic and immunology research, in the development of vaccines and cancer treatment. url: https://doi.org/10.3390/v8050134 doi: 10.3390/v8050134 id: cord-290127-51ljxy72 author: Al-Kassmy, Jawad title: Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand? date: 2020-08-07 words: 7368.0 sentences: 369.0 pages: flesch: 46.0 cache: ./cache/cord-290127-51ljxy72.txt txt: ./txt/cord-290127-51ljxy72.txt summary: While the S protein is by far the most studied region for vaccine designs, in silico analyses of potential immunogenic epitopes in the SARS-CoV-2 have suggested several domains within the N, M, and E protein as well as the non-structural proteins primarily focusing on T cell responses [21] [22] [23] [24] [25] . Looking at SARS, several vaccines using different viral vectors or DNA were able to induce high levels of neutralizing antibodies using the full-length S protein, which, in some models, provided protection against challenge [36] [37] [38] [39] [40] . When comparing different vaccine platforms, one study looked at the inactivated vaccines and adenovirus vectors expressing the S protein, or the N protein of SARS reported increased protection when utilizing the whole inactivated virus. A Phase I/II, randomized, placebo-controlled, observer-blind, dose-finding trial in the United States (NCT04368728/NCT04380701) is evaluating the safety, tolerability, immunogenicity, and efficacy of four SARS-CoV-2 RNA vaccine candidates (BNT162a1, BNT162b1, BNT162b2, and BNT162c2) in healthy adults between 18 and 85 years old. abstract: Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette–Guérin (BCG) vaccines, DNA and RNA-based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32784685/ doi: 10.3390/v12080861 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-274569-jh0dyyz7 author: Alenquer, Marta title: Exosome Biogenesis, Regulation, and Function in Viral Infection date: 2015-09-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Exosomes are extracellular vesicles released upon fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs) during the process of MVB formation. Exosomes were shown to contain selectively sorted functional proteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in the physiology of the healthy and diseased organism. Challenges in the field include the identification of mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles and the understanding of the underlying processes directing MVBs for degradation or fusion with the plasma membrane. The investigation into the formation and roles of exosomes in viral infection is in its early years. Although still controversial, exosomes can, in principle, incorporate any functional factor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation. This review initially focuses on the composition and biogenesis of exosomes. It then explores the regulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system, which is tightly regulated and able to respond to several stimuli that lead to alterations in the composition of its sub-compartments. We discuss the current knowledge of how these changes affect exosomal release. We then summarize how different viruses exploit specific proteins of endocytic sub-compartments and speculate that it could interfere with exosome function, although no direct link between viral usage of the endocytic system and exosome release has yet been reported. Many recent reports have ascribed functions to exosomes released from cells infected with a variety of animal viruses, including viral spread, host immunity, and manipulation of the microenvironment, which are discussed. Given the ever-growing roles and importance of exosomes in viral infections, understanding what regulates their composition and levels, and defining their functions will ultimately provide additional insights into the virulence and persistence of infections. url: https://doi.org/10.3390/v7092862 doi: 10.3390/v7092862 id: cord-281552-zfjy3m3i author: Alsaadi, Entedar A. J. title: Identification of a Membrane Binding Peptide in the Envelope Protein of MHV Coronavirus date: 2020-09-22 words: 4781.0 sentences: 205.0 pages: flesch: 49.0 cache: ./cache/cord-281552-zfjy3m3i.txt txt: ./txt/cord-281552-zfjy3m3i.txt summary: Here, we test E-derived peptides for membrane binding activity in vitro and confirm those identified as positive in the context of the full length protein expressed in two different cell types. Relative densitometry of the HSP and LSP bands revealed significant differences among the mutants with regard to their localisation to the different membrane fractions of E expressing insect cells ( Figure 5B ) and confirmed a role for the amphipathic MHV CoV E 50-64 peptide in membrane interaction. An amphipathic helix, EPTM, detected in the post-TM region of E, was suggested by bioinformatics analysis and assessed for direct membrane interaction in vitro by binding to GUVs. For comparison, the predicted E protein TM domain, ETM, and an established membrane active peptide from the influenza M2 protein were also included. Following expression of the complete E protein with mutations in the same identified peptide, altered membrane binding in two distinct cell types, mammalian and insect, was apparent. abstract: Coronaviruses (CoVs) are enveloped, positive sense, single strand RNA viruses that cause respiratory, intestinal and neurological diseases in mammals and birds. Following replication, CoVs assemble on intracellular membranes including the endoplasmic reticulum Golgi intermediate compartment (ERGIC) where the envelope protein (E) functions in virus assembly and release. In consequence, E potentially contains membrane-modifying peptides. To search for such peptides, the E coding sequence of Mouse Hepatitis Virus (MHV) was inspected for its amino acid conservation, proximity to the membrane and/or predicted amphipathic helices. Peptides identified in silico were synthesized and tested for membrane-modifying activity in the presence of giant unilamellar vesicles (GUVs) consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), sphingomyelin and cholesterol. To confirm the presence of membrane binding peptides identified in the context of a full-length E protein, the wild type and a number of mutants in the putative membrane binding peptide were expressed in Lenti-X-293T mammalian and insect cells, and the distribution of E antigen within the expressing cell was assessed. Our data identify a role for the post-transmembrane region of MHV E in membrane binding. url: https://www.ncbi.nlm.nih.gov/pubmed/32971895/ doi: 10.3390/v12091054 id: cord-272010-kc0gi3cj author: Anand, Sai Priya title: Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins date: 2020-09-29 words: 3661.0 sentences: 216.0 pages: flesch: 56.0 cache: ./cache/cord-272010-kc0gi3cj.txt txt: ./txt/cord-272010-kc0gi3cj.txt summary: The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. One potential therapeutic target receiving significant attention is the interaction between the SARS-CoV-2 spike (S) glycoprotein and its receptor, human angiotensin-converting enzyme 2 (ACE2). To better understand the interactions between membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins with their receptor, human ACE2, we sought to determine the cooperativity of ACE2 within the respective trimers. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2 abstract: Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is responsible for the current global coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. A better understanding of the spike/ACE2 interaction is still required to design anti-SARS-CoV-2 therapeutics. Here, we investigated the degree of cooperativity of ACE2 within both the SARS-CoV-2 and the closely related SARS-CoV-1 membrane-bound S glycoproteins. We show that there exist differential inter-protomer conformational transitions between both spike trimers. Interestingly, the SARS-CoV-2 spike exhibits a positive cooperativity for monomeric soluble ACE2 binding when compared to the SARS-CoV-1 spike, which might have more structural restraints. Our findings can be of importance in the development of therapeutics that block the spike/ACE2 interaction. url: https://doi.org/10.3390/v12101104 doi: 10.3390/v12101104 id: cord-334855-s0ci3r8w author: Andersen, Petter I. title: Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine date: 2019-10-18 words: 4274.0 sentences: 272.0 pages: flesch: 48.0 cache: ./cache/cord-334855-s0ci3r8w.txt txt: ./txt/cord-334855-s0ci3r8w.txt summary: Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. The expected response of the emetine-obatoclax drug combination on the viability of FLUAV-and mock-infected RPE cells was calculated using Bliss reference model [29] . After the initial screening, we identified four compounds (obatoclax, emetine, niclosamide and ganciclovir) that at none-cytotoxic concentrations rescued cells from virus-mediated death (Figure 2A) . Table S1 : Compounds, their suppliers and catalogue numbers; Table S2 : Developmental status of broad-spectrum antivirals used in the study; Table S3 : Human viruses and associated diseases; Figure S1 : The expected response of the emetine-obatoclax drug combination on the viability of FLUAV-and mock-infected RPE cells, as measured with the CTG assay using the Bliss reference model; Figure S2 abstract: Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests. url: https://doi.org/10.3390/v11100964 doi: 10.3390/v11100964 id: cord-324617-yok7mh70 author: Andreata-Santos, Robert title: Transcutaneous Administration of Dengue Vaccines date: 2020-05-06 words: 6337.0 sentences: 283.0 pages: flesch: 44.0 cache: ./cache/cord-324617-yok7mh70.txt txt: ./txt/cord-324617-yok7mh70.txt summary: Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. The addition of LT1 to the vaccines significantly enhanced the DENV2-specific serum IgG responses elicited in the mice immunized via the TC or ID route, with the maximal values reached two weeks after the third vaccine dose ( Figure 1A ,B). The ID-immunized mice showed significant differences in DENV2-specific serum IgG responses in the presence of LT1, particularly in the group immunized with 50 µg of the tested antigen ( Figure 1D ). The ID-immunized mice showed significant differences in DENV2-specific serum IgG responses in the presence of LT1, particularly in the group immunized with 50 µg of the tested antigen ( Figure 1D ). abstract: In the present study, we evaluated the immunological responses induced by dengue vaccines under experimental conditions after delivery via a transcutaneous (TC) route. Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. As a control for the parenteral administration route, other mouse groups were immunized with the same vaccine formulation via the intradermic (ID) route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. Notably, the vaccine delivered through the TC route induced lower serum antibody (IgG) responses with regard to ID-immunized mice, particularly after the third dose. The protective immunity elicited in TC-immunized mice was attributed to different antigen-specific antibody properties, such as epitope specificity and IgG subclass responses, and cellular immune responses, as determined by cytokine secretion profiles. Altogether, the results of the present study demonstrate the immunogenicity and protective properties of a dengue vaccine delivered through the TC route and offer perspectives for future clinical applications. url: https://doi.org/10.3390/v12050514 doi: 10.3390/v12050514 id: cord-003861-qeao4ghg author: Aris-Brosou, Stéphane title: Viral Long-Term Evolutionary Strategies Favor Stability over Proliferation date: 2019-07-24 words: 4513.0 sentences: 209.0 pages: flesch: 49.0 cache: ./cache/cord-003861-qeao4ghg.txt txt: ./txt/cord-003861-qeao4ghg.txt summary: To understand how these two processes affect the long-term evolution of viruses infecting humans, we comprehensively analyzed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus types and which functions show evidence for episodic diversifying selection and correlated evolution. To better understand the role of correlated evolution and positive selection in the evolutionary dynamics of viruses infecting humans, we constructed a nearly exhaustive viral data set spanning all dsDNA, dsRNA, ssRNA, and ssDNA viruses deposited in GenBank (as of August 2017), and conducted an extensive survey of correlated evolution and diversifying selection in these viruses, asking more specifically about the prevalence of these two processes in each viral type, independently or jointly, with the specific hypothesis that the genes affected by both processes encode functions that are most critical to each viral life cycle. abstract: Viruses are known to have some of the highest and most diverse mutation rates found in any biological replicator, with single-stranded (ss) RNA viruses evolving the fastest, and double-stranded (ds) DNA viruses having rates approaching those of bacteria. As mutation rates are tightly and negatively correlated with genome size, selection is a clear driver of viral evolution. However, the role of intragenomic interactions as drivers of viral evolution is still unclear. To understand how these two processes affect the long-term evolution of viruses infecting humans, we comprehensively analyzed ssRNA, ssDNA, dsRNA, and dsDNA viruses, to find which virus types and which functions show evidence for episodic diversifying selection and correlated evolution. We show that selection mostly affects single stranded viruses, that correlated evolution is more prevalent in DNA viruses, and that both processes, taken independently, mostly affect viral replication. However, the genes that are jointly affected by both processes are involved in key aspects of their life cycle, favoring viral stability over proliferation. We further show that both evolutionary processes are intimately linked at the amino acid level, which suggests that it is the joint action of selection and correlated evolution, and not just selection, that shapes the evolutionary trajectories of viruses—and possibly of their epidemiological potential. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722887/ doi: 10.3390/v11080677 id: cord-004508-ok3px98z author: Armando, Federico title: Oxidative Stress in Canine Histiocytic Sarcoma Cells Induced by an Infection with Canine Distemper Virus Led to a Dysregulation of HIF-1α Downstream Pathway Resulting in a Reduced Expression of VEGF-B In Vitro date: 2020-02-11 words: 8265.0 sentences: 382.0 pages: flesch: 38.0 cache: ./cache/cord-004508-ok3px98z.txt txt: ./txt/cord-004508-ok3px98z.txt summary: Based on these findings, the aim of the present study was to investigate the impact of a persistent CDV-infection on oxidative stress mediated changes in the expression of hypoxia-inducible factor (HIF)-1α and its angiogenic downstream pathway in DH82 cells in vitro. In summary, these results suggest a reduced activation of the HIF-1α angiogenic downstream pathway in DH82Ond pi cells in vitro, most likely due to an excessive, unusually localized, and non-functional expression of HIF-1α triggered by a CDV-induced increased oxidative stress. In a hypothesis-driven approach, an online available microarray data set of quadruplicates of non-infected DH82 and DH82Ond pi cells (ArrayExpress; http://www.ebi.ac.uk/arrayexpress; accession number E-MTAB-3942 [11, 44] ) was investigated for differentially expressed genes related to ROS production and scavenging, ER-stress and HIF-1α pathway, with a special focus on the angiogenic downstream targets of the latter. abstract: Histiocytic sarcomas represent malignant tumors which require new treatment strategies. Canine distemper virus (CDV) is a promising candidate due to its oncolytic features reported in a canine histiocytic sarcoma cell line (DH82 cells). Interestingly, the underlying mechanism might include a dysregulation of angiogenesis. Based on these findings, the aim of the present study was to investigate the impact of a persistent CDV-infection on oxidative stress mediated changes in the expression of hypoxia-inducible factor (HIF)-1α and its angiogenic downstream pathway in DH82 cells in vitro. Microarray data analysis, immunofluorescence for 8-hydroxyguanosine, superoxide dismutase 2 and catalase, and flow cytometry for oxidative burst displayed an increased oxidative stress in persistently CDV-infected DH82 cells (DH82Ond pi) compared to controls. The HIF-1α expression in DH82Ond pi increased, as demonstrated by Western blot, and showed an unexpected, often sub-membranous distribution, as shown by immunofluorescence and immunoelectron microscopy. Furthermore, microarray data analysis and immunofluorescence confirmed a reduced expression of VEGF-B in DH82Ond pi compared to controls. In summary, these results suggest a reduced activation of the HIF-1α angiogenic downstream pathway in DH82Ond pi cells in vitro, most likely due to an excessive, unusually localized, and non-functional expression of HIF-1α triggered by a CDV-induced increased oxidative stress. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077254/ doi: 10.3390/v12020200 id: cord-301810-vtgdqart author: Aston, Emily J. title: Effect of Pullet Vaccination on Development and Longevity of Immunity date: 2019-02-02 words: 7115.0 sentences: 321.0 pages: flesch: 45.0 cache: ./cache/cord-301810-vtgdqart.txt txt: ./txt/cord-301810-vtgdqart.txt summary: Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). At 5 days following challenge with IBV GA98, vaccinated/challenged birds had significantly lower RNA loads compared to positive controls at all collection times and in all tissue samples, with the exception of cecal tonsil at 24 WOA (Table 1 ). ILTV-specific IgG titers in serum collected 5 days post-challenge were significantly higher in vaccinated birds from both challenged and non-challenged groups, compared to the positive and negative controls ( Figure 6 ). ILTV-specific IgG titers in serum collected 5 days post-challenge were significantly higher in vaccinated birds from both challenged and non-challenged groups, compared to the positive and negative controls ( Figure 6 ). abstract: Avian respiratory disease causes significant economic losses in commercial poultry. Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). Often the interval between vaccinations is only a matter of weeks, yet it is unknown whether the development of immunity and protection against challenge when vaccines are given in short succession occurs in these birds, something known as viral interference. Our objective was to determine whether serially administered, live attenuated vaccines against IBV, NDV, and ILTV influence the development and longevity of immunity and protection against challenge in long-lived birds. Based on a typical pullet vaccination program, specific-pathogen-free white leghorns were administered multiple live attenuated vaccines against IBV, NDV, and ILTV until 16 weeks of age (WOA), after which certain groups were challenged with IBV, NDV, or ILTV at 20, 24, 28, 32, and 36 WOA. Five days post-challenge, viral load, clinical signs, ciliostasis, tracheal histopathology, and antibody titers in serum and tears were evaluated. We demonstrate that pullets serially administered live attenuated vaccines against IBV, NDV, and ILTV were protected against homologous challenge with IBV, NDV, or ILTV for at least 36 weeks, and conclude that the interval between vaccinations used in this study (at least 2 weeks) did not interfere with protection. This information is important because it shows that a typical pullet vaccination program consisting of serially administered live attenuated vaccines against multiple respiratory pathogens can result in the development of protective immunity against each disease agent. url: https://doi.org/10.3390/v11020135 doi: 10.3390/v11020135 id: cord-264526-bxpzo2xu author: Aydin, Malik title: House Dust Mite Exposure Causes Increased Susceptibility of Nasal Epithelial Cells to Adenovirus Infection date: 2020-10-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Adenovirus (AdV) infections in the respiratory tract may cause asthma exacerbation and allergic predisposition, and the house dust mite (HDM) may aggravate virus-induced asthma exacerbations. However, the underlying mechanisms of whether and how AdV affects asthmatic patients remains unclear. To address this question, we investigated nasal epithelial cells (NAEPCs) derived from a pediatric exacerbation study cohort for experimental analyses. We analyzed twenty-one different green-fluorescent protein- and luciferase-tagged AdV types in submerged 2D and organotypic 3D cell culture models. Transduction experiments revealed robust transduction of AdV type 5 (AdV5) in NAEPCs, which was associated with an increased uptake of AdV5 in the presence of HDM. In healthy and asthmatic NAEPCs exposed to HDM before infection, we observed a time- and dose-dependent increase of AdV5 uptake associated with upregulation of entry receptors for AdV5. Furthermore, electron microscopic and histologic analyses of 3D cell cultures revealed an impairment of the respiratory cilia after HDM exposition. This ex vivo pilot study shows the impact of AdV infection and HDM exposition in a primary cell culture model for asthma. url: https://doi.org/10.3390/v12101151 doi: 10.3390/v12101151 id: cord-003586-afnto2tz author: Baillet, Nicolas title: Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses date: 2019-03-23 words: 7588.0 sentences: 380.0 pages: flesch: 51.0 cache: ./cache/cord-003586-afnto2tz.txt txt: ./txt/cord-003586-afnto2tz.txt summary: We identified host cellular proteins that interact with Z proteins of both viruses by using a high throughput yeast two-hybrid (HT-Y2H) screening protocol in which AH109 yeast cells were transformed with a Y2H vector encoding the Z protein of LASV or MOPV fused to the GAL4-BD domain (viral bait). Y2H screens allowed us to identify, among others, two known autophagy adaptors, namely NDP52 and TAX1BP1, which have been shown to interact with the Z protein of MOPV, but not LASV (Table 1) . Overall, these results suggest that NDP52 and TAX1BP1 are not involved in the production of infectious virus for either MOPV or LASV in HeLa cells. These results were unexpected and suggest that autophagy adaptors could play a role during LASV or MOPV infection that does not affect the viral fitness in the cell lines we used. abstract: Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic mechanisms that occur during the course of pathogenic arenavirus infection. We used a yeast two-hybrid approach to identify cell partners of MOPV and LASV Z matrix protein in which two autophagy adaptors were identified, NDP52 and TAX1BP1. Autophagy has emerged as an important cellular defense mechanism against viral infections but its role during arenavirus infection has not been shown. Here, we demonstrate that autophagy is transiently induced by MOPV, but not LASV, in infected cells two days after infection. Impairment of the early steps of autophagy significantly decreased the production of MOPV and LASV infectious particles, whereas a blockade of the degradative steps impaired only MOPV infectious particle production. Our study provides insights into the role played by autophagy during MOPV and LASV infection and suggests that this process could partially explain their different pathogenicity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466445/ doi: 10.3390/v11030293 id: cord-262434-q4tk96tq author: Baker, Kate S. title: Poxviruses in Bats … so What? date: 2014-04-03 words: 3331.0 sentences: 175.0 pages: flesch: 42.0 cache: ./cache/cord-262434-q4tk96tq.txt txt: ./txt/cord-262434-q4tk96tq.txt summary: Finally, we speculate on the possible consequences and potential research avenues opened following this marrying of a pathogen of great historical and contemporary importance with an ancient host that has an apparently peculiar relationship with viruses; a fascinating and likely fruitful meeting whose study will be facilitated by recent technological advances and a heightened interest in bat virology. Similarly, testing the in vitro host range of isolated viruses such as Eptesipox virus would help inform whether human and further animal cell lines are permissive for infection (i.e., that they contain the necessary host factors to support infection and do not contain antiviral components that restrict infection). Further field (in situ), in vitro and in silico studies could elucidate the possible coevolution, cross species infections and mechanisms of host range restriction of bat poxviruses, the implications of which are relevant for bat ecologists, virologists and emerging infectious disease specialists (including those with a specific interest in bats) alike. abstract: Poxviruses are important pathogens of man and numerous domestic and wild animal species. Cross species (including zoonotic) poxvirus infections can have drastic consequences for the recipient host. Bats are a diverse order of mammals known to carry lethal viral zoonoses such as Rabies, Hendra, Nipah, and SARS. Consequent targeted research is revealing bats to be infected with a rich diversity of novel viruses. Poxviruses were recently identified in bats and the settings in which they were found were dramatically different. Here, we review the natural history of poxviruses in bats and highlight the relationship of the viruses to each other and their context in the Poxviridae family. In addition to considering the zoonotic potential of these viruses, we reflect on the broader implications of these findings. Specifically, the potential to explore and exploit this newfound relationship to study coevolution and cross species transmission together with fundamental aspects of poxvirus host tropism as well as bat virology and immunology. url: https://doi.org/10.3390/v6041564 doi: 10.3390/v6041564 id: cord-257052-cik2wmlk author: Ban, Junsu title: Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling date: 2018-12-14 words: 3885.0 sentences: 215.0 pages: flesch: 43.0 cache: ./cache/cord-257052-cik2wmlk.txt txt: ./txt/cord-257052-cik2wmlk.txt summary: title: Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling. Ectopically expressed NS1 inhibited interferon-β promoter activity that was induced by RIG-IN as determined by the luciferase assays in HEK293T cells, confirming that NS1 itself is capable of inhibiting RIG-I-mediated antiviral signaling ( Figure 1A ). Ectopically expressed NS1 inhibited interferon-β promoter activity that was induced by RIG-IN as determined by the luciferase assays in HEK293T cells, confirming that NS1 itself is capable of inhibiting RIG-I-mediated antiviral signaling ( Figure 1A ). These results suggest that RSV NS1 expression diminishes the interaction between RIG-I and MAVS by interfering with TRIM25-mediated RIG-I ubiquitination. These results indicate that inhibition of TRIM25-mediated RIG-I ubiquitination by NS1 contributes to the suppression of RIG-I signaling, at least in part. abstract: Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease. Retinoic acid-inducible gene-I (RIG-I) serves as an innate immune sensor and triggers antiviral responses upon recognizing viral infections including RSV. Since tripartite motif-containing protein 25 (TRIM25)-mediated K63-polyubiquitination is crucial for RIG-I activation, several viruses target initial RIG-I activation through ubiquitination. RSV NS1 and NS2 have been shown to interfere with RIG-I-mediated antiviral signaling. In this study, we explored the possibility that NS1 suppresses RIG-I-mediated antiviral signaling by targeting TRIM25. Ubiquitination of ectopically expressed RIG-I-2Cards domain was decreased by RSV infection, indicating that RSV possesses ability to inhibit TRIM25-mediated RIG-I ubiquitination. Similarly, ectopic expression of NS1 sufficiently suppressed TRIM25-mediated RIG-I ubiquitination. Furthermore, interaction between NS1 and TRIM25 was detected by a co-immunoprecipitation assay. Further biochemical assays showed that the SPRY domain of TRIM25, which is responsible for interaction with RIG-I, interacted sufficiently with NS1. Suppression of RIG-I ubiquitination by NS1 resulted in decreased interaction between RIG-I and its downstream molecule, MAVS. The suppressive effect of NS1 on RIG-I signaling could be abrogated by overexpression of TRIM25. Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling. url: https://doi.org/10.3390/v10120716 doi: 10.3390/v10120716 id: cord-295433-olmein3q author: Banerjee, Arinjay title: Bats and Coronaviruses date: 2019-01-09 words: 5655.0 sentences: 298.0 pages: flesch: 52.0 cache: ./cache/cord-295433-olmein3q.txt txt: ./txt/cord-295433-olmein3q.txt summary: Initial studies investigating animal sources of the virus from "wet markets" in the Guangdong province of China suggested that Himalayan palm civets and raccoon dogs were the most likely hosts responsible for human transmission [22] ; however, the role of bats as the original animal reservoir hosts of SARS-CoV was speculated as similar viruses were detected in them [27, 28] . A recent study found that 16 out of 30 camel workers surveyed in Saudi Arabia show evidence of prior MERS-CoV infection via seroconversion and/or virus-specific CD8+ T cell responses without any history of significant respiratory disease. The primary bat species being used to study the bat immune response to virus infections in vitro and in vivo are Pteropus alecto (black flying fox), Rousettus aegyptiacus (Egyptian rousette), and Artibeus jamaicensis (Jamaican fruit bat). Multiple studies with PEDV, SARS-and MERS-CoVs have identified accessory proteins that can effectively inhibit an IFN response in mammalian cells [12] [13] [14] [91] [92] [93] [94] [95] . abstract: Bats are speculated to be reservoirs of several emerging viruses including coronaviruses (CoVs) that cause serious disease in humans and agricultural animals. These include CoVs that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), porcine epidemic diarrhea (PED) and severe acute diarrhea syndrome (SADS). Bats that are naturally infected or experimentally infected do not demonstrate clinical signs of disease. These observations have allowed researchers to speculate that bats are the likely reservoirs or ancestral hosts for several CoVs. In this review, we follow the CoV outbreaks that are speculated to have originated in bats. We review studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease. We speculate about future studies that are critical to identify how bats can harbor multiple strains of CoVs and factors that enable these viruses to “jump” from bats to other mammals. We hope that this review will enable readers to identify gaps in knowledge that currently exist and initiate a dialogue amongst bat researchers to share resources to overcome present limitations. url: https://www.ncbi.nlm.nih.gov/pubmed/30634396/ doi: 10.3390/v11010041 id: cord-289273-zpyz1krq author: Barry, Michele title: Poxvirus Exploitation of the Ubiquitin-Proteasome System date: 2010-10-19 words: 7212.0 sentences: 404.0 pages: flesch: 44.0 cache: ./cache/cord-289273-zpyz1krq.txt txt: ./txt/cord-289273-zpyz1krq.txt summary: Members of the poxvirus family have recently been shown to encode BTB/kelch and ankyrin/F-box proteins that interact with cullin-3 and cullin-1 based ubiquitin ligases, respectively. Recently, cellular BTB domain-containing proteins have been shown to function as substrate-specific adaptors of cullin-3 based ubiquitin ligase to target proteins for ubiquitination [54] [55] [56] [57] . Although the poxviral ankyrin repeat proteins contain no obvious structural domains at their C-termini, many of the proteins display a conserved sequence, which upon closer inspection was shown to resemble the F-box domain that functions in the recruitment of substrates to the cellular SCF (Skp-1, cullin, F-box) ubiquitin ligase complex [82] [83] [84] . The complex consists of cullin-1, which serves as the molecular scaffold, Roc1, a RING finger ubiquitin ligase, Skp1, the linker protein, and one of over 70 known cellular F-box proteins which function in substrate recruitment ( Figure 2D ) [84] [85] [86] . abstract: Ubiquitination plays a critical role in many cellular processes. A growing number of viruses have evolved strategies to exploit the ubiquitin-proteasome system, including members of the Poxviridae family. Members of the poxvirus family have recently been shown to encode BTB/kelch and ankyrin/F-box proteins that interact with cullin-3 and cullin-1 based ubiquitin ligases, respectively. Multiple members of the poxvirus family also encode ubiquitin ligases with intrinsic activity. This review describes the numerous mechanisms that poxviruses employ to manipulate the ubiquitin-proteasome system. url: https://www.ncbi.nlm.nih.gov/pubmed/21994622/ doi: 10.3390/v2102356 id: cord-003453-p2buyrcj author: Batista, Mariana N. title: Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus date: 2019-01-11 words: 4157.0 sentences: 220.0 pages: flesch: 49.0 cache: ./cache/cord-003453-p2buyrcj.txt txt: ./txt/cord-003453-p2buyrcj.txt summary: In this study, we tested the activity of the natural compounds berberine and emodin for their ability to inhibit ZIKV infection. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. The supernatant containing infectious virus particles was incubated for 1 h at different concentrations of each compound (berberine: 20-160 µM and emodin: 0.04-40 µM) and subsequently used to infect Vero E6 cells. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. Vero E6 cells were incubated with berberine or emodin for 1 h at the highest non-toxic concentrations prior to ZIKV infection. abstract: Zika virus (ZIKV) has been associated with serious health conditions, and an intense search to discover different ways to prevent and treat ZIKV infection is underway. Berberine and emodin possess several pharmacological properties and have been shown to be particularly effective against the entry and replication of several viruses. We show that emodin and berberine trigger a virucidal effect on ZIKV. When the virus was exposed to 160 µM of berberine, a reduction of 77.6% in the infectivity was observed; when emodin was used (40 µM), this reduction was approximately 83.3%. Dynamic light scattering data showed that both compounds significantly reduce the hydrodynamic radius of virus particle in solution. We report here that berberine and emodin, two natural compounds, have strong virucidal effect in Zika virus. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356660/ doi: 10.3390/v11010049 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-335567-ssnvr6nj author: Berry, Michael title: Identification of New Respiratory Viruses in the New Millennium date: 2015-03-06 words: 7477.0 sentences: 379.0 pages: flesch: 40.0 cache: ./cache/cord-335567-ssnvr6nj.txt txt: ./txt/cord-335567-ssnvr6nj.txt summary: In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. In recent years six new human respiratory viruses have been reported including human metapneumovirus (hMPV) [16] , bocavirus and four new human coronaviruses including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), HCoV-HKU1 and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children Genetic variability of human coronavirus OC43-, 229E-, and NL63-like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients abstract: The rapid advancement of molecular tools in the past 15 years has allowed for the retrospective discovery of several new respiratory viruses as well as the characterization of novel emergent strains. The inability to characterize the etiological origins of respiratory conditions, particularly in children, led several researchers to pursue the discovery of the underlying etiology of disease. In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Human bocavirus, with its four separate lineages, discovered in 2005, has been linked to acute respiratory tract infections and gastrointestinal complications. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. This review will detail the most current clinical and epidemiological findings to all respiratory viruses discovered since 2001. url: https://doi.org/10.3390/v7030996 doi: 10.3390/v7030996 id: cord-013174-whg64w0w author: Bhatta, Tarka Raj title: Infection Dynamics of Swine Influenza Virus in a Danish Pig Herd Reveals Recurrent Infections with Different Variants of the H1N2 Swine Influenza A Virus Subtype date: 2020-09-10 words: 8213.0 sentences: 427.0 pages: flesch: 59.0 cache: ./cache/cord-013174-whg64w0w.txt txt: ./txt/cord-013174-whg64w0w.txt summary: In addition, next generation sequencing (NGS) was used to identify and characterize the complete genome of swIAV circulating in the herd, and to examine the antigenic variability in the antigenic sites of the virus hemagglutinin (HA) and neuraminidase (NA) proteins. In pigs, circulation of IAV, so-called swine influenza A virus (swIAV), is currently mainly limited to three different subtypes including H1N1, H1N2 and H3N2 [5] [6] [7] . In the phylogenetic analysis, the HA sequences of pig ID 250, obtained at weeks 4 and 8 were located in the same cluster and were~0.5% (9/1701) divergent at the nucleotide level and < 1% (5/566) divergent at the amino acid level. Comparison of amino acid sequences of neuraminidase (NA) antigenic sites of pig ID 380 sampled at week 5 and week 22 from the pig herd. abstract: Influenza A virus (IAV) in swine, so-called swine influenza A virus (swIAV), causes respiratory illness in pigs around the globe. In Danish pig herds, a H1N2 subtype named H1N2dk is one of the main circulating swIAV. In this cohort study, the infection dynamic of swIAV was evaluated in a Danish pig herd by sampling and PCR testing of pigs from two weeks of age until slaughter at 22 weeks of age. In addition, next generation sequencing (NGS) was used to identify and characterize the complete genome of swIAV circulating in the herd, and to examine the antigenic variability in the antigenic sites of the virus hemagglutinin (HA) and neuraminidase (NA) proteins. Overall, 76.6% of the pigs became PCR positive for swIAV during the study, with the highest prevalence at four weeks of age. Detailed analysis of the virus sequences obtained showed that the majority of mutations occurred at antigenic sites in the HA and NA proteins of the virus. At least two different H1N2 variants were found to be circulating in the herd; one H1N2 variant was circulating at the sow and nursery sites, while another H1N2 variant was circulating at the finisher site. Furthermore, it was demonstrated that individual pigs had recurrent swIAV infections with the two different H1N2 variants, but re-infection with the same H1N2 variant was also observed. Better understandings of the epidemiology, genetic and antigenic diversity of swIAV may help to design better health interventions for the prevention and control of swIAV infections in the herds. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551734/ doi: 10.3390/v12091013 id: cord-310734-6v7oru2l author: Bolatti, Elisa M. title: A Preliminary Study of the Virome of the South American Free-Tailed Bats (Tadarida brasiliensis) and Identification of Two Novel Mammalian Viruses date: 2020-04-09 words: 8477.0 sentences: 405.0 pages: flesch: 41.0 cache: ./cache/cord-310734-6v7oru2l.txt txt: ./txt/cord-310734-6v7oru2l.txt summary: By conventional nucleic acid detection techniques and/or bioinformatics approaches, the genomes of two novel viruses were completely covered clustering into the Papillomaviridae (Tadarida brasiliensis papillomavirus type 1, TbraPV1) and Genomoviridae (Tadarida brasiliensis gemykibivirus 1, TbGkyV1) families. Overall, a large number of phage-related sequences were detected (77.3% of viral read pairs and 39.9% of viral contigs), likely representing the most abundant entities infecting bacteria present in the bat digestive system, which exhibited similarity mostly to the families Inoviridae, Siphoviridae, and Myoviridae ( Table 1 ). Several mammalian viral families, supported by the contigs and sequencing reads, have been identified previously in New World [23, 24, 26] and Old World [17, 18, 89] bat species. Table S4 : Read pairs and contigs classified as similar to viruses and not taxonomical assigned to viral families identified in anal and oral swab samples of Tadarida brasiliensis obtained by metagenomics using Illumina technology. abstract: Bats provide important ecosystem services as pollinators, seed dispersers, and/or insect controllers, but they have also been found harboring different viruses with zoonotic potential. Virome studies in bats distributed in Asia, Africa, Europe, and North America have increased dramatically over the past decade, whereas information on viruses infecting South American species is scarce. We explored the virome of Tadarida brasiliensis, an insectivorous New World bat species inhabiting a maternity colony in Rosario (Argentina), by a metagenomic approach. The analysis of five pooled oral/anal swab samples indicated the presence of 43 different taxonomic viral families infecting a wide range of hosts. By conventional nucleic acid detection techniques and/or bioinformatics approaches, the genomes of two novel viruses were completely covered clustering into the Papillomaviridae (Tadarida brasiliensis papillomavirus type 1, TbraPV1) and Genomoviridae (Tadarida brasiliensis gemykibivirus 1, TbGkyV1) families. TbraPV1 is the first papillomavirus type identified in this host and the prototype of a novel genus. TbGkyV1 is the first genomovirus reported in New World bats and constitutes a new species within the genus Gemykibivirus. Our findings extend the knowledge about oral/anal viromes of a South American bat species and contribute to understand the evolution and genetic diversity of the novel characterized viruses. url: https://doi.org/10.3390/v12040422 doi: 10.3390/v12040422 id: cord-262499-68vmdqky author: Bordi, Licia title: Frequency and Duration of SARS-CoV-2 Shedding in Oral Fluid Samples Assessed by a Modified Commercial Rapid Molecular Assay date: 2020-10-20 words: 5037.0 sentences: 311.0 pages: flesch: 56.0 cache: ./cache/cord-262499-68vmdqky.txt txt: ./txt/cord-262499-68vmdqky.txt summary: We evaluated the use of commercial Simplexa™ COVID-19 Direct assay on OF samples from hospitalized COVID-19 patients, for identification of SARS-CoV-2 RNA, duration of viral shedding, and determining the assay specificity and sensitivity on OF samples compared to NPS and BAL samples. The first performance evaluation on clinical specimen was done by testing 41 consecutive OF samples, including 9 samples from SARS-CoV-2-negative patients, with the Simplexa™ COVID-19 Direct assay and comparing results with that obtained using RT-PCR method established by Corman VM. The performance of Simplexa™ COVID-19 Direct assays on clinical specimens was further established by testing in parallel NPS and OF samples for the presence of SARS-CoV-2 RNA. The performance of Simplexa™ COVID-19 Direct assays on clinical specimens was further established by testing in parallel NPS and OF samples for the presence of SARS-CoV-2 RNA. Second, results from testing on paired OF, NPS and BAL samples by Simplexa™ COVID-19 Direct assay showed almost perfect concordance for virus detection, and high correlation of Ct values. abstract: Background: RT-PCR on nasopharyngeal (NPS)/oropharyngeal swabs is the gold standard for diagnosis of SARS-CoV-2 infection and viral load monitoring. Oral fluid (OF) is an alternate clinical sample, easy and safer to collect and could be useful for COVID-19 diagnosis, monitoring viral load and shedding. Methods: Optimal assay conditions and analytical sensitivity were established for the commercial Simplexa™ COVID-19 Direct assay adapted to OF matrix. The assay was used to test 337 OF and NPS specimens collected in parallel from 164 hospitalized patients; 50 bronchoalveolar lavage (BAL) specimens from a subgroup of severe COVID-19 cases were also analysed. Results: Using Simplexa™ COVID-19 Direct on OF matrix, 100% analytical detection down to 1 TCID50/mL (corresponding to 4 × 10(3) copies (cp)/mL) was observed. No crossreaction with other viruses transmitted through the respiratory toute was observed. Parallel testing of 337 OF and NPS samples showed highly concordant results (κ = 0.831; 95 % CI = 0.771–0.891), and high correlation of Ct values (r = 0.921; p < 0.0001). High concordance and elevated correlation was observed also between OF and BAL. Prolonged viral RNA shedding was observed up to 100 days from symptoms onset (DSO), with 32% and 29% positivity observed in OF and NPS samples, respectively, collected between 60 and 100 DSO. Conclusions: Simplexa™ COVID-19 Direct assays on OF have high sensitivity and specificity to detect SARS-CoV-2 RNA and provide an alternative to NPS for diagnosis and monitoring SARS-CoV-2 shedding. url: https://www.ncbi.nlm.nih.gov/pubmed/33092065/ doi: 10.3390/v12101184 id: cord-000804-0hlj6r10 author: Brauburger, Kristina title: Forty-Five Years of Marburg Virus Research date: 2012-10-01 words: 14922.0 sentences: 730.0 pages: flesch: 45.0 cache: ./cache/cord-000804-0hlj6r10.txt txt: ./txt/cord-000804-0hlj6r10.txt summary: While the ectodomain, which is mainly formed by GP 1 , mediates binding to entry factors and receptors [87] [88] [89] [90] [91] [92] [93] [94] [95] , the transmembrane subunit GP 2 contains the fusion peptide and is presumed to mediate fusion of the viral and the cellular membrane based on similarity to EBOV GP 2 both at the amino acid and structural level [96, 97] . The IFN-inducible antiviral protein tetherin was shown to block the release of VP40-induced virus-like MARV and EBOV particles, suggesting that tetherin might act as a restriction factor for filovirus release [102, 103] . After the nucleocapsid is released into the cytoplasm of the infected cell, transcription and replication of the viral RNA genome takes place (Figure 7 ). Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections abstract: In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497034/ doi: 10.3390/v4101878 id: cord-273366-xd84f8ct author: Brownsword, Matthew J. title: Infectious Bronchitis Virus Regulates Cellular Stress Granule Signaling date: 2020-05-14 words: 8910.0 sentences: 520.0 pages: flesch: 47.0 cache: ./cache/cord-273366-xd84f8ct.txt txt: ./txt/cord-273366-xd84f8ct.txt summary: Interestingly, we found that IBV is able to inhibit multiple cellular stress granule signaling pathways, whilst at the same time, IBV replication also results in the induction of seemingly canonical stress granules in a proportion of infected cells. Moreover, IBV infection uncouples translational repression and stress granule formation and both processes are independent of eIF2α phosphorylation. Vero cells were infected with IBV and at the indicated time points, cells were fixed and labelled with anti-dsRNA to detect virus infection and with anti-G3BP1 to detect SG. Following identification of SG in IBV infected cells, the requirement for active virus replication in induction of granules was assessed. At 24 hpi, cells were fixed and labelled with anti-G3BP1 (red) to detect stress granules (SG) and IBV infected cells were detected with an anti-dsRNA antibody (green). Junin virus infection impairs stress-granule formation in Vero cells treated with arsenite via inhibition of eIF2alpha phosphorylation abstract: Viruses must hijack cellular translation machinery to express viral genes. In many cases, this is impeded by cellular stress responses. These stress responses result in the global inhibition of translation and the storage of stalled mRNAs, into RNA-protein aggregates called stress granules. This results in the translational silencing of the majority of mRNAs excluding those beneficial for the cell to resolve the specific stress. For example, the expression of antiviral factors is maintained during viral infection. Here we investigated stress granule regulation by Gammacoronavirus infectious bronchitis virus (IBV), which causes the economically important poultry disease, infectious bronchitis. Interestingly, we found that IBV is able to inhibit multiple cellular stress granule signaling pathways, whilst at the same time, IBV replication also results in the induction of seemingly canonical stress granules in a proportion of infected cells. Moreover, IBV infection uncouples translational repression and stress granule formation and both processes are independent of eIF2α phosphorylation. These results provide novel insights into how IBV modulates cellular translation and antiviral stress signaling. url: https://www.ncbi.nlm.nih.gov/pubmed/32422883/ doi: 10.3390/v12050536 id: cord-253629-5aofwe1w author: Bulow, Uriel title: Acidic pH Triggers Lipid Mixing Mediated by Lassa Virus GP date: 2020-07-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Lassa virus (LASV) is the causative agent of Lassa hemorrhagic fever, a lethal disease endemic to Western Africa. LASV entry is mediated by the viral envelope glycoprotein (GP), a class I membrane fusogen and the sole viral surface antigen. Previous studies have identified components of the LASV entry pathway, including several cellular receptors and the requirement of endosomal acidification for infection. Here, we first demonstrate that incubation at a physiological temperature and pH consistent with the late endosome is sufficient to render pseudovirions, bearing LASV GP, non-infectious. Antibody binding indicates that this loss of infectivity is due to a conformational change in GP. Finally, we developed a single-particle fluorescence assay to directly visualize individual pseudovirions undergoing LASV GP-mediated lipid mixing with a supported planar bilayer. We report that exposure to endosomal pH at a physiologic temperature is sufficient to trigger GP-mediated lipid mixing. Furthermore, while a cellular receptor is not necessary to trigger lipid mixing, the presence of lysosomal-associated membrane protein 1 (LAMP1) increases the kinetics of lipid mixing at an endosomal pH. Furthermore, we find that LAMP1 permits robust lipid mixing under less acidic conditions than in its absence. These findings clarify our understanding of LASV GP-mediated fusion and the role of LAMP1 binding. url: https://www.ncbi.nlm.nih.gov/pubmed/32630688/ doi: 10.3390/v12070716 id: cord-002808-84np9brx author: Campos, Samuel K. title: Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2 date: 2017-12-03 words: 9673.0 sentences: 460.0 pages: flesch: 43.0 cache: ./cache/cord-002808-84np9brx.txt txt: ./txt/cord-002808-84np9brx.txt summary: How does L2, the minor capsid protein from a non-enveloped virus, complexed with the vDNA within the lumen of intracellular vesicular compartments, interact with a variety of cytosolic sorting molecules to direct its own transport to the TGN? Given the requirement for furin in TGN localization of L2/vDNA, it is very likely that cleavage triggers a structural change that enables L2 to insert and protrude into the local membrane via the TMD to recruit cytosolic SNXs and retromer. Regardless of the precise mechanisms of L2 translocation, the minor capsid protein eventually leaves vesicular compartments and is seen along with vDNA within interphase nuclei of infected cells, localized to punctate nuclear foci called promyelocytic leukemia (PML) nuclear domains, also known as PML oncogenic domains (PODS), or ND10 bodies [108] . The L2 minor capsid protein of low-risk human papillomavirus type 11 interacts with host nuclear import receptors and viral DNA Direct binding of retromer to human papillomavirus type 16 minor capsid protein L2 mediates endosome exit during viral infection abstract: Since 2012, our understanding of human papillomavirus (HPV) subcellular trafficking has undergone a drastic paradigm shift. Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA) to the cell nucleus, relying on myriad host cell proteins and processes. The major breakthrough finding from these recent endeavors has been the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA. An overview of current models of HPV entry, subcellular trafficking, and the role of L2 during initial infection is provided below, highlighting unresolved questions and gaps in knowledge. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744145/ doi: 10.3390/v9120370 id: cord-263142-o8qbqxhx author: Cavalcante, Liliane T. F. title: Clinical and Molecular Features of Feline Foamy Virus and Feline Leukemia Virus Co-Infection in Naturally-Infected Cats date: 2018-12-11 words: 9123.0 sentences: 432.0 pages: flesch: 52.0 cache: ./cache/cord-263142-o8qbqxhx.txt txt: ./txt/cord-263142-o8qbqxhx.txt summary: We examined blood and buccal swab specimens of domestic cats in Brazil for detection and quantification of each feline virus to evaluate their potential association with disease and transmissibility in animals with single or multiple retroviral infections. Buccal swab gDNA from 33 nested PCR-negative animals identified seven qPCR positive cats with a median pVL of −0.7 log10 copies/cell (201,363 copies/10 6 cells). Analysis of cats classified as potentially transmissible and non-transmissible found no statistical difference between FFV pVLs. Of 27 FeLV-positive cats diagnosed by serological and/or molecular assays, 26 with available PBMC gDNA were FeLV qPCR-positive with a median pVL of 2.11 log10 copies/cell (1.29 × 10 8 copies/10 6 cells) ( Figure 1B) . Testing of 35 buccal swab gDNA samples identified four qPCR-positive cats with a median FeLV pVL of −0.55 log10 copies/cell (2.91 × 10 5 copies/10 6 cells). abstract: Feline foamy virus (FFV) and feline leukemia virus (FeLV) belong to the Retroviridae family. While disease has not been reported for FFV infection, FeLV infection can cause anemia and immunosuppression (progressive infection). Co-infection with FFV/FeLV allows evaluation of the pathogenic potential and epidemiology of FFV infection in cats with FeLV pathology. Blood and buccal swab samples from 81 cats were collected in Rio de Janeiro. Plasma was serologically tested for FeLV. DNA extracted from peripheral blood mononuclear cells and buccal swabs was used to PCR detect FFV and FeLV. A qPCR was developed to detect and measure FFV proviral loads (pVLs) in cats. FeLV qPCR was performed using previous methods. The median log10 pVL of FFV mono-infected individuals was lower than found in FFV/FeLV co-infected cats in buccal swabs (p = 0.003). We found 78% of cats had detectable buccal FFV DNA in FFV mono-infected and FFV co-infected FeLV-progressive cats, while in FeLV-regressive cats (those without signs of disease) 22% of cats had detectable buccal FFV DNA (p = 0.004). Our results suggest that regressive FeLV infection may reduce FFV saliva transmission, the main mode of FV transmission. We did not find evidence of differences in pathogenicity in FFV mono- and -dually infected cats. In summary, we show that FVs may interact with FeLV within the same host. Our study supports the utility of cats naturally co-infected with retroviruses as a model to investigate the impact of FV on immunocompromised mammalian hosts. url: https://www.ncbi.nlm.nih.gov/pubmed/30544924/ doi: 10.3390/v10120702 id: cord-281837-knswbb2d author: Chang, Chia-Wen title: Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry date: 2012-04-11 words: 4915.0 sentences: 293.0 pages: flesch: 57.0 cache: ./cache/cord-281837-knswbb2d.txt txt: ./txt/cord-281837-knswbb2d.txt summary: An assay to measure the inhibition of virus-induced cell death in RD cells was first employed using 1 mg/mL of herbal extracts followed by EC 50 determination if the candidates possessed antiviral activity from the primary screening. DGFW but not DMSO protected the cells from virus-induced CPE (panel E versus F, Figure 2 ), indicating that DGFW inhibited viral replication. To test the mechanism of inhibition of viral entry into host cells by DGFW, we performed attachment and penetration assays. Unbound DGFW was removed, the cells were then infected with EV71 for 1 h, and the progeny viruses in the cells and culture medium were harvested for plaque assay at 10 h p.i. Similarly, EV71 was pretreated with DGFW or DMSO for 30 min at 37 °C, and the infectivity of the treated virus was then determined by plaque assay (Figure 6 ). A neutralization assay (EC 50 ) was used to test the antiviral efficacy of extracts or compounds by measuring the inhibition of CPE induced by enterovirus on RD cells. abstract: Dried flowers of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) are a Chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. However, the activity of this medicine against enteroviral infections has not been investigated. The water-extract of dried buds of D. genkwa Sieb. et Zucc. (DGFW) was examined against various strains of enterovirus 71 (EV71) by neutralization assay, and its initial mode of action was characterized by time-of-addition assay followed by attachment and penetration assays. Pretreatment of DGFW with virus abolished viral replication, indicating that DGFW inhibits EV71 by targeting the virus. GFW exerts its anti-EV71 effects by inhibiting viral entry without producing cytotoxic side effects and thus provides a potential agent for antiviral chemotherapeutics. url: https://doi.org/10.3390/v4040539 doi: 10.3390/v4040539 id: cord-310255-aixq5mhf author: Charlton, Frank W. title: Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives date: 2020-08-03 words: 5345.0 sentences: 321.0 pages: flesch: 46.0 cache: ./cache/cord-310255-aixq5mhf.txt txt: ./txt/cord-310255-aixq5mhf.txt summary: More recent evidence highlights how viruses can regulate and/or depend on the ion channels expressed by host cells, highlighting them as new host targets for therapeutic intervention (reviewed by Hover et al., 2017) [14] . We then discuss how intracellular ion channels contribute to the Two-pore channels 1 and 2 (TPC1/2) Gunaratne et al., 2018 [34] Severe fever with thrombocytopenia syndrome virus (SFTSV) Unknown channel Li et al., 2019 [35] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Two-pore channel 2 (TPC2) Ou et al., 2020 [36] Bunyamwera orthobunyavirus (BUNV) Two-pore domain K + (K 2P ) Hover et al., 2016/18 [28, 37] Hazara orthonairovirus (HAZV) Unknown K + channel Punch et al., 2017 [38] Charlton et al., 2019 [39] Human immunodeficiency virus (HIV) G-Protein coupled inwardly rectifying K + (GIRK) ATP-sensitive K + K ATP Dubey et al., 2019 [40] Merkel cell polyomavirus (MCPyV) abstract: Ion channels play key roles in almost all facets of cellular physiology and have emerged as key host cell factors for a multitude of viral infections. A catalogue of ion channel-blocking drugs have been shown to possess antiviral activity, some of which are in widespread human usage for ion channel-related diseases, highlighting new potential for drug repurposing. The emergence of ion channel–virus interactions has also revealed the intriguing possibility that channelopathies may explain some commonly observed virus induced pathologies. This field is rapidly evolving and an up-to-date summary of new discoveries can inform future perspectives. We herein discuss the role of ion channels during viral lifecycles, describe the recently identified ion channel drugs that can inhibit viral infections, and highlight the potential contribution of ion channels to virus-mediated disease. url: https://doi.org/10.3390/v12080844 doi: 10.3390/v12080844 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-323995-cpn34j02 author: Chen, Jun title: Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response date: 2017-12-01 words: 8131.0 sentences: 407.0 pages: flesch: 51.0 cache: ./cache/cord-323995-cpn34j02.txt txt: ./txt/cord-323995-cpn34j02.txt summary: To test this hypothesis, we analyzed the kinetics of CypA RNA expression by quantitative real-time PCR, intracellular CypA (inCypA), and secreted CypA (sCypA) protein levels by Western blot analysis following HCMV infection of HFF cells. To test this hypothesis, we analyzed the kinetics of CypA RNA expression by quantitative real-time PCR, intracellular CypA (inCypA), and secreted CypA (sCypA) protein levels by Western blot analysis following HCMV infection of HFF cells. Moreover, we found that endogenous CD147 was targeted by HCMV-encoded miR-US25-1-5p at the 3 UTR, which could replace CD147-specific siRNA mimics in inhibiting the CD147-mediated early innate immune response to HCMV infection ( Figure 4) . Moreover, we found that endogenous CD147 was targeted by HCMV-encoded miR-US25-1-5p at the 3 UTR, which could replace CD147-specific siRNA mimics in inhibiting the CD147-mediated early innate immune response to HCMV infection ( Figure 4) . abstract: Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3′ UTR (Untranslated Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI). The expression and secretion of Cyclophilin A (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases)/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA. url: https://www.ncbi.nlm.nih.gov/pubmed/29194430/ doi: 10.3390/v9120365 id: cord-255683-2eq24jth author: Chen, Weizao title: Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins date: 2010-02-04 words: 5927.0 sentences: 290.0 pages: flesch: 47.0 cache: ./cache/cord-255683-2eq24jth.txt txt: ./txt/cord-255683-2eq24jth.txt summary: Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. To find whether the activity of the antibodies is related to antibody size and how the viral infection could be affected by cross-linking of HIV-1 Envs, we generated a single-chain Fv fragment (scFv) (scFv m19) of m19 and a human IgG1 Fc-fusion protein (m19Fc) of scFv m19; m19 was selected for further characterization because its light chain was relatively less divergent from the germline ( Figure 1b) and was the only one which did not contain any somatic mutations in the CDR3 of the light chain. abstract: Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs) isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on structures containing their epitopes have not been successful for their elicitation. All known broadly neutralizing mAbs (bnmAbs) are immunoglobulin (Ig) Gs (IgGs) and highly somatically hypermutated which could impede their elicitation. Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. These antibodies bound with high affinity to recombinant envelope glycoproteins (gp140s, Envs) of HIV-1 isolates from different clades. They enhanced or did not neutralize infection by some of the HIV-1 primary isolates using CCR5 as a coreceptor but neutralized all CXCR4 isolates tested although weakly. One of these antibodies with relatively low degree of somatic hypermutation was more extensively characterized. It bound to a highly conserved region partially overlapping with the coreceptor binding site and close to but not overlapping with the CD4 binding site. These results suggest the existence of conserved structures that could direct the immune response to non-neutralizing or even enhancing antibodies which may represent a strategy used by the virus to escape neutralizing immune responses. Further studies will show whether such a strategy plays a role in HIV infection of humans, how important that role could be, and what the mechanisms of infection enhancement are. The newly identified mAbs could be used as reagents to further characterize conserved non-neutralizing, weakly neutralizing or enhancing epitopes and modify or remove them from candidate vaccine immunogens. url: https://www.ncbi.nlm.nih.gov/pubmed/21755021/ doi: 10.3390/v2020547 id: cord-296736-jsm6o5pq author: Chidlow, Glenys R. title: An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens date: 2009-06-08 words: 4131.0 sentences: 183.0 pages: flesch: 43.0 cache: ./cache/cord-296736-jsm6o5pq.txt txt: ./txt/cord-296736-jsm6o5pq.txt summary: title: An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens The aim of this study was to modify real-time PCR assays to facilitate the rapid screening of respiratory samples for a comprehensive range of viral and bacterial pathogens. This tandem multiplex real-time PCR assay, in combination with the semi-nested picornavirus and human metapneumovirus PCR assays, tests for 35 respiratory agents from a sample volume of 180µL compared to 720 µL required for the individual assays. Further work is planned to incorporate the picornavirus and human metapneumovirus assays into the tandem multiplex real-time PCR assay, but so far we have been unable to design or use published real-time PCR primers and probes that detect all types of these viruses with the same sensitivity as our nested assays. A tandem multiplex real-time assay is presented which detects a comprehensive range of respiratory pathogens from a specimen sample of 180µL. Multiplex real-time PCR assay for detection of Influenza and human respiratory syncytial viruses abstract: This study used real-time PCR assays to screen small sample volumes for a comprehensive range of 35 respiratory pathogens. Initial thermocycling was limited to 20 cycles to avoid competition for reagents, followed by a secondary real-time multiplex PCR. Supplementary semi-nested human metapneumovirus and picornavirus PCR assays were required to complete the acute respiratory pathogen profile. Potential pathogens were detected in 85 (70%) of pernasal aspirates collected from 121 children with acute respiratory symptoms. Multiple pathogens were detected in 29 (24%) of those samples. The tandem multiplex real-time PCR was an efficient method for the rapid detection of multiple pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/21994537/ doi: 10.3390/v1010042 id: cord-320015-lbr2q4qh author: Chinchar, V. Gregory title: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date: 2011-10-20 words: 9130.0 sentences: 433.0 pages: flesch: 43.0 cache: ./cache/cord-320015-lbr2q4qh.txt txt: ./txt/cord-320015-lbr2q4qh.txt summary: Additional IE and DE proteins include proteins that may play roles in blocking host immune responses such as a virus-encoded, CARD (caspase activation and recruitment domain) motif-containing protein (vCARD), β-hydroxysteroid dehydrogenase (βHSD), and a RNAse III-like protein, catalytic proteins involved in nucleic acid synthesis (Proliferating Cell Nuclear Antigen [PCNA], DNA methyltransferase [DMTase], the large and small subunits of the viral homolog of cellular RNA polymerase II [vPOL-IIα and -IIβ], transcription factor IIS), catalytic proteins that may act to increase dTTP pool sizes and influence host range (deoxyuridine triphosphatase [dUTPase], deoxynucleotide kinase, the large and small subunits of ribonucleotide reductase), and proteins non-essential for replication in vitro, but needed for growth in vivo (the 18K protein) [22] . Lastly, Sample and co-workers observed that KD of the 18K IE protein had no observable effect on viral gene expression or replication in vitro suggesting that, at least in fathead minnow cells, 18K was not required for the production of infectious virions. abstract: Frog virus 3 (FV3) is the best characterized member of the family Iridoviridae. FV3 study has provided insights into the replication of other family members, and has served as a model of viral transcription, genome replication, and virus-mediated host-shutoff. Although the broad outlines of FV3 replication have been elucidated, the precise roles of most viral proteins remain unknown. Current studies using knock down (KD) mediated by antisense morpholino oligonucleotides (asMO) and small, interfering RNAs (siRNA), knock out (KO) following replacement of the targeted gene with a selectable marker by homologous recombination, ectopic viral gene expression, and recombinant viral proteins have enabled researchers to systematically ascertain replicative- and virulence-related gene functions. In addition, the application of molecular tools to ecological studies is providing novel ways for field biologists to identify potential pathogens, quantify infections, and trace the evolution of ecologically important viral species. In this review, we summarize current studies using not only FV3, but also other iridoviruses infecting ectotherms. As described below, general principles ascertained using FV3 served as a model for the family, and studies utilizing other ranaviruses and megalocytiviruses have confirmed and extended our understanding of iridovirus replication. Collectively, these and future efforts will elucidate molecular events in viral replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease. url: https://doi.org/10.3390/v3101959 doi: 10.3390/v3101959 id: cord-258536-qnn9hp8e author: Cong, Yingying title: The Interaction between Nidovirales and Autophagy Components date: 2017-07-11 words: 6566.0 sentences: 358.0 pages: flesch: 44.0 cache: ./cache/cord-258536-qnn9hp8e.txt txt: ./txt/cord-258536-qnn9hp8e.txt summary: The nsp proteins interfere with the host defenses but also induce the formation of double-membrane vesicles (DMVs) and convoluted membranes, on which they collectively form the replication-transcription complexes (RTCs) [19, 20] (Figure 2 , steps 2, 3, and 4). These complexes mediate the synthesis of the genomic RNA and a nested set of subgenomic RNAs that directs the translation of the structural proteins (the nucleocapsid N protein, the membrane M protein, the envelope E protein and the spike S protein) and some accessory proteins, like the hemagglutinin esterase in the case of Severe Acute Respiratory Syndrome (SARS)-CoV or Mouse Hepatitis Virus (MHV) [21] [22] [23] (Figure 2 , steps 5 and 6). Infected cells displayed the presence of a higher number of autophagosome-like double-membrane vesicles, an accumulation of green fluorescent protein (GFP)-LC3-positive puncta and higher levels of lipidated LC3, indicating an induction of autophagy [57] . abstract: Autophagy is a conserved intracellular catabolic pathway that allows cells to maintain homeostasis through the degradation of deleterious components via specialized double-membrane vesicles called autophagosomes. During the past decades, it has been revealed that numerous pathogens, including viruses, usurp autophagy in order to promote their propagation. Nidovirales are an order of enveloped viruses with large single-stranded positive RNA genomes. Four virus families (Arterividae, Coronaviridae, Mesoniviridae, and Roniviridae) are part of this order, which comprises several human and animal pathogens of medical and veterinary importance. In host cells, Nidovirales induce membrane rearrangements including autophagosome formation. The relevance and putative mechanism of autophagy usurpation, however, remain largely elusive. Here, we review the current knowledge about the possible interplay between Nidovirales and autophagy. url: https://www.ncbi.nlm.nih.gov/pubmed/28696396/ doi: 10.3390/v9070182 id: cord-004018-33zi29bg author: Coombs, Kevin M. title: Aptamer Profiling of A549 Cells Infected with Low-Pathogenicity and High-Pathogenicity Influenza Viruses date: 2019-11-05 words: 5373.0 sentences: 252.0 pages: flesch: 43.0 cache: ./cache/cord-004018-33zi29bg.txt txt: ./txt/cord-004018-33zi29bg.txt summary: We used a newly-developed aptamer-based multiplexed technique (SOMAscan(®)) to examine >1300 human lung cell proteins affected by the different IAV strains, and identified more than 500 significantly dysregulated cellular proteins. The PR8 strain induced a general activation, primarily by upregulating many immune molecules, the seasonal RV733 and pdm09 strains had minimal effect upon assayed molecules, and the avian strains induced significant downregulation, primarily in antimicrobial response, cardiovascular and post-translational modification systems. We found that the culture-adapted PR8 strain had an overall activation of immune molecules, the mild seasonal and pdm09 human strains had little effect upon the molecules targeted by the SOMA panel, and the avian H5N1 and H7N9 strains, that are much more pathogenic in humans, had the most dramatic proteomic responses, these upregulating a few tested molecules, but inhibiting many more key cellular processes. Quantitative proteomic analyses of influenza virus-infected cultured human lung cells Quantitative analysis of cellular proteome alterations in human influenza A virus-infected mammalian cell lines abstract: Influenza A viruses (IAVs) are important animal and human emerging and re-emerging pathogens that are responsible for yearly seasonal epidemics and sporadic pandemics. IAVs cause a wide range of clinical illnesses, from relatively mild infections by seasonal strains, to acute respiratory distress during infections with highly pathogenic avian IAVs (HPAI). For this study, we infected A549 human lung cells with lab prototype A/PR/8/34 (H1N1) (PR8), a seasonal H1N1 (RV733), the 2009 pandemic H1N1 (pdm09), or with two avian strains, an H5N1 HPAI strain or an H7N9 strain that has low pathogenicity in birds but high pathogenicity in humans. We used a newly-developed aptamer-based multiplexed technique (SOMAscan(®)) to examine >1300 human lung cell proteins affected by the different IAV strains, and identified more than 500 significantly dysregulated cellular proteins. Our analyses indicated that the avian strains induced more profound changes in the A549 global proteome compared to all tested low-pathogenicity H1N1 strains. The PR8 strain induced a general activation, primarily by upregulating many immune molecules, the seasonal RV733 and pdm09 strains had minimal effect upon assayed molecules, and the avian strains induced significant downregulation, primarily in antimicrobial response, cardiovascular and post-translational modification systems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893437/ doi: 10.3390/v11111028 id: cord-326614-cik3ino6 author: Corder, Brigette N. title: A Decade in Review: A Systematic Review of Universal Influenza Vaccines in Clinical Trials during the 2010 Decade date: 2020-10-20 words: 7511.0 sentences: 488.0 pages: flesch: 46.0 cache: ./cache/cord-326614-cik3ino6.txt txt: ./txt/cord-326614-cik3ino6.txt summary: These trials include a variety of viral targets, vaccine platforms, and adjuvants to boost the immune response to vaccination. Another vaccine utilized the full-length H5 HA protein in an oral recombinant adenovirus type 4 (Ad4) vectored vaccine, Ad4-H5-Vtn. Three clinical trials have enrolled 313 participants between 18 and 49 years of age to investigate this avian H5 influenza vaccine. Although results for the phase II trial have not been posted, a press release from Novavax stated that NanoFlu induced superior HAI antibody responses against homologous and drifted strains compared to the seasonal influenza vaccine. Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: Study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: A phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults abstract: On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010–2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As we look forward, there are currently three vaccines in phase III clinical trials which could provide significant improvement over seasonal influenza vaccines. This systematic review of universal influenza vaccine clinical trials during the 2010–2019 decade provides an update on the progress towards an improved influenza vaccine. url: https://doi.org/10.3390/v12101186 doi: 10.3390/v12101186 id: cord-288058-oilurica author: Cui, Tingting title: Role of Porcine Aminopeptidase N and Sialic Acids in Porcine Coronavirus Infections in Primary Porcine Enterocytes date: 2020-04-05 words: 7087.0 sentences: 331.0 pages: flesch: 52.0 cache: ./cache/cord-288058-oilurica.txt txt: ./txt/cord-288058-oilurica.txt summary: To determine the effect of APN on coronavirus replication, the enterocytes were precultured with 1µg/mL hydrocortisone, 50 µM spermidine, 1 µg/mL insulin, 0.1 µM Wnt agonist, or 1% intestinal contents for 24 h prior to inoculation with PEDV CV777 Vero adapted strain, CV777 fecal suspension, and TGEV Miller. To determine the effect of APN on coronavirus replication, the enterocytes were precultured with 1µg/mL hydrocortisone, 50 µM spermidine, 1 µg/mL insulin, 0.1 µM Wnt agonist, or 1% intestinal contents for 24 h prior to inoculation with PEDV CV777 Vero adapted strain, CV777 fecal suspension, and TGEV Miller. The results show that pretreatment of primary enterocytes with hydrocortisone, spermidine, porcine insulin, Wnt agonist, and intestinal contents could stimulate the expression of APN and enhance the infection of PEDV CV777 Vero adapted and non-adapted strains and the TGEV Miller in the enterocytes. abstract: Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) have been reported to use aminopeptidase N (APN) as a cellular receptor. Recently, the role of APN as a receptor for PEDV has been questioned. In our study, the role of APN in PEDV and TGEV infections was studied in primary porcine enterocytes. After seven days of cultivation, 89% of enterocytes presented microvilli and showed a two- to five-fold higher susceptibility to PEDV and TGEV. A significant increase of PEDV and TGEV infection was correlated with a higher expression of APN, which was indicative that APN plays an important role in porcine coronavirus infections. However, PEDV and TGEV infected both APN positive and negative enterocytes. PEDV and TGEV Miller showed a higher infectivity in APN positive cells than in APN negative cells. In contrast, TGEV Purdue replicated better in APN negative cells. These results show that an additional receptor exists, different from APN for porcine coronaviruses. Subsequently, treatment of enterocytes with neuraminidase (NA) had no effect on infection efficiency of TGEV, implying that terminal cellular sialic acids (SAs) are no receptor determinants for TGEV. Treatment of TGEV with NA significantly enhanced the infection which shows that TGEV is masked by SAs. url: https://www.ncbi.nlm.nih.gov/pubmed/32260595/ doi: 10.3390/v12040402 id: cord-003334-ion97n4b author: De Silva Senapathi, Upasama title: The In Ovo Delivery of CpG Oligonucleotides Protects against Infectious Bronchitis with the Recruitment of Immune Cells into the Respiratory Tract of Chickens date: 2018-11-15 words: 5827.0 sentences: 266.0 pages: flesch: 54.0 cache: ./cache/cord-003334-ion97n4b.txt txt: ./txt/cord-003334-ion97n4b.txt summary: Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown. We found significantly higher survival rates and reduced IBV infection in the chickens following the pre-treatment of the ED 18 eggs with CpG ODNs. At 3 days post infection (dpi), we found an increased recruitment of macrophages, cluster of differentiation (CD)8α+ and CD4+ T lymphocytes, and an up-regulation of interferon (IFN)-γ mRNA in the respiratory tract of the chickens. Considering that we observed a significant reduction in the IBV induced morbidity and mortality of in ovo CpG ODN pre-treated birds correlating with varying degrees of increased macrophages, CD4+, and CD8α+ T cells in the tracheal and lung tissues, we needed to further elucidate the mechanisms by which these immune cells were efficiently recruited. abstract: The in ovo delivery of cytosine-guanosine (CpG) oligodeoxynucleotides (ODNs) protects chickens against many bacterial and viral infections, by activating the toll-like receptor (TLR)21 signaling pathway. Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown. Thus, our objectives were to determine the protective effect of the in ovo delivery of CpG ODNs at ED 18 against IBV infection encountered post-hatch and, then, to investigate the mechanisms of protection. We found significantly higher survival rates and reduced IBV infection in the chickens following the pre-treatment of the ED 18 eggs with CpG ODNs. At 3 days post infection (dpi), we found an increased recruitment of macrophages, cluster of differentiation (CD)8α+ and CD4+ T lymphocytes, and an up-regulation of interferon (IFN)-γ mRNA in the respiratory tract of the chickens. Overall, it may be inferred that CpG ODNs, when delivered in ovo, provide protection against IBV infection induced morbidity and mortality with an enhanced immune response. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266937/ doi: 10.3390/v10110635 id: cord-257539-01s21vh0 author: Delvecchio, Rodrigo title: Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models date: 2016-11-29 words: 5669.0 sentences: 290.0 pages: flesch: 52.0 cache: ./cache/cord-257539-01s21vh0.txt txt: ./txt/cord-257539-01s21vh0.txt summary: Immunofluorescence staining corroborated these results ( Figure 1B ) and additionally, chloroquine decreased the production of infectious ( Figure 1C ) and total ( Figure 1D ) virus particles, including defective viral particles, by ZIKV-infected cells. Incubation of Vero cells with chloroquine at 0 h postinfection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ). To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. To evaluate which step of the viral cycle was susceptible to inhibition, chloroquine was added to Vero cells at different time points post-infection with ZIKV MR766. Incubation of Vero cells with chloroquine at 0 h post-infection had a greater impact on the production of ZIKV particles, decreasing viral RNA 64-fold over the controls ( Figure 3A ). abstract: Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres. url: https://www.ncbi.nlm.nih.gov/pubmed/27916837/ doi: 10.3390/v8120322 id: cord-341138-mxjsp3cm author: Denner, Joachim title: Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV) date: 2016-12-20 words: 4762.0 sentences: 239.0 pages: flesch: 47.0 cache: ./cache/cord-341138-mxjsp3cm.txt txt: ./txt/cord-341138-mxjsp3cm.txt summary: title: Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV) The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. The transspecies transmission of the gibbon ape leukaemia virus (GaLV) and the koala retrovirus (KoRV) is a prime example of a transmission that is still not yet fully understood. Searching for the precursor virus, retroviruses related to KoRV and GaLV have been described in rodents such as South East Asian mice (e.g., Mus caroli [9, 10] and Mus dunni [11] ), as well as in two subspecies of Melomys burtoni in Australia and Indonesia [12, 13] . The nucleotide sequence of koala (Phascolarctos cinereus) retrovirus: A novel type C endogenous virus related to gibbon ape leukemia virus abstract: Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1) is a well-known example. The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. Related retroviruses have been found in Southeast Asian mice although the sequence similarity was limited. Viruses with a higher sequence homology were isolated from Melomys burtoni, the Australian and Indonesian grassland melomys. However, only the habitats of the koalas and the grassland melomys in Australia are overlapping, indicating that the melomys virus may not be the precursor of the GaLV. Viruses closely related to GaLV/KoRV were also detected in bats. Therefore, given the fact that the habitats of the gibbons in Thailand and the koalas in Australia are far away, and that bats are able to fly over long distances, the hypothesis that retroviruses of bats are the origin of GaLV and KoRV deserves consideration. Analysis of previous transspecies transmissions of retroviruses may help to evaluate the potential of transmission of related retroviruses in the future, e.g., that of porcine endogenous retroviruses (PERVs) during xenotransplantation using pig cells, tissues or organs. url: https://www.ncbi.nlm.nih.gov/pubmed/27999419/ doi: 10.3390/v8120336 id: cord-308201-lavcsqov author: Desforges, Marc title: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? date: 2019-12-20 words: 8470.0 sentences: 473.0 pages: flesch: 36.0 cache: ./cache/cord-308201-lavcsqov.txt txt: ./txt/cord-308201-lavcsqov.txt summary: Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Even though no clear cause and effect link has ever been made with the onset of human neurological diseases, their neuropathogenicity is being increasingly recognized in humans, as several recent reports associated cases of encephalitis [244] , acute flaccid paralysis [271] and other neurological symptoms, including possible complications of HCoV infection such as Guillain-Barré syndrome or ADEM [249, [272] [273] [274] [275] [276] [277] [278] [279] . Like for several other respiratory viruses, accumulating evidence now indicate that HCoV are neuroinvasive in humans and we hypothesize that these recognized respiratory pathogens are potentially neurovirulent as well, as they could participate in short-and long-term neurological disorders either as a result of inadequate host immune responses and/or viral propagation in the CNS, which directly induces damage to resident cells. abstract: Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses. url: https://doi.org/10.3390/v12010014 doi: 10.3390/v12010014 id: cord-257913-uf9sx5qi author: Dijkman, Ronald title: Seroconversion to HCoV-NL63 in Rhesus Macaques date: 2009-10-30 words: 2794.0 sentences: 155.0 pages: flesch: 57.0 cache: ./cache/cord-257913-uf9sx5qi.txt txt: ./txt/cord-257913-uf9sx5qi.txt summary: Alternatively, one can establish whether rhesus macaques that are in close contact to humans have experienced a natural HCoV-NL63 infection by investigating the NL63-directed antibody titers in time. In the current study we use the kinetics of the antibody response to HCoV-NL63 to determine whether rhesus macaques encounter natural infections with HCoV-NL63, or related coronaviruses. The first indication of infections with HCoV-NL63-like viruses in rhesus macaques was found when we tested 32 serum samples of 32 monkeys (Table 1 and Figure 1 ). Longitudinal serum samples were available of three rhesus macaques with the highest antibody levels to HCoV-NL63 (numbers 5, 10 and 17). A well-designed follow up through the years with serum and respiratory samples collected on a regular basis would be sufficient to unravel the potential of the human respiratory viruses to infect rhesus macaques. We show here that there are clear signs that Rhesus macaques acquire natural infections with HCoV-NL63, or a serologically very closely related coronavirus. abstract: HCoV-NL63 is a recently identified respiratory virus. Its pathogenesis has not been fully unraveled because an animal model is currently lacking. Here we examined whether rhesus macaques encounter HCoV-NL63 infections during life, by examining the levels of antibodies to HCoV-NL63 in time. The animals were followed for 7 up till 19 years, and in three animals we observed a steep rise in antibodies during follow up, indicative of a natural infection with HCoV-NL63. url: https://www.ncbi.nlm.nih.gov/pubmed/21994563/ doi: 10.3390/v1030647 id: cord-002561-7j43yic1 author: Donato, Celeste title: The Broad Host Range and Genetic Diversity of Mammalian and Avian Astroviruses date: 2017-05-10 words: 7434.0 sentences: 327.0 pages: flesch: 35.0 cache: ./cache/cord-002561-7j43yic1.txt txt: ./txt/cord-002561-7j43yic1.txt summary: Astroviruses within the Mamastrovirus genus are derived from numerous mammalian species in addition to humans (HAstV), including farmed species such as pigs (PAstV), sheep (OAstV), cattle (BoAstV), domesticated animals including cats (FAstV), and dogs (CaAstV), rodents and small mammals including mink (MiAstV), bats (BAstV), rats (RAstV), mice, rabbit (RabAstV), fox, marmot (HHMastV), porcupine, shrew, vole, and larger species including deer (CcAstV), monkeys, water buffalo (BufAstV), yak, camel (DcAstV), and cheetah (ChAstV) (Figure 1a,b) . Viruses from the Avastrovirus genus have been characterized from numerous farmed avian species including turkeys (TAstV), ducks (DAstV), chicken (CAstV), guineafowl (GFAstV), pigeon (PiAstV), goose, as well as wild aquatic and terrestrial birds including heron, doves, penguins, and many other species (Figure 2a) . Astrovirus strains identified from fecal samples of multiple non-human primate species from wild, captive, and peri-urban environments in Bangladesh and Cambodia reveal multiple interspecies transmission events, with viruses closely related to the VA/HMO lineage of human viruses, and non-human mammalian and avian astroviruses (Figure 1a,b) [28] . abstract: Astroviruses are a diverse family of viruses that infect a wide range of mammalian and avian hosts. Here we describe the phylogenetic diversity and current classification methodology of astroviruses based on the ORF1b and ORF2 genes, highlighting the propensity of astroviruses to undergo interspecies transmission and genetic recombination which greatly increase diversity and complicate attempts at a unified and comprehensive classification strategy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454415/ doi: 10.3390/v9050102 id: cord-272666-3uidpr79 author: Doyle, Nicole title: Infectious Bronchitis Virus Nonstructural Protein 4 Alone Induces Membrane Pairing date: 2018-09-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Positive-strand RNA viruses, such as coronaviruses, induce cellular membrane rearrangements during replication to form replication organelles allowing for efficient viral RNA synthesis. Infectious bronchitis virus (IBV), a pathogenic avian Gammacoronavirus of significant importance to the global poultry industry, has been shown to induce the formation of double membrane vesicles (DMVs), zippered endoplasmic reticulum (zER) and tethered vesicles, known as spherules. These membrane rearrangements are virally induced; however, it remains unclear which viral proteins are responsible. In this study, membrane rearrangements induced when expressing viral non-structural proteins (nsps) from two different strains of IBV were compared. Three non-structural transmembrane proteins, nsp3, nsp4, and nsp6, were expressed in cells singularly or in combination and the effects on cellular membranes investigated using electron microscopy and electron tomography. In contrast to previously studied coronaviruses, IBV nsp4 alone is necessary and sufficient to induce membrane pairing; however, expression of the transmembrane proteins together was not sufficient to fully recapitulate DMVs. This indicates that although nsp4 is able to singularly induce membrane pairing, further viral or host factors are required in order to fully assemble IBV replicative structures. This study highlights further differences in the mechanism of membrane rearrangements between members of the coronavirus family. url: https://doi.org/10.3390/v10090477 doi: 10.3390/v10090477 id: cord-334027-xhfmio7k author: Fagre, Anna C. title: Can Bats Serve as Reservoirs for Arboviruses? date: 2019-03-03 words: 8738.0 sentences: 492.0 pages: flesch: 43.0 cache: ./cache/cord-334027-xhfmio7k.txt txt: ./txt/cord-334027-xhfmio7k.txt summary: No demonstrable pathologic effects noted during infection of three bat species [big brown bats (Eptesicus fuscus), little brown bats (Myotis lucifigus) and Mexican free-tailed bats (Tadarida brasiliensie mexicana) with various strains of JBEV or St. Louis encephalitis virus (SLEV) [69] . While experimental data demonstrated that some bat species can sustain JBEV infections and support mosquito-borne transmission of this virus, the epidemiological significance of these observations in the field remains unclear. To truly elucidate the role of bats as reservoirs for arboviruses, field surveillance studies documenting natural infection and transmission dynamics among vector and vertebrate species must be supplemented with experimental infections to characterize viremia profiles and infectiousness to vectors, virus-induced pathology, and immune kinetics following infection. The isolation of Marburg virus from Egyptian rousette bats in Uganda in addition to experimental infections demonstrating viremia and shedding in the absence of overt pathology support the role of this bat species as the reservoir for Marburg virus [6, 7, 208] . abstract: Bats are known to harbor and transmit many emerging and re-emerging viruses, many of which are extremely pathogenic in humans but do not cause overt pathology in their bat reservoir hosts: henipaviruses (Nipah and Hendra), filoviruses (Ebola and Marburg), and coronaviruses (SARS-CoV and MERS-CoV). Direct transmission cycles are often implicated in these outbreaks, with virus shed in bat feces, urine, and saliva. An additional mode of virus transmission between bats and humans requiring further exploration is the spread of disease via arthropod vectors. Despite the shared ecological niches that bats fill with many hematophagous arthropods (e.g., mosquitoes, ticks, biting midges, etc.) known to play a role in the transmission of medically important arboviruses, knowledge surrounding the potential for bats to act as reservoirs for arboviruses is limited. To this end, a comprehensive literature review was undertaken examining the current understanding and potential for bats to act as reservoirs for viruses transmitted by blood-feeding arthropods. Serosurveillance and viral isolation from either free-ranging or captive bats are described in relation to four arboviral groups (Bunyavirales, Flaviviridae, Reoviridae, Togaviridae). Further, ecological associations between bats and hematophagous viral vectors are characterized (e.g., bat bloodmeals in mosquitoes, ingestion of mosquitoes by bats, etc). Lastly, knowledge gaps related to hematophagous ectoparasites (bat bugs and bed bugs (Cimicidae) and bat flies (Nycteribiidae and Streblidae)), in addition to future directions for characterization of bat-vector-virus relationships are described. url: https://doi.org/10.3390/v11030215 doi: 10.3390/v11030215 id: cord-317587-rrx2r4n2 author: Fan, Wensheng title: Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure date: 2019-09-26 words: 9210.0 sentences: 479.0 pages: flesch: 58.0 cache: ./cache/cord-317587-rrx2r4n2.txt txt: ./txt/cord-317587-rrx2r4n2.txt summary: title: Genetic Analysis of Avian Coronavirus Infectious Bronchitis Virus in Yellow Chickens in Southern China over the Past Decade: Revealing the Changes of Genetic Diversity, Dominant Genotypes, and Selection Pressure In conclusion, the IBVs circulating in southern China over the past decade have experienced a remarkable change in genetic diversity, dominant genotypes, and selection pressure, indicating the importance of permanent monitoring of circulating strains and the urgency for developing new vaccines to counteract the emerging LX4-type and New-type IBVs. Infectious bronchitis (IB) is one of the major viral diseases affecting the poultry industry globally. Our results indicated that there was a remarkable change in genetic diversity, dominant genotypes, and selection pressure of IBV strains in southern China over the past decade compared with the previous period of 1985-2007. Molecular characterization of major structural protein genes of avian coronavirus infectious bronchitis virus isolates in southern China abstract: The high mutation rates of infectious bronchitis virus (IBV) pose economic threats to the poultry industry. In order to track the genetic evolutionary of IBV isolates circulating in yellow chickens, we continued to conduct the genetic analyses of the structural genes S1, E, M, and N from 64 IBV isolates in southern China during 2009–2017. The results showed that the dominant genotypes based on the four genes had changed when compared with those during 1985–2008. Based on the S1 gene phylogenetic tree, LX4-type (GI-19) was the most dominant genotype, which was different from that during 1985–2008. The second most dominant genotype was LDT3-A-type, but this genotype disappeared after 2012. New-type 1 (GVI-1) isolates showed increasing tendency and there were four aa (QKEP) located in the hypervariable region (HVR) III and one aa (S) insertion in all the New-type 1 isolates. Both the analyses of amino acid entropy and molecular evolutionary rate revealed that the variations from large to small were S1, E, M, and N. Purifying selection was detected in the S1, E, M, and N gene proteins, which was different from the positive selection during 1985–2008. Six isolates were confirmed to be recombinants, possibly generated from a vaccine virus of the 4/91-type or LDT3-A-type and a circulating virus. The estimated times for the most recent common ancestors based on the S1, E, M, and N genes were the years of 1744, 1893, 1940, and 1945, respectively. Bayesian skyline analysis revealed a sharp decrease in genetic diversity of all the four structural genes after 2010 and since late 2015, the viral population rapidly rose. In conclusion, the IBVs circulating in southern China over the past decade have experienced a remarkable change in genetic diversity, dominant genotypes, and selection pressure, indicating the importance of permanent monitoring of circulating strains and the urgency for developing new vaccines to counteract the emerging LX4-type and New-type IBVs. url: https://www.ncbi.nlm.nih.gov/pubmed/31561498/ doi: 10.3390/v11100898 id: cord-325574-4zf9qtlh author: Farag, Elmoubasher title: Drivers of MERS-CoV Emergence in Qatar date: 2018-12-31 words: 4343.0 sentences: 236.0 pages: flesch: 59.0 cache: ./cache/cord-325574-4zf9qtlh.txt txt: ./txt/cord-325574-4zf9qtlh.txt summary: MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. The transition in husbandry leading to high density camel farming along with increased exposure to humans, combined with the increase of camel movement for the racing and breeding industry, have led to a convergence of factors driving spillover of MERS-CoV from camels to humans. By reviewing changes involving humans and camels over the past 30 years in Qatar, this study sought to identify the key drivers of the emergence and spread of MERS-CoV. The main themes that were covered during the interviews included: (changes in) people''s living conditions; customs and purposes of camel ownership; cultural habits related to camels; educational level and personal behaviors of camel owners and workers; camel movement; demographic distribution of camels in Qatar; camel farming practices: feeding, grazing, and slaughter. abstract: MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. This study sought to identify and quantify possible drivers for the MERS-CoV emergence and spillover to humans. A list of potential human, animal and environmental drivers for disease emergence were identified from literature. Trends in possible drivers were analyzed from national and international databases, and through structured interviews with experts in Qatar. The discovery and exploitation of oil and gas led to a 5-fold increase in Qatar GDP coupled with a 7-fold population growth in the past 30 years. The lifestyle gradually transformed from Bedouin life to urban sedentary life, along with a sharp increase in obesity and other comorbidities. Owing to substantial governmental support, camel husbandry and competitions flourished, exacerbating the already rapidly occurring desertification that forced banning of free grazing in 2005. Consequently, camels were housed in compact barns alongside their workers. The transition in husbandry leading to high density camel farming along with increased exposure to humans, combined with the increase of camel movement for the racing and breeding industry, have led to a convergence of factors driving spillover of MERS-CoV from camels to humans. url: https://www.ncbi.nlm.nih.gov/pubmed/30602691/ doi: 10.3390/v11010022 id: cord-259273-bh5csogu author: Fathima, Sumana title: Use of an Innovative Web-Based Laboratory Surveillance Platform to Analyze Mixed Infections Between Human Metapneumovirus (hMPV) and Other Respiratory Viruses Circulating in Alberta (AB), Canada (2009–2012) date: 2012-11-05 words: 3239.0 sentences: 150.0 pages: flesch: 46.0 cache: ./cache/cord-259273-bh5csogu.txt txt: ./txt/cord-259273-bh5csogu.txt summary: mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. A cost effective approach was adopted in June 2009, to only test specimens negative for both influenza A and B by either singleplex or multiplex real time PCR assays using the Respiratory Virus Panel (RVP) classic assay, a multiplexed assay which detects multiple respiratory viral pathogens including FLUA, FLUB, PIV, ERV, ADV, 4 types of CRV, RSV, and hMPV [15] . In this study we used DIAL to select specimen-based data and investigated the proportions of mono vs mixed infections for hMPV as compared to ADV, CRV, ERV, PIV and RSV for a period of three years, 1 July 2009 to 30 June 2012. abstract: We investigated the proportions of mono vs. mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. Using the Data Integration for Alberta Laboratories (DIAL) platform, 26,226 respiratory specimens at ProvLab between 1 July 2009 and 30 June 2012 were selected and included in the study. Using the Respiratory Virus Panel these specimens tested positive for one or more respiratory virus and negative for influenza A and B. From our subset hMPV was the fourth most common virus (n=2,561) with 373 (15%) identified as mixed infection using DIAL. Mixed infection with hMPV was most commonly found in infants less than 6 months old and ERV was most commonly found in mixed infection with hMPV (230/373, 56%) across all age groups. The proportion of mixed-infection vs. mono-infection was highest for ADV (46%), followed by CRV 229E (32%), CRV HKU1 (31%), CRV NL63 (28%), CRV OC43 (23%), PIV (20%), RSV (17%), hMPV (15%) and ERV (13%). hMPV was significantly more likely to be identified in mono infection as compared with ADV, CRV, PIV, and RSV with the exception of ERV [p<0.05]. url: https://doi.org/10.3390/v4112754 doi: 10.3390/v4112754 id: cord-002994-1zjrunzc author: Faye, Martin title: Full-Genome Characterization and Genetic Evolution of West African Isolates of Bagaza Virus date: 2018-04-13 words: 11495.0 sentences: 517.0 pages: flesch: 45.0 cache: ./cache/cord-002994-1zjrunzc.txt txt: ./txt/cord-002994-1zjrunzc.txt summary: Based on these alignments, we investigated the genetic properties of these different isolates circulating in West Africa, such as genome length and location of main conserved amino acid motifs previously described in mosquito-borne flaviviruses (MBFVs) with sometimes mutations which include no physicochemical properties changes [3] . The RNAz method [21] implemented in the Vienna RNA Websuite (http://rna.tbi.univie.ac.at/) [22] was used to detect thermodynamically stable and evolutionarily conserved structural RNA domains on complete non-coding regions of the 11 West African BAGV isolates characterized in this study and the isolates from Spain and CAR, because complete non-coding sequences are not currently available for the isolate from India. Here, we described location of main conserved amino acid motifs on BAGV proteins using in silico analysis of complete genome sequences of the 11 West African BAGV isolates characterized in this study and sequences from India, CAR and Spain. abstract: Bagaza virus is a mosquito-borne flavivirus, first isolated in 1966 in Central African Republic. It has currently been identified in mosquito pools collected in the field in West and Central Africa. Emergence in wild birds in Europe and serological evidence in encephalitis patients in India raise questions on its genetic evolution and the diversity of isolates circulating in Africa. To better understand genetic diversity and evolution of Bagaza virus, we describe the full-genome characterization of 11 West African isolates, sampled from 1988 to 2014. Parameters such as genetic distances, N-glycosylation patterns, recombination events, selective pressures, and its codon adaptation to human genes are assessed. Our study is noteworthy for the observation of N-glycosylation and recombination in Bagaza virus and provides insight into its Indian origin from the 13th century. Interestingly, evidence of Bagaza virus codon adaptation to human house-keeping genes is also observed to be higher than those of other flaviviruses well known in human infections. Genetic variations on genome of West African Bagaza virus could play an important role in generating diversity and may promote Bagaza virus adaptation to other vertebrates and become an important threat in human health. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923487/ doi: 10.3390/v10040193 id: cord-313439-cadyykks author: Felten, Sandra title: Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature date: 2019-11-15 words: 12466.0 sentences: 522.0 pages: flesch: 44.0 cache: ./cache/cord-313439-cadyykks.txt txt: ./txt/cord-313439-cadyykks.txt summary: Studies evaluating sensitivity and specificity of the detection of serum antibodies in comparison to either histopathology, a combination of diagnostic tests or clinical suspicion of feline infectious peritonitis (FIP). Recent studies evaluated the use of a quantitative RT-PCR (RT-qPCR) to detect FCoV RNA in FNA samples of the mesenteric lymph nodes and other abnormal tissues of clinical cases [119, 140] and hypothesized that this technique would be a useful tool to diagnose FIP for veterinary practitioners, especially in cats without effusion. Sensitivity and specificity from different studies evaluating the detection of feline coronavirus (FCoV) spike (S) gene mutations in tissue samples. RT-nPCR and subsequent S gene sequencing of serum and plasma samples from cats with FIP (diagnosed by histopathology ± IHC or by positive immunofluorescence in effusion) and control cats (diagnosed with another disease either ante or post mortem) revealed a sensitivity of only 7%, which confirms the very low virus load in blood. abstract: Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV) that vary fundamentally in their virulence, but are indistinguishable by a number of diagnostic methods. This review focuses on all important steps every veterinary practitioner has to deal with and new diagnostic tests that can be considered when encountering a cat with suspected FIP with the aim to establish a definitive diagnosis. It gives an overview on all available direct and indirect diagnostic tests and their sensitivity and specificity reported in the literature in different sample material. By providing summarized data for sensitivity and specificity of each diagnostic test and each sample material, which can easily be accessed in tables, this review can help to facilitate the interpretation of different diagnostic tests and raise awareness of their advantages and limitations. Additionally, diagnostic trees depict recommended diagnostic steps that should be performed in cats suspected of having FIP based on their clinical signs or clinicopathologic abnormalities. These steps can easily be followed in clinical practice. url: https://doi.org/10.3390/v11111068 doi: 10.3390/v11111068 id: cord-259237-aty0vrat author: Frabutt, Dylan A. title: Arms Race between Enveloped Viruses and the Host ERAD Machinery date: 2016-09-19 words: 9770.0 sentences: 508.0 pages: flesch: 42.0 cache: ./cache/cord-259237-aty0vrat.txt txt: ./txt/cord-259237-aty0vrat.txt summary: One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. The remaining Man residues are cleaved by the Golgi mannosidases, and the glycan remolding process is continued through the remainder of the N-glycosylation pathway, which generates functional glycoproteins that are delivered to the cell surface ( Figure 1B ). As introduced earlier, the UPR utilizes three different mechanisms to alleviate ER stress: reducing global protein translation, increasing the ER folding capacity, and enhancing ERAD by activating the PERK, ATF6, or IRE1-XBP1 pathways, respectively. ERManI also targets the terminally misfolded human alpha1-antitrypsin variant null (Hong Kong) (NHK) for degradation via ERAD, but neither its catalytic activity nor its catalytic domain is required for this degradation, suggesting that different mechanisms are involved in HIV-1 Env and NHK degradation [152] . The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway abstract: Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during the infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed to potentiate or inhibit viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells. url: https://www.ncbi.nlm.nih.gov/pubmed/27657106/ doi: 10.3390/v8090255 id: cord-320212-fw51w4nm author: Friedman, Stephanie D. title: Genomic Sequences of two Novel Levivirus Single-Stranded RNA Coliphages (Family Leviviridae): Evidence for Recombinationin Environmental Strains date: 2012-09-13 words: 5349.0 sentences: 296.0 pages: flesch: 51.0 cache: ./cache/cord-320212-fw51w4nm.txt txt: ./txt/cord-320212-fw51w4nm.txt summary: When the novel strains were compared to nine Levivirus genogroup I strains, they shared 95–100% similarity among the maturation, capsid and lysis proteins, but only 84–85% in the RNA-dependent RNA polymerase gene. In all analysis programs, the nucleotide or amino acid sequences were aligned to other strains and were therefore approximate positions on the replicase gene. Breakpoint nucleotides for strains DL52 and DL54 (when aligned to genogroup I strains) occurred between nt 84-592 and 84-401, respectively ( Figure 5 a, b) , corresponding to the approximate amino acid breakpoint positions of 133-197 within the replicase gene. Human Noroviruses, a positive sense ssRNA virus with a genome length of 7400-8300 nt, are considered to belong to a prototype strain if they share approximately 85% overall nucleotide sequence identity and a high amino acid sequence identity (>95%) in the polymerase gene [20] . abstract: Bacteriophages are likely the most abundant entities in the aquatic environment, yet knowledge of their ecology is limited. During a fecal source-tracking study, two genetically novel Leviviridae strains were discovered. Although the novel strains were isolated from coastal waters 1130 km apart (North Carolina and Rhode Island, USA), these strains shared 97% nucleotide similarity and 97–100% amino acid similarity. When the novel strains were compared to nine Levivirus genogroup I strains, they shared 95–100% similarity among the maturation, capsid and lysis proteins, but only 84–85% in the RNA-dependent RNA polymerase gene. Further bioinformatic analyses suggested a recombination event occurred. To the best of our knowledge, this is the first description of viral recombinants in environmental Leviviridae ssRNA bacteriophages. url: https://doi.org/10.3390/v4091548 doi: 10.3390/v4091548 id: cord-354068-4qlk6y7h author: Friedrich, Brian M. title: Potential Vaccines and Post-Exposure Treatments for Filovirus Infections date: 2012-09-21 words: 10605.0 sentences: 540.0 pages: flesch: 44.0 cache: ./cache/cord-354068-4qlk6y7h.txt txt: ./txt/cord-354068-4qlk6y7h.txt summary: Due to the difficulties in evaluating wild-type filovirus infection in small animals and the generally high level of immune protection correlates derived from non-human primate (NHP) models of infection, therapeutics and vaccines are ultimately evaluated in NHP species for efficacy against filovirus. In their study, a heterologous prime/boost strategy with recombinant adenovirus serotypes 26 and 35 carrying GP (Z) and GP (S/G) demonstrated complete protection among NHPs. Each of these vectors was capable of stimulating humoral and cell-mediated immune responses in the context of NHPs pre-vaccinated with rAd5 as evidenced by antibody titers reaching an order of magnitude above those achieved in rAd5 vaccinated subjects (1:32,000 compared to 1:6,800), and CD8 + intracellular cytokine staining was 4.7-fold greater among heterologous prime/boosted subjects (0.41% compared to 0.09%) [59] . This GP-Fc fusion protein induced both cell-mediated and humoral immune responses, and mice vaccinated with ZEBOVGP-Fc demonstrated 90% protection against a lethal EBOV challenge. abstract: Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed. url: https://doi.org/10.3390/v4091619 doi: 10.3390/v4091619 id: cord-001974-wjf3c7a7 author: Friis-Nielsen, Jens title: Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers date: 2016-02-19 words: 5773.0 sentences: 348.0 pages: flesch: 48.0 cache: ./cache/cord-001974-wjf3c7a7.txt txt: ./txt/cord-001974-wjf3c7a7.txt summary: Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. The datasets went through a sequential pipeline with modules (in order) of preprocessing, computational subtraction of host sequences, low-complexity sequence removal, sequence assembly, clustering, association to metadata features, and taxonomical annotation. Associations from the shortest mode tended to have higher dispersion in the range of ORs. Furthermore, one block of clustering results using global alignment mode, alignment length based on the shortest contig, and a minimum sequence identity of 90% (c09ˆaSyG1), had an overall high range of ORs as well as the highest minimum values. The clusters are significantly associated with lowest p-values to biological features and the species annotations are described by HMP. abstract: Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776208/ doi: 10.3390/v8020053 id: cord-002589-xq3iq8ai author: Frossard, Jean-Pierre title: UK Pigs at the Time of Slaughter: Investigation into the Correlation of Infection with PRRSV and HEV date: 2017-06-09 words: 3767.0 sentences: 162.0 pages: flesch: 48.0 cache: ./cache/cord-002589-xq3iq8ai.txt txt: ./txt/cord-002589-xq3iq8ai.txt summary: To follow up these studies, we report here on (1) the investigation of PRRSV active infection (RNA in tonsil) using the same 2013 abattoir survey sample-set and (2) an analysis of the correlation of PRRSV and HEV infection in these pigs, which could be of significance for the control of both diseases and in informing farming practices for reducing HEV in the food chain. The phylogenetic trees (Figure 1 ) illustrate the genetic diversity of the ORF5 genes from the 23 samples in this study in comparison to the vaccine virus licensed in the UK at the time and 48 published reference sequences representing the different genotypes and subtypes ( Figure 1A ) and in more detail, in the context of 431 previously sequenced viruses specifically from UK pigs between 1991 and 2014 (unpublished data) ( Figure 1B ). abstract: Hepatitis E virus (HEV) and porcine reproductive and respiratory syndrome virus (PRRSV) and are both globally prevalent in the pig population. While HEV does not cause clinical disease in pigs, its zoonotic potential has raised concerns in the food safety sector. PRRS has become endemic in the United Kingdom (UK) since its introduction in 1991, and continues to cause considerable economic losses to the swine industry. A better understanding of the current prevalence and diversity of PRRSV and HEV in the UK, and their potential association, is needed to assess risks and target control measures appropriately. This study used plasma, tonsil, and cecal content samples previously collected from pigs in 14 abattoirs in England and Northern Ireland to study the prevalence of several pathogens including PRRSV and HEV. The diversity of PRRSV strains detected in these samples was analyzed by sequencing open reading frame 5 (ORF5), revealing no substantial difference in PRRSV strains from these clinically unaffected pigs relative to those from clinical cases of disease in the UK. Despite the potential immuno-modulatory effect of PRRSV infection, previously demonstrated to affect Salmonella and HEV shedding profiles, no significant association was found between positive PRRSV status and positive HEV status. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490802/ doi: 10.3390/v9060110 id: cord-314891-brgtwxhe author: Fumian, Tulio M. title: Potential Therapeutic Agents for Feline Calicivirus Infection date: 2018-08-16 words: 5483.0 sentences: 278.0 pages: flesch: 47.0 cache: ./cache/cord-314891-brgtwxhe.txt txt: ./txt/cord-314891-brgtwxhe.txt summary: Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2′-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC(50) values in the low micromolar range (0.6 μM and 2.5 μM, respectively). The combined inhibitory effects of nitazoxanide (0 to 0.6 µM) and 2CMC (0 to 4 µM) were tested over a range of combinations against FCV in the cell culture using the plaque reduction assay. Of the six NNI compounds tested in the current study, PPNDS and quercetagetin showed an inhibition of FCV RdRp activity with IC 50 values in the low micromolar range (Figure 2 and Table 1 ). Finally, we reported the identification of two compounds (nitazoxanide and 2CMC) with antiviral activity against FCV in cell culture at low micromolar concentrations with a potential combinational therapeutic utility to treat FCV-infected cats. abstract: Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV protease-polymerase protein, we established two in vitro assays to assess the inhibitory activity of compounds directly against the FCV protease or polymerase. Using this recombinant enzyme, we identified quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC(50) values of 2.8 μM and 2.7 μM, respectively). We also demonstrate the inhibition of FCV protease activity by GC376 (IC(50) of 18 µM). Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2′-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC(50) values in the low micromolar range (0.6 μM and 2.5 μM, respectively). In conclusion, we established two in vitro assays that will accelerate the research for FCV antivirals and can be used for the high-throughput screening of direct-acting antivirals. url: https://doi.org/10.3390/v10080433 doi: 10.3390/v10080433 id: cord-004020-qtwcbn7m author: Gao, Yaning title: Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors date: 2019-11-02 words: 7693.0 sentences: 354.0 pages: flesch: 50.0 cache: ./cache/cord-004020-qtwcbn7m.txt txt: ./txt/cord-004020-qtwcbn7m.txt summary: A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Gossypol-treated ZIKV was incubated with Vero E6 cells at 37 • C for 1 h in the presence of DMEM containing serial dilutions of each of the other three natural products identified, such as curcumin, digitonin, and conessine, or anti-ZIKV compound control (bortezomib). Based on Table 1 , four "hit" natural products, including gossypol, curcumin, digitonin, and conessine ( Figure 2A -D), were selected, since they demonstrated inhibitory activity against ZIKV infection with no obvious cytotoxicity in Vero E6 cells when observed under a microscope. Since gossypol demonstrated the highest antiviral activity individually against all ZIKV strains tested, we next investigated the potential combinatorial effects of the combination of gossypol with three other natural products identified, namely curcumin, digitonin, and conessine, as well as anti-ZIKV compound control (bortezomib). abstract: Zika virus (ZIKV) infection during pregnancy leads to severe congenital Zika syndrome, which includes microcephaly and other neurological malformations. No therapeutic agents have, so far, been approved for the treatment of ZIKV infection in humans; as such, there is a need for a continuous effort to develop effective and safe antiviral drugs to treat ZIKV-caused diseases. After screening a natural product library, we have herein identified four natural products with anti-ZIKV activity in Vero E6 cells, including gossypol, curcumin, digitonin, and conessine. Except for curcumin, the other three natural products have not been reported before to have anti-ZIKV activity. Among them, gossypol exhibited the strongest inhibitory activity against almost all 10 ZIKV strains tested, including six recent epidemic human strains. The mechanistic study indicated that gossypol could neutralize ZIKV infection by targeting the envelope protein domain III (EDIII) of ZIKV. In contrast, the other natural products inhibited ZIKV infection by targeting the host cell or cell-associated entry and replication stages of ZIKV. A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Importantly, gossypol also demonstrated marked potency against all four serotypes of dengue virus (DENV) human strains in vitro. Taken together, this study indicates the potential for further development of these natural products, particularly gossypol, as the lead compound or broad-spectrum inhibitors against ZIKV and other flaviviruses, such as DENV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893700/ doi: 10.3390/v11111019 id: cord-011435-x73foqu7 author: Glanz, Anna title: High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication date: 2020-04-14 words: 8401.0 sentences: 469.0 pages: flesch: 39.0 cache: ./cache/cord-011435-x73foqu7.txt txt: ./txt/cord-011435-x73foqu7.txt summary: title: High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication Previously, we uncovered a function for nontranscriptional IRF3 (nt-IRF3), RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA), which triggers apoptotic killing of virus-infected cells. In contrast to the transcriptional pathway, nt-Irf3 in virus-infected cells functions as a chaperone protein by translocating the pro-apoptotic protein BCL2-associated X (BAX) to the mitochondria, thereby causing apoptotic cell death, which we named RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA) ( Figure 1A ) [7] [8] [9] [10] [11] [12] [13] . We validated these results by immunoblot analyses, which demonstrate that doxorubicin treatment inhibited the expression of VSV-G protein, a viral envelope glycoprotein as well as the virus-encoded GFP ( Figure 3B ). We validated these results by immunoblot analyses, which demonstrate that doxorubicin treatment inhibited the expression of VSV-G protein, a viral envelope glycoprotein as well as the virus-encoded GFP ( Figure 3B ). abstract: Interferon (IFN) regulatory factor 3 (IRF3) is the key transcription factor for the induction of IFN and antiviral genes. The absence of antiviral genes in IRF3 deficiency leads to susceptibility to a wide range of viral infections. Previously, we uncovered a function for nontranscriptional IRF3 (nt-IRF3), RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA), which triggers apoptotic killing of virus-infected cells. Using knock-in mice expressing a transcriptionally inactive, but RIPA-active, IRF3 mutant, we demonstrated the relative contribution of RIPA to host antiviral defense. Given that RIPA is a cellular antiviral pathway, we hypothesized that small molecules that promote RIPA in virus-infected cells would act as antiviral agents. To test this, we conducted a high throughput screen of a library of FDA-approved drugs to identify novel RIPA activators. Our screen identified doxorubicin as a potent RIPA-activating agent. In support of our hypothesis, doxorubicin inhibited the replication of vesicular stomatitis virus, a model rhabdovirus, and its antiviral activity depended on its ability to activate IRF3 in RIPA. Surprisingly, doxorubicin inhibited the transcriptional activity of IRF3. The antiviral activity of doxorubicin was expanded to flavivirus and herpesvirus that also activate IRF3. Mechanistically, doxorubicin promoted RIPA by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Finally, we validated these results using another RIPA-activating compound, pyrvinium pamoate, which showed a similar antiviral effect without affecting the transcriptional activity of IRF3. Therefore, we demonstrate that the RIPA branch of IRF3 can be targeted therapeutically to prevent virus infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232324/ doi: 10.3390/v12040442 id: cord-301633-t8s4s0wo author: Gralinski, Lisa E. title: Return of the Coronavirus: 2019-nCoV date: 2020-01-24 words: 3938.0 sentences: 186.0 pages: flesch: 51.0 cache: ./cache/cord-301633-t8s4s0wo.txt txt: ./txt/cord-301633-t8s4s0wo.txt summary: Similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infections, patients exhibited symptoms of viral pneumonia including fever, difficulty breathing, and bilateral lung infiltration in the most severe cases [1] . A range of disease has been observed highlighted by fever, dry cough, shortness of breath, and leukopenia; patients have included mild cases needing supportive care to severe cases requiring extracorporeal membrane oxygenation; however, compared to SARS-CoV (10% mortality) and MERS-CoV (35% mortality), the 2019-nCoV appears to be less virulent at this point with the exception of the elderly and those with underlying health conditions. In the early part of the outbreak, the absence of infection in health care workers argued for inefficient human to human spread and distinguished 2019-nCoV from both SARS-CoV and MERS-CoV. abstract: The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus. url: https://www.ncbi.nlm.nih.gov/pubmed/31991541/ doi: 10.3390/v12020135 id: cord-349011-kxhpdvri author: Grandvaux, Nathalie title: CSV2018: The 2nd Symposium of the Canadian Society for Virology date: 2019-01-18 words: 8844.0 sentences: 375.0 pages: flesch: 42.0 cache: ./cache/cord-349011-kxhpdvri.txt txt: ./txt/cord-349011-kxhpdvri.txt summary: Invited keynote speakers included David Kelvin (Dalhousie University and Shantou University Medical College) who provided a historical perspective on influenza on the 100th anniversary of the 1918 pandemic; Sylvain Moineau (Université Laval) who described CRISPR-Cas systems and anti-CRISPR proteins in warfare between bacteriophages and their host microbes; and Kate O''Brien (then from Johns Hopkins University, now relocated to the World Health Organization where she is Director of Immunization, Vaccines and Biologicals), who discussed the underlying viral etiology for pneumonia in the developing world, and the evidence for respiratory syncytial virus (RSV) as a primary cause. The "Viral Subversion of Host Cell Processes" session also included presentations from the following trainees: Nichole McMullen (Dalhousie University) who reported the unconventional egress mechanisms of non-enveloped reoviruses, Justine Sitz (Université Laval) who described interactions between a human papillomavirus protein and a host DNA repair-specific E3 ubiquitin ligase, and Quentin Osseman (Université de Montréal) who described interactions between respiratory syncytial virus (RSV) and the host autophagy pathway. abstract: The 2nd Symposium of the Canadian Society for Virology (CSV2018) was held in June 2018 in Halifax, Nova Scotia, Canada, as a featured event marking the 200th anniversary of Dalhousie University. CSV2018 attracted 175 attendees from across Canada and around the world, more than double the number that attended the first CSV symposium two years earlier. CSV2018 provided a forum to discuss a wide range of topics in virology including human, veterinary, plant, and microbial pathogens. Invited keynote speakers included David Kelvin (Dalhousie University and Shantou University Medical College) who provided a historical perspective on influenza on the 100th anniversary of the 1918 pandemic; Sylvain Moineau (Université Laval) who described CRISPR-Cas systems and anti-CRISPR proteins in warfare between bacteriophages and their host microbes; and Kate O’Brien (then from Johns Hopkins University, now relocated to the World Health Organization where she is Director of Immunization, Vaccines and Biologicals), who discussed the underlying viral etiology for pneumonia in the developing world, and the evidence for respiratory syncytial virus (RSV) as a primary cause. Reflecting a strong commitment of Canadian virologists to science communication, CSV2018 featured the launch of Halifax’s first annual Soapbox Science event to enable public engagement with female scientists, and the live-taping of the 499th episode of the This Week in Virology (TWIV) podcast, hosted by Vincent Racaniello (Columbia University) and science writer Alan Dove. TWIV featured interviews of CSV co-founders Nathalie Grandvaux (Université de Montréal) and Craig McCormick (Dalhousie University), who discussed the origins and objectives of the new society; Ryan Noyce (University of Alberta), who discussed technical and ethical considerations of synthetic virology; and Kate O’Brien, who discussed vaccines and global health. Finally, because CSV seeks to provide a better future for the next generation of Canadian virologists, the symposium featured a large number of oral and poster presentations from trainees and closed with the awarding of presentation prizes to trainees, followed by a tour of the Halifax Citadel National Historic Site and an evening of entertainment at the historic Alexander Keith’s Brewery. url: https://doi.org/10.3390/v11010079 doi: 10.3390/v11010079 id: cord-254596-wsmnlnlk author: Grädel, Carole title: Whole-Genome Sequencing of Human Enteroviruses from Clinical Samples by Nanopore Direct RNA Sequencing date: 2020-07-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Enteroviruses are small RNA viruses that affect millions of people each year by causing an important burden of disease with a broad spectrum of symptoms. In routine diagnostic laboratories, enteroviruses are identified by PCR-based methods, often combined with partial sequencing for genotyping. In this proof-of-principle study, we assessed direct RNA sequencing (DRS) using nanopore sequencing technology for fast whole-genome sequencing of viruses directly from clinical samples. The approach was complemented by sequencing the corresponding viral cDNA via Illumina MiSeq sequencing. DRS of total RNA extracted from three different enterovirus-positive stool samples produced long RNA fragments, covering between 59% and 99.6% of the most similar reference genome sequences. The identification of the enterovirus sequences in the samples was confirmed by short-read cDNA sequencing. Sequence identity between DRS and Illumina MiSeq enterovirus consensus sequences ranged between 94% and 97%. Here, we show that nanopore DRS can be used to correctly identify enterovirus genotypes from patient stool samples with high viral load and that the approach also provides rich metatranscriptomic information on sample composition for all life domains. url: https://doi.org/10.3390/v12080841 doi: 10.3390/v12080841 id: cord-328259-3g4klpyg author: Guajardo-Leiva, Sergio title: Metagenomic Insights into the Sewage RNA Virosphere of a Large City date: 2020-09-21 words: 7626.0 sentences: 370.0 pages: flesch: 47.0 cache: ./cache/cord-328259-3g4klpyg.txt txt: ./txt/cord-328259-3g4klpyg.txt summary: Despite the overrepresentation of dsRNA viruses, our results show that Santiago''s sewage RNA virosphere was composed mostly of unknown sequences (88%), while known viral sequences were dominated by viruses that infect bacteria (60%), invertebrates (37%) and humans (2.4%). Viral sequences identified as Partitiviridae-like viruses included in the "unclassified RNA viruses ShiM-2016" category in the NCBI taxonomy (~25% abundance; Figure 2B ) and Totiviriade family were also highly abundant in treated and untreated sewage samples from the EU [5, 7] . Therefore, the abundance of these viruses in the Trebal metagenome can expand the known sequence space associated with this family (only 10 genomes are currently available in the NCBI database) and contribute to a better understanding of the bacteriophage biology related to RNA genomes. Taken together, our results show that metagenomic surveys of RNA viruses in sewage samples and the use of HMMs could uncover extraordinary viral diversity through the detection of remote homologs in these human-impacted environments. abstract: Sewage-associated viruses can cause several human and animal diseases, such as gastroenteritis, hepatitis, and respiratory infections. Therefore, their detection in wastewater can reflect current infections within the source population. To date, no viral study has been performed using the sewage of any large South American city. In this study, we used viral metagenomics to obtain a single sample snapshot of the RNA virosphere in the wastewater from Santiago de Chile, the seventh largest city in the Americas. Despite the overrepresentation of dsRNA viruses, our results show that Santiago’s sewage RNA virosphere was composed mostly of unknown sequences (88%), while known viral sequences were dominated by viruses that infect bacteria (60%), invertebrates (37%) and humans (2.4%). Interestingly, we discovered three novel genogroups within the Picobirnaviridae family that can fill major gaps in this taxa’s evolutionary history. We also demonstrated the dominance of emerging Rotavirus genotypes, such as G8 and G6, that have displaced other classical genotypes, which is consistent with recent clinical reports. This study supports the usefulness of sewage viral metagenomics for public health surveillance. Moreover, it demonstrates the need to monitor the viral component during the wastewater treatment and recycling process, where this virome can constitute a reservoir of human pathogens. url: https://doi.org/10.3390/v12091050 doi: 10.3390/v12091050 id: cord-265679-7gzont7l author: Guo, Nan title: Caerin1.1 Suppresses the Growth of Porcine Epidemic Diarrhea Virus In Vitro via Direct Binding to the Virus date: 2018-09-18 words: 5241.0 sentences: 270.0 pages: flesch: 52.0 cache: ./cache/cord-265679-7gzont7l.txt txt: ./txt/cord-265679-7gzont7l.txt summary: In this study, the antiviral activity of a cationic amphibian antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV) was evaluated by an in vitro system using Vero cells. Vero cells cultured in 24-well plates were washed with PBS for 3 times and inoculated respectively with single medium, or single PEDV, or PEDV pre-incubated with different concentrations of Caerin1.1. PEDV suspensions containing different concentrations of Caerin1.1 were pre-incubated for 1 h at 37 • C, and were serially diluted before they were inoculated on the 80% confluent Vero cell monolayers grown in the 96-well plates, followed by washing 3 times with PBS. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1. abstract: Porcine epidemic diarrhea (PED) has re-emerged in recent years and has already caused huge economic losses to the porcine industry all over the world. Therefore, it is urgent for us to find out efficient ways to prevent and control this disease. In this study, the antiviral activity of a cationic amphibian antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV) was evaluated by an in vitro system using Vero cells. We found that even at a very low concentration, Caerin1.1 has the ability to destroy the integrity of the virus particles to block the release of the viruses, resulting in a considerable decrease in PEDV infections. In addition, Caerin1.1 showed powerful antiviral activity without interfering with the binding progress between PEDV and the receptor of the cells, therefore, it could be used as a potential antiviral drug or as a microbicide compound for prevention and control of PEDV. url: https://www.ncbi.nlm.nih.gov/pubmed/30231560/ doi: 10.3390/v10090507 id: cord-279691-v5kpmk0b author: Hagemeijer, Marne C. title: Biogenesis and Dynamics of the Coronavirus Replicative Structures date: 2012-11-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronaviruses are positive-strand RNA viruses that are important infectious agents of both animals and humans. A common feature among positive-strand RNA viruses is their assembly of replication-transcription complexes in association with cytoplasmic membranes. Upon infection, coronaviruses extensively rearrange cellular membranes into organelle-like replicative structures that consist of double-membrane vesicles and convoluted membranes to which the nonstructural proteins involved in RNA synthesis localize. Double-stranded RNA, presumably functioning as replicative intermediate during viral RNA synthesis, has been detected at the double-membrane vesicle interior. Recent studies have provided new insights into the assembly and functioning of the coronavirus replicative structures. This review will summarize the current knowledge on the biogenesis of the replicative structures, the membrane anchoring of the replication-transcription complexes, and the location of viral RNA synthesis, with particular focus on the dynamics of the coronavirus replicative structures and individual replication-associated proteins. url: https://www.ncbi.nlm.nih.gov/pubmed/23202524/ doi: 10.3390/v4113245 id: cord-351760-698voi9y author: Han, Hui-Ju title: Neutralizing Monoclonal Antibodies as Promising Therapeutics against Middle East Respiratory Syndrome Coronavirus Infection date: 2018-11-30 words: 4144.0 sentences: 206.0 pages: flesch: 49.0 cache: ./cache/cord-351760-698voi9y.txt txt: ./txt/cord-351760-698voi9y.txt summary: The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. In vivo study demonstrated that prophylaxis with m336 reduced virus titers in the lung of rabbits infected with MERS-CoV [15] , and m336 also provided transgenic mice expressing human DPP4 with full prophylactic and therapeutic protection from MERS-CoV [16] . A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein Prophylaxis with a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection Passive Transfer of a Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV abstract: Since emerging in 2012, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has been a global public health threat with a high fatality rate and worldwide distribution. There are no approved vaccines or therapies for MERS until now. Passive immunotherapy with neutralizing monoclonal antibodies (mAbs) is an effective prophylactic and therapeutic reagent against emerging viruses. In this article, we review current advances in neutralizing mAbs against MERS-CoV. The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. A major problem with neutralizing mAb therapy is mutant escape under selective pressure, which can be solved by combination of neutralizing mAbs targeting different epitopes. Neutralizing mAbs are currently under preclinical evaluation, and they are promising candidate therapeutic agents against MERS-CoV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/30513619/ doi: 10.3390/v10120680 id: cord-309623-2ngr682l author: Han, Xiaoxiao title: Infectious Bronchitis Virus Infection Induces Apoptosis during Replication in Chicken Macrophage HD11 Cells date: 2017-07-26 words: 5618.0 sentences: 317.0 pages: flesch: 46.0 cache: ./cache/cord-309623-2ngr682l.txt txt: ./txt/cord-309623-2ngr682l.txt summary: Previous studies have reported that infectious bronchitis virus (IBV) infection can produce cytopathic effects (CPE) and apoptosis in some mammalian cells and primary cells. The Beaudette strains were used previously to study the resistance of IBV to the antiviral state induced by type I interferon (IFN) [7] , induction of apoptosis through endoplasmic reticulum stress in Vero cells by IBV infection [8] and activate autophagy by IBV nonstructural protein (NSP) 6 [9] . The rate of apoptosis significantly increased at 12 h.p.i. in virus-infected cells when compared with the mockInfection of HD11 cells with IBV Beaudette caused cell death in a time-and dose-dependent manner, as tested by CCK-8 assay. The results also showed that activation of caspase-9 in IBV Beaudette-infected cells was regulated by decreased expression of Bcl-2 and increased expression of Bax. The caspase-3 activation and virus-induced apoptosis might be triggered through both extrinsic and intrinsic pathways. abstract: Avian infectious bronchitis has caused huge economic losses in the poultry industry. Previous studies have reported that infectious bronchitis virus (IBV) infection can produce cytopathic effects (CPE) and apoptosis in some mammalian cells and primary cells. However, there is little research on IBV-induced immune cell apoptosis. In this study, chicken macrophage HD11 cells were established as a cellular model that is permissive to IBV infection. Then, IBV-induced apoptosis was observed through a cell viability assay, morphological changes, and flow cytometry. The activity of caspases, the inhibitory efficacy of caspase-inhibitors and the expression of apoptotic genes further suggested the activation of apoptosis through both intrinsic and extrinsic pathways in IBV-infected HD11 cells. Additionally, ammonium chloride (NH(4)Cl) pretreated HD11 cells blocked IBV from entering cells and inhibited IBV-induced apoptosis. UV-inactivated IBV also lost the ability of apoptosis induction. IBV replication was increased by blocking caspase activation. This study presents a chicken macrophage cell line that will enable further analysis of IBV infection and offers novel insights into the mechanisms of IBV-induced apoptosis in immune cells. url: https://www.ncbi.nlm.nih.gov/pubmed/28933760/ doi: 10.3390/v9080198 id: cord-013177-whd0znan author: Han, Zhenzhi title: The Husavirus Posa-Like Viruses in China, and a New Group of Picornavirales date: 2020-09-07 words: 5049.0 sentences: 265.0 pages: flesch: 44.0 cache: ./cache/cord-013177-whd0znan.txt txt: ./txt/cord-013177-whd0znan.txt summary: Novel posa-like viral genomes were first identified in swine fecal samples using metagenomics and were designated as unclassified viruses in the order Picornavirales. These posa-like viruses have undergone a complex evolutionary process, and have a wide geographic distribution, complex host spectrum, deep phylogenetic divergence, and diverse genomic organizations. Novel posa-like virus genomes were first identified in swine fecal samples using metagenomics and were assigned as unclassified viruses to the order Picornavirales [12] . Further reports of novel posaviruses with low amino acid sequence identity revealed novel genomic organization features and phylogenetic characteristics of posa-like viruses [15, 16] . Due to the low genomic sequence similarity between the husavirus and unclassified posa-like viruses in Picornavirales, it was difficult to perform a phylogenetic analysis at the full-length genome level. Posa-like viruses identified in previous reports and in the present study formed a single group and clustered with the genomes of family Marnaviridae (Figure 4) . abstract: Novel posa-like viral genomes were first identified in swine fecal samples using metagenomics and were designated as unclassified viruses in the order Picornavirales. In the present study, nine husavirus strains were identified in China. Their genomes share 94.1–99.9% similarity, and alignment of these nine husavirus strains identified 697 nucleotide polymorphism sites across their full-length genomes. These nine strains were directly clustered with the Husavirus 1 lineage, and their genomic arrangement showed similar characteristics. These posa-like viruses have undergone a complex evolutionary process, and have a wide geographic distribution, complex host spectrum, deep phylogenetic divergence, and diverse genomic organizations. The clade of posa-like viruses forms a single group, which is evolutionarily distinct from other known families and could represent a distinct family within the Picornavirales. The genomic arrangement of Picornavirales and the new posa-like viruses are different, whereas the posa-like viruses have genomic modules similar to the families Dicistroviridae and Marnaviridae. The present study provides valuable genetic evidence of husaviruses in China, and clarifies the phylogenetic dynamics and the evolutionary characteristics of Picornavirales. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551994/ doi: 10.3390/v12090995 id: cord-273777-qb0vp9gr author: Happel, Anna-Ursula title: The Vaginal Virome—Balancing Female Genital Tract Bacteriome, Mucosal Immunity, and Sexual and Reproductive Health Outcomes? date: 2020-07-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Besides bacteria, fungi, protists and archaea, the vaginal ecosystem also contains a range of prokaryote- and eukaryote-infecting viruses, which are collectively referred to as the “virome”. Despite its well-described role in the gut and other environmental niches, the vaginal virome remains understudied. With a focus on sexual and reproductive health, we summarize the currently known components of the vaginal virome, its relationship with other constituents of the vaginal microbiota and its association with adverse health outcomes. While a range of eukaryote-infecting viruses has been described to be present in the female genital tract (FGT), few prokaryote-infecting viruses have been described. Literature suggests that various vaginal viruses interact with vaginal bacterial microbiota and host immunity and that any imbalance thereof may contribute to the risk of adverse reproductive health outcomes, including infertility and adverse birth outcomes. Current limitations of vaginal virome research include experimental and analytical constraints. Considering the vaginal virome may represent the missing link in our understanding of the relationship between FGT bacteria, mucosal immunity, and adverse sexual and reproductive health outcomes, future studies evaluating the vaginal microbiome and its population dynamics holistically will be important for understanding the role of the vaginal virome in balancing health and disease. url: https://doi.org/10.3390/v12080832 doi: 10.3390/v12080832 id: cord-343690-rafvxgx1 author: Hartmann, Katrin title: Clinical Aspects of Feline Retroviruses: A Review date: 2012-10-31 words: 10289.0 sentences: 498.0 pages: flesch: 35.0 cache: ./cache/cord-343690-rafvxgx1.txt txt: ./txt/cord-343690-rafvxgx1.txt summary: Although FIV can cause an acquired immunodeficiency syndrome in cats ("feline AIDS") comparable to human immunodeficiency virus (HIV) infection in humans, with increased risk for opportunistic infections, neurologic diseases, and tumors, in most naturally infected cats, FIV does not cause a severe clinical syndrome. Experimental FIV infection also progresses through several stages, similar to HIV infection in people, including an acute phase, a clinically asymptomatic phase of variable duration, and a terminal phase sometimes called "feline acquired immunodeficiency syndrome" ("AIDS") [18, 19] . Of 8642 FeLV-infected cats presented to North American Veterinary Teaching Hospitals, various co-infections (including FIV infection, feline infectious peritonitis (FIP), upper respiratory infection, hemotropic mycoplasmosis, and stomatitis) were the most frequent findings (15%), followed by anemia (11%), lymphoma (6%), leukopenia or thrombocytopenia (5%), and leukemia or myeloproliferative diseases (4%) [20] . An early defect in primary and secondary t cell responses in asymptomatic cats during acute feline immunodeficiency virus (fiv) infection abstract: Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests) also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats. url: https://www.ncbi.nlm.nih.gov/pubmed/23202500/ doi: 10.3390/v4112684 id: cord-261417-4pf5nsw2 author: Harwig, Alex title: The Battle of RNA Synthesis: Virus versus Host date: 2017-10-21 words: 7864.0 sentences: 443.0 pages: flesch: 53.0 cache: ./cache/cord-261417-4pf5nsw2.txt txt: ./txt/cord-261417-4pf5nsw2.txt summary: Why the virus prefers to use these snRNAs as targets has yet to be experimentally established, but it has been proposed that the selective de-capping of U1 and U2 RNAs in combination with the binding of the viral NS1 protein to U6 snRNA may serve to inhibit host pre-mRNA splicing [66] . The folding of the TAR hairpin is key to the regulation of HIV-1 transcription [94] as it is used as a scaffold to recruit essential transcription factors, including the 86-101 amino acid (aa) viral trans-activator protein (Tat) [83] ( Figure 3C ). Interestingly, the human T-lymphotropic virus type 1 transcriptional activator Tax also utilizes P-TEFb for viral transcription and displaces P-TEFb from 7SK snRNP through binding CycT1 [101, 102] , suggesting that P-TEFb liberation from 7SK snRNP could be a common theme developed by different viruses to support their replication in host cells. abstract: Transcription control is the foundation of gene regulation. Whereas a cell is fully equipped for this task, viruses often depend on the host to supply tools for their transcription program. Over the course of evolution and adaptation, viruses have found diverse ways to optimally exploit cellular host processes such as transcription to their own benefit. Just as cells are increasingly understood to employ nascent RNAs in transcription regulation, recent discoveries are revealing how viruses use nascent RNAs to benefit their own gene expression. In this review, we first outline the two different transcription programs used by viruses, i.e., transcription (DNA-dependent) and RNA-dependent RNA synthesis. Subsequently, we use the distinct stages (initiation, elongation, termination) to describe the latest insights into nascent RNA-mediated regulation in the context of each relevant stage. url: https://www.ncbi.nlm.nih.gov/pubmed/29065472/ doi: 10.3390/v9100309 id: cord-292364-jhiimglg author: Hayakawa, Jun title: Genetic and Antigenic Characterization and Retrospective Surveillance of Bovine Influenza D Viruses Identified in Hokkaido, Japan from 2018 to 2020 date: 2020-08-11 words: 4375.0 sentences: 208.0 pages: flesch: 49.0 cache: ./cache/cord-292364-jhiimglg.txt txt: ./txt/cord-292364-jhiimglg.txt summary: Comparative and phylogenetic analyses using sequence data of the three BIDVs and IDVs from Japan and other countries available in GenBank demonstrated that Japanese BIDVs, including the three BIDV isolates, were genetically distinct from other IDVs. Genotype classifications based on the rotavirus genotype classification revealed multiple genotypes of RNA segments 1–7. Our findings suggest that BIDVs of different genotypes and antigenicity are distributed and maintained in Hokkaido and provide new insights into molecular characteristics and the evolution of IDVs. Influenza viruses are enveloped, segmented, single-stranded, negative-sense RNA viruses, which belong to the family Orthomyxoviridae, and are currently classified into the following four species: influenza A, B, C, and D (IAV-IDV). Viral neutralizing antibody titers of serum samples collected in the acute (pre) and recovery (post) phases of BRD outbreaks that occurred at farms A and B against bovine influenza D viruses (HKD1 and HKD2) isolated from the two farms, as measured using a neutralization assay. abstract: Influenza D virus (IDV), which is a new member of the Orthomyxoviridae family, is potentially involved in bovine respiratory diseases (BRDs). Bovine IDVs (BIDVs) from Japan have been distributed nationwide since 2010 and are genetically distinct from foreign IDVs. We isolated BIDVs from three BRD outbreaks, in Hokkaido during 2018–2020, to understand their genetic and antigenic characteristics. Retrospective surveillance was performed using sera collected throughout the last decade in Hokkaido to investigate BIDV existence. Three BIDVs were isolated using cell culture. Comparative and phylogenetic analyses using sequence data of the three BIDVs and IDVs from Japan and other countries available in GenBank demonstrated that Japanese BIDVs, including the three BIDV isolates, were genetically distinct from other IDVs. Genotype classifications based on the rotavirus genotype classification revealed multiple genotypes of RNA segments 1–7. Two BIDVs were of a new genotype, different from those of other Japanese BIDVs. Neutralization assays against two BIDVs with different genotypes using sera collected in acute and recovery phases of BRD revealed differences in cross-reactivity to heterogenous BIDVs. Retrospective surveillance suggested that BIDV existed in Hokkaido, in 2009. Our findings suggest that BIDVs of different genotypes and antigenicity are distributed and maintained in Hokkaido and provide new insights into molecular characteristics and the evolution of IDVs. url: https://www.ncbi.nlm.nih.gov/pubmed/32796617/ doi: 10.3390/v12080877 id: cord-272459-w14finxf author: Heaton, Nicholas S. title: Dengue Virus and Autophagy date: 2011-08-04 words: 3107.0 sentences: 182.0 pages: flesch: 40.0 cache: ./cache/cord-272459-w14finxf.txt txt: ./txt/cord-272459-w14finxf.txt summary: Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. Relevant to DENV infection, a type of selective autophagy termed lipophagy was described, wherein autophagosomes can target cellular stores of lipids known as lipid droplets (LDs) to generate energy for the cell [38] . In subsequent work, the authors reproduced the published results that DENV induces and requires autophagy for robust viral replication [39] . These autophagosomes did not co-localize with markers of the viral replication complex, suggesting that they may play an indirect, non-structural role in DENV replication. Alternatively, DENV infection induces a selective autophagy that is preferentially targeted to lipid droplets, which leads to changes in cellular metabolism. More work, however, is required to show whether the proposed viral triggers of autophagy reproduce all cellular signals and phenotypes that accompany autophagy induction in DENV-infected cells. abstract: Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV). Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomography of DENV replication complexes showed that DENV replicates on endoplasmic reticulum (ER) cisternae invaginations and not on classical autophagosomes. Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. DENV-induced autophagosomes deplete cellular triglycerides that are stored in lipid droplets, leading to increased β-oxidation and energy production. This is the first example of a virus triggering autophagy to modulate cellular physiology. In this review, we summarize these data and discuss new questions and implications for autophagy during DENV replication. url: https://www.ncbi.nlm.nih.gov/pubmed/21994782/ doi: 10.3390/v3081332 id: cord-332915-4o2dsf56 author: Hong, Seung-Min title: Pathobiological and Genomic Characterization of a Cold-Adapted Infectious Bronchitis Virus (BP-caKII) date: 2018-11-19 words: 5904.0 sentences: 310.0 pages: flesch: 56.0 cache: ./cache/cord-332915-4o2dsf56.txt txt: ./txt/cord-332915-4o2dsf56.txt summary: We established a cold-adapted infectious bronchitis virus (BP-caKII) by passaging a field virus through specific pathogen-free embryonated eggs 20 times at 32 °C. In this study, we established a cold-adapted IBV (BP-caKII), and we characterized its pathogenicity in embryos and chickens, tissue tropism, and persistence of infection. We applied a premature reproductive tract pathogenicity model to the differentiation of the pathogenicity of IBVs and performed comparative genomics to shed light on the genetic background of the embryo adaptation of K2 and the cold adaptation of BP-caKII. To test virus titer and embryo pathogenicity, BP-caKII was inoculated into 10-day-old SPF embryonated eggs (Valo Biomedia) via the allantoic cavity route and incubated at 37 • C for 48 h. SNU9106 was passaged 20 times through three embryonated eggs by inoculating allantoic fluid with high virus titer, and BP-caKII was established. SNU9106 was passaged 20 times through three embryonated eggs by inoculating allantoic fluid with high virus titer, and BP-caKII was established. abstract: We established a cold-adapted infectious bronchitis virus (BP-caKII) by passaging a field virus through specific pathogen-free embryonated eggs 20 times at 32 °C. We characterized its growth kinetics and pathogenicity in embryonated eggs, and its tropism and persistence in different tissues from chickens; then, we evaluated pathogenicity by using a new premature reproductive tract pathogenicity model. Furthermore, we determined the complete genomic sequence of BP-caKII to understand the genetic changes related to cold adaptation. According to our results, BP-caKII clustered with the KII genotype viruses K2 and KM91, and showed less pathogenicity than K2, a live attenuated vaccine strain. BP-caKII showed delayed viremia, resulting in its delayed dissemination to the kidneys and cecal tonsils compared to K2 and KM91, the latter of which is a pathogenic field strain. A comparative genomics study revealed similar nucleotide sequences between BP-caKII, K2 and KM91 but clearly showed different mutations among them. BP-caKII shared several mutations with K2 (nsp13, 14, 15 and 16) following embryo adaptation but acquired multiple additional mutations in nonstructural proteins (nsp3, 4 and 12), spike proteins and nucleocapsid proteins following cold adaptation. Thus, the establishment of BP-caKII and the identified mutations in this study may provide insight into the genetic background of embryo and cold adaptations, and the attenuation of coronaviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/30463206/ doi: 10.3390/v10110652 id: cord-254250-l0v602x9 author: Hooper, Chantelle title: A Novel RNA Virus, Macrobrachium rosenbergii Golda Virus (MrGV), Linked to Mass Mortalities of the Larval Giant Freshwater Prawn in Bangladesh date: 2020-10-02 words: 6440.0 sentences: 309.0 pages: flesch: 48.0 cache: ./cache/cord-254250-l0v602x9.txt txt: ./txt/cord-254250-l0v602x9.txt summary: title: A Novel RNA Virus, Macrobrachium rosenbergii Golda Virus (MrGV), Linked to Mass Mortalities of the Larval Giant Freshwater Prawn in Bangladesh De novo virus assembly revealed a 29 kb single-stranded positive-sense RNA virus with similarities in key protein motif sequences to yellow head virus (YHV), an RNA virus that causes mass mortalities in marine shrimp aquaculture, and other viruses in the Nidovirales order. rnaSPAdes assembly of combined libraries produced 38,826 contigs; 23 contigs, of average length 4560 bp, had similarity in protein sequence to YHV or gill-associated virus (GAV), but when the trimmed reads were aligned against the YHV genome (accession number GCA_003972805.1), no alignment was seen. rosenbergii were negative: MrNV and XSV, the causative agents of white tail disease [9, 10] ; MrTV, a virus associated with mass larval mortalities in China [15] , Spiroplasma eriocheiris [8] , and WSSV-shown to be able to infect M. abstract: Mass mortalities of the larval stage of the giant freshwater prawn, Macrobrachium rosenbergii, have been occurring in Bangladesh since 2011. Mortalities can reach 100% and have resulted in an 80% decline in the number of hatcheries actively producing M. rosenbergii. To investigate a causative agent for the mortalities, a disease challenge was carried out using infected material from a hatchery experiencing mortalities. Moribund larvae from the challenge were prepared for metatranscriptomic sequencing. De novo virus assembly revealed a 29 kb single-stranded positive-sense RNA virus with similarities in key protein motif sequences to yellow head virus (YHV), an RNA virus that causes mass mortalities in marine shrimp aquaculture, and other viruses in the Nidovirales order. Primers were designed against the novel virus and used to screen cDNA from larvae sampled from hatcheries in the South of Bangladesh from two consecutive years. Larvae from all hatcheries screened from both years were positive by PCR for the novel virus, including larvae from a hatchery that at the point of sampling appeared healthy, but later experienced mortalities. These screens suggest that the virus is widespread in M. rosenbergii hatchery culture in southern Bangladesh, and that early detection of the virus can be achieved by PCR. The hypothesised protein motifs of Macrobrachium rosenbergii golda virus (MrGV) suggest that it is likely to be a new species within the Nidovirales order. Biosecurity measures should be taken in order to mitigate global spread through the movement of post-larvae within and between countries, which has previously been linked to other virus outbreaks in crustacean aquaculture. url: https://doi.org/10.3390/v12101120 doi: 10.3390/v12101120 id: cord-002691-synm1cyw author: Hou, Jiun-Nan title: PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication date: 2017-09-20 words: 9842.0 sentences: 477.0 pages: flesch: 51.0 cache: ./cache/cord-002691-synm1cyw.txt txt: ./txt/cord-002691-synm1cyw.txt summary: title: PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication Results revealed that the TOR signaling pathway may have retained its activity involved in controlling cap-dependent protein translation in C6/36 cells infected by the DENV2. Results revealed that the TOR signaling pathway may have retained its activity involved in controlling cap-dependent protein translation in C6/36 cells infected by the DENV2. This suggested that the PERK signaling pathway is involved in regulating cellular protein translation when ER stress is induced by DENV2 in mosquito cells. This suggested that the PERK signaling pathway is involved in regulating cellular protein translation when ER stress is induced by DENV2 in mosquito cells. In the meantime, PERK inhibition in this study was further shown to increase MMP changes and ROS accumulation, indicating that DENV2-induced ER stress may be reduced by activating the PERK signal pathway since such cellular responses were not evidently shown in uninfected PERKi-treated cells (Figures S1-S3) . abstract: Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5′-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells. This suggests that most mosquito proteins are synthesized via canonical cap-dependent translation. When the PERK signal pathway was inhibited, both accumulation of reactive oxygen species and changes in the mitochondrial membrane potential increased. This suggested that ER stress response was alleviated through the PERK-mediated shutdown of global proteins in DENV2-infected C6/36 cells. In the meantime, the activities of caspases-9 and -3 and the apoptosis-related cell death rate increased in C6/36 cells with PERK inhibition. This reflected that the PERK-signaling pathway is involved in determining cell survival, presumably by reducing DENV2-induced ER stress. Looking at the PERK downstream target, α-subunit of eukaryotic initiation factor 2 (eIF2α), an increased phosphorylation status was only shown in infected C6/36 cells. This indicated that recruitment of ribosome binding to the mRNA 5′-cap structure could have been impaired in cap-dependent translation. It turned out that shutdown of cellular protein translation resulted in a pro-survival effect on mosquito cells in response to DENV2 infection. As synthesis of viral proteins was not affected by the PERK signal pathway, an alternate mode other than cap-dependent translation may be utilized. This finding provides insights into elucidating how the PERK signal pathway modulates dynamic translation of proteins and helps mosquito cells survive continuous replication of the DENV2. It was ecologically important for virus amplification in mosquitoes and transmission to humans. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618028/ doi: 10.3390/v9090262 id: cord-013178-li1x1m25 author: Hung, Ling-Chu title: The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells date: 2020-08-29 words: 9764.0 sentences: 534.0 pages: flesch: 59.0 cache: ./cache/cord-013178-li1x1m25.txt txt: ./txt/cord-013178-li1x1m25.txt summary: title: The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells The purpose of this study in the context of the open reading frame 3 (ORF3) protein of porcine circovirus type 2 (PCV2) was especially its location and its relation to the capsid protein and the apoptosis protein in PCV2-infected porcine peripheral blood mononuclear cells (PBMCs). The mAb 7D3 binds to the ORF3 peptide (residues 35–66) and the native ORF3 protein in PCV2-infected PBMCs, as shown by immunofluorescence assay (IFA). Overall, this study provides a blueprint to explore the ORF3 protein in PCV2-infected PBMCs. The Porcine circovirus (PCV) is a small virus and contains closed circular single-stranded DNA [1] . For these purposes, this study used the commercial capsid antigen-ELISA and homemade ORF3 protein-ELISA (anti-N1 polyclonal antibodies and mAb 7D3 based) to detect viral proteins in pig blood. abstract: The purpose of this study in the context of the open reading frame 3 (ORF3) protein of porcine circovirus type 2 (PCV2) was especially its location and its relation to the capsid protein and the apoptosis protein in PCV2-infected porcine peripheral blood mononuclear cells (PBMCs). To detect the ORF3 protein, monoclonal antibodies (mAbs) were generated in this study. The mAb 7D3 binds to the ORF3 peptide (residues 35–66) and the native ORF3 protein in PCV2-infected PBMCs, as shown by immunofluorescence assay (IFA). The data show that 3–5% of PBMCs were positive for ORF3 protein or p53 protein. Further, 78–82% of PBMCs were positive for the capsid. This study confirmed the ORF3 protein not only colocalized with the capsid protein but also colocalized with the p53 protein in PBMCs. Immunoassays were conducted in this study to detect the capsid protein, the ORF3 protein, anti-capsid IgG, and anti-ORF3 IgG. The data show the correlation (r = 0.758) of the ORF3 protein and the capsid protein in the blood samples from the PCV2-infected herd. However, each anti-viral protein IgG had a different curve of the profile in the same herd after vaccination. Overall, this study provides a blueprint to explore the ORF3 protein in PCV2-infected PBMCs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551997/ doi: 10.3390/v12090961 id: cord-003407-f5v3hhr8 author: Hung, Ting-Chun title: Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection date: 2018-11-27 words: 4790.0 sentences: 203.0 pages: flesch: 41.0 cache: ./cache/cord-003407-f5v3hhr8.txt txt: ./txt/cord-003407-f5v3hhr8.txt summary: Thus, RC''s anti-HCV activity appeared strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. Viruses 2018, 10, x FOR PEER REVIEW 6 of 12 strongest when concurrently present on the host cell with the viral particles, suggesting that its inhibitory effect mainly targeted the early phase of the HCV infection, including viral entry. To further characterize the mechanism(s) underlying RC''s anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry. To further characterize the mechanism(s) underlying RC''s anti-HCV effect, which was strongest when RC was simultaneously present with the virus on the host cell surface, we performed a synchronized infection assay on early viral entry. abstract: Hepatitis C Virus (HCV) remains an important public health threat with approximately 170 million carriers worldwide who are at risk of developing hepatitis C-associated end-stage liver diseases. Despite improvement of HCV treatment using the novel direct-acting antivirals (DAAs) targeting viral replication, there is a lack of prophylactic measures for protection against HCV infection. Identifying novel antivirals such as those that target viral entry could help broaden the therapeutic arsenal against HCV. Herein, we investigated the anti-HCV activity of the methanolic extract from Rhizoma coptidis (RC), a widely used traditional Chinese medicine documented by the WHO and experimentally reported to possess several pharmacological functions including antiviral effects. Using the cell culture-derived HCV system, we demonstrated that RC dose-dependently inhibited HCV infection of Huh-7.5 cells at non-cytotoxic concentrations. In particular, RC blocked HCV attachment and entry/fusion into the host cells without exerting any significant effect on the cell-free viral particles or modulating key host cell entry factors to HCV. Moreover, RC robustly suppressed HCV pseudoparticles infection of Huh-7.5 cells and impeded infection by several HCV genotypes. Collectively, our results identified RC as a potent antagonist to HCV entry with potential pan-genotypic properties, which deserves further evaluation for use as an anti-HCV agent. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315547/ doi: 10.3390/v10120669 id: cord-311205-3uwiys4a author: Hung, Yu-Fu title: Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes date: 2015-07-21 words: 4604.0 sentences: 231.0 pages: flesch: 53.0 cache: ./cache/cord-311205-3uwiys4a.txt txt: ./txt/cord-311205-3uwiys4a.txt summary: In addition, amino acid residues of the central region of some NS4A peptides might bind directly to the liposome leading to the disappearance of the corresponding NMR signals. In addition, amino acid residues of the central region of some NS4A peptides might bind directly to the liposome leading to the disappearance of the corresponding NMR signals. Finally, amino acid residues in the C-terminal region of NS4A(1-48) from T33 to L48 show the smallest reduction in the free state peak intensities upon liposome addition (Figure 2A) . Inspection of HSQC spectra of mutant NS4A(1-48, L6E;M10E) in buffer and with increasing amounts of sonicated POPC liposomes revealed no changes in cross peak positions and only a minor Finally, amino acid residues in the C-terminal region of NS4A(1-48) from T33 to L48 show the smallest reduction in the free state peak intensities upon liposome addition (Figure 2A) . abstract: Dengue virus (DENV) is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A) is a vital component of the viral replication complex (RC) and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48) is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48) to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48) to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A. url: https://www.ncbi.nlm.nih.gov/pubmed/26197333/ doi: 10.3390/v7072812 id: cord-334560-1j9zmuub author: Hunt, Catherine L. title: Filovirus Entry: A Novelty in the Viral Fusion World date: 2012-02-07 words: 6445.0 sentences: 301.0 pages: flesch: 48.0 cache: ./cache/cord-334560-1j9zmuub.txt txt: ./txt/cord-334560-1j9zmuub.txt summary: Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. However, for reasons that are not entirely clear, this type of study has not been successful in identifying cell surface proteins that directly interact with EBOV GP to mediate virus entry [41, 42] . However, as both of these regions can be deleted from EBOV GP 1 without loss of viral transduction efficiency [16, [50] [51] [52] , it is likely that C-type lectins increase filovirus attachment to cells rather than serving as cellular receptors that mediate internalization of the virus into endosomes [53] . abstract: Ebolavirus (EBOV) and Marburgvirus (MARV) that compose the filovirus family of negative strand RNA viruses infect a broad range of mammalian cells. Recent studies indicate that cellular entry of this family of viruses requires a series of cellular protein interactions and molecular mechanisms, some of which are unique to filoviruses and others are commonly used by all viral glycoproteins. Details of this entry pathway are highlighted here. Virus entry into cells is initiated by the interaction of the viral glycoprotein(1) subunit (GP(1)) with both adherence factors and one or more receptors on the surface of host cells. On epithelial cells, we recently demonstrated that TIM-1 serves as a receptor for this family of viruses, but the cell surface receptors in other cell types remain unidentified. Upon receptor binding, the virus is internalized into endosomes primarily via macropinocytosis, but perhaps by other mechanisms as well. Within the acidified endosome, the heavily glycosylated GP(1) is cleaved to a smaller form by the low pH-dependent cellular proteases Cathepsin L and B, exposing residues in the receptor binding site (RBS). Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. Additional events such as further GP(1) processing and/or reducing events may also be required to generate a fusion-ready form of the glycoprotein. Once this has been achieved, sequences in the filovirus GP(2) subunit mediate viral/cellular membrane fusion via mechanisms similar to those previously described for other enveloped viruses. This multi-step entry pathway highlights the complex and highly orchestrated path of internalization and fusion that appears unique for filoviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/22470835/ doi: 10.3390/v4020258 id: cord-295044-eva0soja author: Hutson, Christina L. title: Monkeypox Virus Infections in Small Animal Models for Evaluation of Anti-Poxvirus Agents date: 2010-12-20 words: 4656.0 sentences: 223.0 pages: flesch: 52.0 cache: ./cache/cord-295044-eva0soja.txt txt: ./txt/cord-295044-eva0soja.txt summary: The disease pathogenesis has been conjectured and modeled largely from animal studies; initial models were using ectromelia infection of mice; some kinetic observations of virus shedding and viremia have been made in human studies of smallpox and monkeypox. challenged adult common squirrels (Sciurus vulgaris) with 10 6 pfu of MPXV Z-249 (Congo Basin clade) via IN, oral or scarification routes of infection [9] . A follow-up study found the LD 50 for the prairie dog MPXV model is approximately a hundred-times lower for the Congo Basin clade compared to the West African clade (5.9 × 10 3 and 1.29 × 10 5 , respectively) [15] , utilizing an IN route of infection. A prairie dog animal model of systemic orthopoxvirus disease using West African and Congo Basin strains of monkeypox virus Dosage comparison of Congo Basin and West African strains of monkeypox virus using a prairie dog animal model of systemic orthopoxvirus disease abstract: An ideal animal model for the study of a human disease is one which utilizes a route of infection that mimics the natural transmission of the pathogen; the ability to obtain disease with an infectious dose equivalent to that causing disease in humans; as well having a disease course, morbidity and mortality similar to that seen with human disease. Additionally, the animal model should have a mode(s) of transmission that mimics human cases. The development of small animal models for the study of monkeypox virus (MPXV) has been quite extensive for the relatively short period of time this pathogen has been known, although only a few of these models have been used to study anti-poxvirus agents. We will review those MPXV small animal models that have been developed thus far for the study of therapeutic agents. url: https://doi.org/10.3390/v2122763 doi: 10.3390/v2122763 id: cord-349117-xfir3m5p author: Hyseni, Inesa title: Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays date: 2020-09-10 words: 8298.0 sentences: 403.0 pages: flesch: 52.0 cache: ./cache/cord-349117-xfir3m5p.txt txt: ./txt/cord-349117-xfir3m5p.txt summary: After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study. SARS CoV-2 strain 2019-nCov/Italy wild-type virus (LV), which was handled in a level 3 bio-containment facility (BSL 3), was used as positive control in order to evaluate the spike glycoprotein expression, while a ∆-envelope pseudotype, prepared with the same procedure, was used as a negative control. To verify the expression of the spike protein in the SARS-CoV-2 pseudotypes, the spike was detected by Western blot; sera from convalescent SARS-CoV-2 patients, which have been shown to have a high neutralising titre in microneutralisation with a live virus, were used as the primary antibody, and goat anti-Human IgG as the secondary antibody. abstract: The recent outbreak of a novel Coronavirus (SARS-CoV-2) and its rapid spread across the continents has generated an urgent need for assays to detect the neutralising activity of human sera or human monoclonal antibodies against SARS-CoV-2 spike protein and to evaluate the serological immunity in humans. Since the accessibility of live virus microneutralisation (MN) assays with SARS-CoV-2 is limited and requires enhanced bio-containment, the approach based on “pseudotyping” can be considered a useful complement to other serological assays. After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study. The results obtained with pseudotype-based neutralisation assays mirrored those obtained when the same panel of sera was tested against the wild type virus, showing an evident convergence of the pseudotype-based neutralisation and MN results. The overall results lead to the conclusion that the pseudotype-based neutralisation assay is a valid alternative to using the wild-type strain, and although this system needs to be optimised and standardised, it can not only complement the classical serological methods, but also allows serological assessments to be made when other methods cannot be employed, especially in a human pandemic context. url: https://www.ncbi.nlm.nih.gov/pubmed/32927639/ doi: 10.3390/v12091011 id: cord-322206-roxa3ix6 author: I. Sardi, Silvia title: High-Quality Resolution of the Outbreak-Related Zika Virus Genome and Discovery of New Viruses Using Ion Torrent-Based Metatranscriptomics date: 2020-07-21 words: 4199.0 sentences: 212.0 pages: flesch: 46.0 cache: ./cache/cord-322206-roxa3ix6.txt txt: ./txt/cord-322206-roxa3ix6.txt summary: Herein, we used RNA-based metatranscriptomics associated with Ion Torrent deep sequencing to allow for the high-quality reconstitution of an outbreak-related Zika virus (ZIKV) genome (10,739 nt), with extended 5′-UTR and 3′-UTR regions, using a newly-implemented bioinformatics approach. Besides allowing for the assembly of one of the largest complete ZIKV genomes to date, our strategy also yielded high-quality complete genomes of two arthropod-infecting viruses co-infecting C6/36 cell lines, namely: Alphamesonivirus 1 strain Salvador (20,194 nt) and Aedes albopictus totivirus-like (4618 nt); the latter likely represents a new viral species. Altogether, our results demonstrate that our bioinformatics approach associated with Ion Torrent sequencing allows for the high-quality reconstruction of known and unknown viral genomes, overcoming the main limitation of RNA deep sequencing for virus identification. Here, we applied RNA-based metatranscriptomics associated with Ion Torrent deep sequencing and a newly developed Bioinformatics approach to the high-quality reconstitution of viral genomes. abstract: Arboviruses, including the Zika virus, have recently emerged as one of the most important threats to human health. The use of metagenomics-based approaches has already proven valuable to aid surveillance of arboviral infections, and the ability to reconstruct complete viral genomes from metatranscriptomics data is key to the development of new control strategies for these diseases. Herein, we used RNA-based metatranscriptomics associated with Ion Torrent deep sequencing to allow for the high-quality reconstitution of an outbreak-related Zika virus (ZIKV) genome (10,739 nt), with extended 5′-UTR and 3′-UTR regions, using a newly-implemented bioinformatics approach. Besides allowing for the assembly of one of the largest complete ZIKV genomes to date, our strategy also yielded high-quality complete genomes of two arthropod-infecting viruses co-infecting C6/36 cell lines, namely: Alphamesonivirus 1 strain Salvador (20,194 nt) and Aedes albopictus totivirus-like (4618 nt); the latter likely represents a new viral species. Altogether, our results demonstrate that our bioinformatics approach associated with Ion Torrent sequencing allows for the high-quality reconstruction of known and unknown viral genomes, overcoming the main limitation of RNA deep sequencing for virus identification. url: https://www.ncbi.nlm.nih.gov/pubmed/32708079/ doi: 10.3390/v12070782 id: cord-331094-22366b81 author: Ianevski, Aleksandr title: Potential Antiviral Options against SARS-CoV-2 Infection date: 2020-06-13 words: 6822.0 sentences: 424.0 pages: flesch: 49.0 cache: ./cache/cord-331094-22366b81.txt txt: ./txt/cord-331094-22366b81.txt summary: We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. After the initial screening, we identified apilimod, emetine, amodiaquine, obatoclax, homoharringtonine, salinomycin, arbidol, posaconazole and nelfinavir as compounds that rescued virus-infected cells from death (AUC from 285 to 585; Table S1 ). We next profiled transcriptional responses to nelfinavir, amodiaquine or both drugs in virus-or mock-infected Vero-E6 cells at 24 h. Anti-SARS-CoV-2 activity of safe-in man broad-spectrum antivirals in Vero-E6 cells. Here, we found that combinations of nelfinavir with salinomycin, amodiaquine, obatoclax, emetine or homoharringtonine were synergistic against SARS-CoV-2 in Vero-E6 cells. Thus, the amodiaquine and nelfinavir combination could result in better efficacy and decreased toxicity for the treatment of SARS-CoV-2 and perhaps other viral infections. Transcriptomic analysis of mock-and SARS-CoV-2-infected Vero-E6 cells treated with nelfinavir, amodiaquine or both drugs. abstract: As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32545799/ doi: 10.3390/v12060642 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-341968-uc8i9h0m author: Izaguirre, Gonzalo title: The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases date: 2019-09-09 words: 7870.0 sentences: 410.0 pages: flesch: 45.0 cache: ./cache/cord-341968-uc8i9h0m.txt txt: ./txt/cord-341968-uc8i9h0m.txt summary: A wide variety of viruses exploit furin and other proprotein convertases (PCs) of the constitutive protein secretion pathway in order to regulate their cell entry mechanism and infectivity. Like other enveloped viruses that rely on surface glycoproteins for binding and fusion, coronaviruses have the Spike (S) protein, which is cleaved by proteases during virion biosynthesis, as well as during entry into target cells [53] . The location of furin and related PCs in the vesicles of the constitutive protein secretion pathway, where viruses are assembled during morphogenesis or disassembled during cell entry, explains why a diversity of virus types have evolutionarily converged to depend on PCs. Viruses also use other types of proteases for the proteolytic regulation of the binding and fusion functions; however, proteases are restricted to specific cell types, which limits the range of the viral infection, so when some viruses mutate and acquire PC reactivity, they may expand their cell tropism and become more pathogenic. abstract: A wide variety of viruses exploit furin and other proprotein convertases (PCs) of the constitutive protein secretion pathway in order to regulate their cell entry mechanism and infectivity. Surface proteins of enveloped, as well as non-enveloped, viruses become processed by these proteases intracellularly during morphogenesis or extracellularly after egress and during entry in order to produce mature virions activated for infection. Although viruses also take advantage of other proteases, it is when some viruses become reactive with PCs that they may develop high pathogenicity. Besides reacting with furin, some viruses may also react with the PCs of the other specificity group constituted by PC4/PC5/PACE4/PC7. The targeting of PCs for inhibition may result in a useful strategy to treat infections with some highly pathogenic viruses. A wide variety of PC inhibitors have been developed and tested for their antiviral activity in cell-based assays. url: https://doi.org/10.3390/v11090837 doi: 10.3390/v11090837 id: cord-256370-cz88t29n author: Jansen van Vuren, Petrus title: Isolation of a Novel Fusogenic Orthoreovirus from Eucampsipoda africana Bat Flies in South Africa date: 2016-02-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We report on the isolation of a novel fusogenic orthoreovirus from bat flies (Eucampsipoda africana) associated with Egyptian fruit bats (Rousettus aegyptiacus) collected in South Africa. Complete sequences of the ten dsRNA genome segments of the virus, tentatively named Mahlapitsi virus (MAHLV), were determined. Phylogenetic analysis places this virus into a distinct clade with Baboon orthoreovirus, Bush viper reovirus and the bat-associated Broome virus. All genome segments of MAHLV contain a 5' terminal sequence (5'-GGUCA) that is unique to all currently described viruses of the genus. The smallest genome segment is bicistronic encoding for a 14 kDa protein similar to p14 membrane fusion protein of Bush viper reovirus and an 18 kDa protein similar to p16 non-structural protein of Baboon orthoreovirus. This is the first report on isolation of an orthoreovirus from an arthropod host associated with bats, and phylogenetic and sequence data suggests that MAHLV constitutes a new species within the Orthoreovirus genus. url: https://doi.org/10.3390/v8030065 doi: 10.3390/v8030065 id: cord-258323-vdeffy4l author: Jiang, Yuting title: Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV date: 2019-01-09 words: 4770.0 sentences: 253.0 pages: flesch: 48.0 cache: ./cache/cord-258323-vdeffy4l.txt txt: ./txt/cord-258323-vdeffy4l.txt summary: To detect expression of inflammasomes and complement components in MERS-CoV-infected THP-1 differentiated macrophages and hDPP4-Tg mice, 2 µg of total RNA from cells or the lung of mice we used as template for first-strand cDNA synthesis. IHC examination of CD68 and IFN-γ receptor expression also suggested greater macrophage infiltration and activation in the lung and spleen of mice at 7 days post-MERS-CoV infection ( Figure 3D ). IHC examination of CD68 and IFN-γ receptor expression also suggested greater macrophage infiltration and activation in the lung and spleen of mice at 7 days post-MERS-CoV infection ( Figure 3D ). These results suggest that complement inhibition decreased the expression of pyroptosis indicators, IL-1β and caspase-1, in mice infected with MERS-CoV. Here, our results showed that MERS-CoV infection induces pro-IL-1β transcription, and complement activation, which leads to pyroptosis in macrophages. Here, our results showed that MERS-CoV infection induces pro-IL-1β transcription, and complement activation, which leads to pyroptosis in macrophages. abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1β levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1β fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/30634407/ doi: 10.3390/v11010039 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: 8868.0 sentences: 441.0 pages: flesch: 52.0 cache: ./cache/cord-004334-y1fcw1dj.txt txt: ./txt/cord-004334-y1fcw1dj.txt summary: Antigen-specific IgG responses induced by immunization with the vaccine candidates were analyzed by enzyme-linked immunosorbent assay (ELISA) using purified soluble recombinant NiV glycoprotein G expressed in mammalian HEK293 cells. IFNAR−/− mice on a C57BL/6 background (MHC I = H2-Db/H2-Kb (H2-b) and MHC II = H2-IAb) were immunized twice with the MVA-NiVsG candidate vaccine via the intraperitoneal (i.p.) route, and splenocytes were prepared 8 days after the final inoculation, CD4 and CD8 T cells were purified and restimulated with overlapping 15mer peptides corresponding to the NiV-G protein. IFNAR−/− mice on a C57BL/6 background (MHC I = H2-Db/H2-Kb (H2-b) and MHC II = H2-IAb) were immunized twice with the MVA-NiVsG candidate vaccine via the intraperitoneal (i.p.) route, and splenocytes were prepared 8 days after the final inoculation, CD4 and CD8 T cells were purified and restimulated with overlapping 15mer peptides corresponding to the NiV-G protein. 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-351377-xorj8tnz author: Kao, Chi-Fei title: The Characterization of Immunoprotection Induced by a cDNA Clone Derived from the Attenuated Taiwan Porcine Epidemic Diarrhea Virus Pintung 52 Strain date: 2018-10-04 words: 5936.0 sentences: 234.0 pages: flesch: 48.0 cache: ./cache/cord-351377-xorj8tnz.txt txt: ./txt/cord-351377-xorj8tnz.txt summary: Moreover, inoculation with iPEDVPT-P96 elicited comparable levels of anti-PEDV specific plasma IgG and fecal/salivary IgA, neutralizing antibody titers, and similar but less effective immunoprotection against the virulent PEDVPT-P5 challenge compared to the parental PEDVPT-P96. In the present study, an infectious cDNA clone of an attenuated G2b PEDV strain was successfully generated for the first time, and the in vitro and in vivo data indicate that iPEDVPT-P96 is further attenuated but remains immunogenic compared to its parental PEDVPT-P96 viral stock. While one piglet in the PEDVPT-P96 group showed intermittent loose diarrhea (score = 1) and viral shedding at 6 to 11 days post-inoculation (DPI) with the peak viral titer of 1.45 ± 3.24 log 10 RNA copies/mL at 8 DPI (Figure 4) , no evidence of PEDV-associated clinical signs and fecal viral shedding were demonstrated in both iPEDVPT-P96 and mock groups. abstract: The porcine epidemic diarrhea virus (PEDV) poses a great threat to the global swine industries and the unreliable protection induced by the currently available vaccines remains a major challenge. We previously generated a genogroup 2b (G2b) PEDV Taiwan Pintung 52 (PEDVPT) strain, PEDVPT-P96, and determined its promising host immune response against the virulent PEDVPT-P5 strain. To study the attenuation determinants of PEDVPT-P96 and establish a PEDVPT-P96-based recombinant vector as a vaccine platform for further antigenicity modification, iPEDVPT-P96, a full-length cDNA clone of PEDVPT-P96, was established. Comparing to the parental PEDVPT-P96 virus, the iPEDVPT-P96 virus showed efficient replication kinetics with a delayed decline of viral load and similar but much more uniform plaque sizes in Vero cells. In the 5-week-old piglet model, fecal viral shedding was observed in the PEDVPT-P96-inoculated piglets, whereas those inoculated with iPEDVPT-P96 showed neither detectable fecal viral shedding nor PEDV-associated clinical signs. Moreover, inoculation with iPEDVPT-P96 elicited comparable levels of anti-PEDV specific plasma IgG and fecal/salivary IgA, neutralizing antibody titers, and similar but less effective immunoprotection against the virulent PEDVPT-P5 challenge compared to the parental PEDVPT-P96. In the present study, an infectious cDNA clone of an attenuated G2b PEDV strain was successfully generated for the first time, and the in vitro and in vivo data indicate that iPEDVPT-P96 is further attenuated but remains immunogenic compared to its parental PEDVPT-P96 viral stock. The successful development of the iPEDVPT-P96 cDNA clone could allow for the manipulation of the viral genome to study viral pathogenesis and facilitate the rapid development of effective vaccines. url: https://www.ncbi.nlm.nih.gov/pubmed/30287770/ doi: 10.3390/v10100543 id: cord-331414-i0oxm5mr author: Kautz, Tiffany F. title: A Low Fidelity Virus Shows Increased Recombination during the Removal of an Alphavirus Reporter Gene date: 2020-06-19 words: 5064.0 sentences: 241.0 pages: flesch: 45.0 cache: ./cache/cord-331414-i0oxm5mr.txt txt: ./txt/cord-331414-i0oxm5mr.txt summary: To examine this, GFP was inserted into TC-83, a live-attenuated vaccine for the alphavirus Venezuelan equine encephalitis virus, as well as a low-fidelity variant of TC-83, and passaged until fluorescence was no longer observed. To examine reporter gene stability, three independent replicates of TC-83 GFP and low-fidelity TC-83 GFP were passaged 10 times on Vero cells using an approximate MOI of 0.5 ( Figure 1A ). All three TC-83 GFP replicates contained deletion variants present at a low frequency that were able to selectively remove the GFP reporter gene by passage 10 (Figure 2A) . To better understand the mechanisms underlying the conserved removal of the low-fidelity TC-83 GFP gene, M-fold was used to determine the RNA secondary structure of the virus genome ( Figure 4C-E) . To characterize the role of RNA structure of the virus genome in RNA recombination site selection, we modeled the three most common deletions that occurred at high levels during low-fidelity TC-83 GFP passaging. abstract: Reporter genes for RNA viruses are well-known to be unstable due to putative RNA recombination events that excise inserted nucleic acids. RNA recombination has been demonstrated to be co-regulated with replication fidelity in alphaviruses, but it is unknown how recombination events at the minority variant level act, which is important for vaccine and trans-gene delivery design. Therefore, we sought to characterize the removal of a reporter gene by a low-fidelity alphavirus mutant over multiple replication cycles. To examine this, GFP was inserted into TC-83, a live-attenuated vaccine for the alphavirus Venezuelan equine encephalitis virus, as well as a low-fidelity variant of TC-83, and passaged until fluorescence was no longer observed. Short-read RNA sequencing using ClickSeq was performed to determine which regions of the viral genome underwent recombination and how this changed over multiple replication cycles. A rapid removal of the GFP gene was observed, where minority variants in the virus population accumulated small deletions that increased in size over the course of passaging. Eventually, these small deletions merged to fully remove the GFP gene. The removal was significantly enhanced during the passaging of low-fidelity TC-83, suggesting that increased levels of recombination are a defining characteristic of this mutant. url: https://www.ncbi.nlm.nih.gov/pubmed/32575413/ doi: 10.3390/v12060660 id: cord-003807-e2txo10z author: Ke, Fei title: Ranaviruses Bind Cells from Different Species through Interaction with Heparan Sulfate date: 2019-06-29 words: 5544.0 sentences: 300.0 pages: flesch: 54.0 cache: ./cache/cord-003807-e2txo10z.txt txt: ./txt/cord-003807-e2txo10z.txt summary: Here, viral cell-binding proteins and their cognate cellular receptors were investigated using two ranaviruses, Andrias davidianus ranavirus (ADRV) and Rana grylio virus (RGV), and two different cell lines, Chinese giant salamander thymus cells (GSTC) and Epithelioma papulosum cyprinid (EPC) cells. Furthermore, recombinant viral envelope proteins ADRV-58L and RGV-53R bound heparin-Sepharose beads implying the potential that cell surface HS is involved in the initial interaction between ranaviruses and susceptible host cells. Rana grylio virus (RGV) and Andrias davidianus ranavirus (ADRV) are ranaviruses isolated from diseased pig frogs R. Furthermore, since ranavirus viral envelope proteins [38] [39] [40] [45] [46] [47] [48] are likely involved in the initial interaction between virus and host, we examined the ability of RGV-53R and its ADRV homolog, ADVR-58L, to bind heparin-Sepharose beads. The effect of heparin on virus infection was tested by monitoring viral plaque formation following incubation of ADRV and RGV in the presence of increasing concentrations of heparin. abstract: Ranavirus cross-species infections have been documented, but the viral proteins involved in the interaction with cell receptors have not yet been identified. Here, viral cell-binding proteins and their cognate cellular receptors were investigated using two ranaviruses, Andrias davidianus ranavirus (ADRV) and Rana grylio virus (RGV), and two different cell lines, Chinese giant salamander thymus cells (GSTC) and Epithelioma papulosum cyprinid (EPC) cells. The heparan sulfate (HS) analog heparin inhibited plaque formation of ADRV and RGV in the two cell lines by more than 80% at a concentration of 5 μg/mL. In addition, enzymatic removal of cell surface HS by heparinase I markedly reduced plaque formation by both viruses and competition with heparin reduced virus-cell binding. These results indicate that cell surface HS is involved in ADRV and RGV cell binding and infection. Furthermore, recombinant viral envelope proteins ADRV-58L and RGV-53R bound heparin-Sepharose beads implying the potential that cell surface HS is involved in the initial interaction between ranaviruses and susceptible host cells. To our knowledge, this is the first report identifying cell surface HS as ranavirus binding factor and furthers understanding of interactions between ranaviruses and host cells. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669447/ doi: 10.3390/v11070593 id: cord-294347-axkdf5vu author: Kim, Shin-Hee title: Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines date: 2016-07-04 words: 7189.0 sentences: 353.0 pages: flesch: 44.0 cache: ./cache/cord-294347-axkdf5vu.txt txt: ./txt/cord-294347-axkdf5vu.txt summary: Specifically, vectored vaccines can have advantages for (i) viruses for which a live attenuated vaccine might not be feasible (i.e., HIV); (ii) viruses that do not grow well in vitro (i.e., human papillomavirus, hepatitis C virus, and norovirus); (iii) highly pathogenic viruses that present safety challenges during vaccine development (i.e., SARS-CoV and Ebola virus); (iv) viruses that lose infectivity due to physical instability (i.e., respiratory syncytial virus (RSV)); and (v) viruses that can exchange genes with circulating viruses (i.e., coronaviruses, influenza viruses, and enteroviruses) [4] . Further, immunized mice by the intravenous route were completely protected against a lethal dose of influenza virus, suggesting that NDV can be a safe and effective vaccine vector for possible use in mammalian and avian species. Immunization of primates with a Newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus abstract: Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens. url: https://doi.org/10.3390/v8070183 doi: 10.3390/v8070183 id: cord-310579-tnxokfwu author: Kim, Sung-Jae title: Molecular Characterization of Porcine Epidemic Diarrhea Virus and Its New Genetic Classification Based on the Nucleocapsid Gene date: 2020-07-23 words: 4887.0 sentences: 269.0 pages: flesch: 54.0 cache: ./cache/cord-310579-tnxokfwu.txt txt: ./txt/cord-310579-tnxokfwu.txt summary: title: Molecular Characterization of Porcine Epidemic Diarrhea Virus and Its New Genetic Classification Based on the Nucleocapsid Gene In the phylogenetic trees inferred from the D1-D2 datasets of the S gene ( Figure 2 , Supplementary Figures S1 and S2) , the PEDV strains were classified into five sub-genogroups (G1a, G1b, G2a, G2b, and G2c), which were previously designated [8] . In the phylogenetic trees inferred from the D1-D2 datasets of the S gene ( Figure 2 , Supplementary Figures S1 and S2) , the PEDV strains were classified into five sub-genogroups (G1a, G1b, G2a, G2b, and G2c), which were previously designated [8] . Supported by high posterior probability values (0.90-1), the phylogenetic trees inferred from the D3-D4 datasets of the N gene (Figure 3, Supplementary Figures S3 and S4) suggested that the classification of PEDV strains into four S gene-based sub-genogroups G1a, G1b, G2b, G2a/G2c was more reliable. Sequence and phylogenetic analysis of nucleocapsid genes of porcine epidemic diarrhea virus (PEDV) strains in China abstract: Porcine epidemic diarrhea virus (PEDV) causes continuous, significant damage to the swine industry worldwide. By RT-PCR-based methods, this study demonstrated the ongoing presence of PEDV in pigs of all ages in Korea at the average detection rate of 9.92%. By the application of Bayesian phylogenetic analysis, it was found that the nucleocapsid (N) gene of PEDV could evolve at similar rates to the spike (S) gene at the order of 10(−4) substitutions/site/year. Based on branching patterns of PEDV strains, three main N gene-base genogroups (N1, N2, and N3) and two sub-genogroups (N3a, N3b) were proposed in this study. By analyzing the antigenic index, possible antigenic differences also emerged in both the spike and nucleocapsid proteins between the three genogroups. The antigenic indexes of genogroup N3 strains were significantly lower compared with those of genogroups N1 and N2 strains in the B-cell epitope of the nucleocapsid protein. Similarly, significantly lower antigenic indexes in some parts of the B-cell epitope sequences of the spike protein (COE, S1D, and 2C10) were also identified. PEDV mutants derived from genetic mutations of the S and N genes may cause severe damage to swine farms by evading established host immunities. url: https://www.ncbi.nlm.nih.gov/pubmed/32717934/ doi: 10.3390/v12080790 id: cord-337707-xbwilp1w author: Kin, Nathalie title: Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes date: 2015-05-07 words: 5401.0 sentences: 275.0 pages: flesch: 56.0 cache: ./cache/cord-337707-xbwilp1w.txt txt: ./txt/cord-337707-xbwilp1w.txt summary: title: Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. Based on a bootscan analysis of the complete genome of the 3 HCoV-OC43s belonging to the circulating genotypes B, C, and D, it was assumed that a hot spot was likely located between the nsp12 and S genes, more precisely at the nsp12/nsp13 junction. This study focuses on the sequences of the nsp12, S, and N genes of 15 HCoV-OC43s detected in respiratory specimens sampled from 2001 to 2013. In this study, all HCoV-OC43s including the VR759 prototype strain are associated with three accession numbers in GenBank, for nsp12, S, and N genes ( Table 1 ). abstract: Human coronavirus OC43 (HCoV-OC43) is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome’s high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/26008694/ doi: 10.3390/v7052358 id: cord-285935-5rsk6g7l author: Kinast, Volker title: Hepatitis E Virus Drug Development date: 2019-05-28 words: 6638.0 sentences: 364.0 pages: flesch: 46.0 cache: ./cache/cord-285935-5rsk6g7l.txt txt: ./txt/cord-285935-5rsk6g7l.txt summary: Cyclic peptides (CP) that had been developed to abrogate interaction of p6Gag and TSG101 and inhibited viral release of HIV Virus like particles (VLPs) [76] were tested for their activity against HEV [77] . The compounds RBV and mycophenolic acid (MPA), both of which target enzymes involved in nucleotide synthesis, are either already used as treatment against HEV or have been reported for their potential to inhibit the virus. So far, the antiviral activity against HEV of only four drugs (Sofosbuvir, pegIFN-α, Ribavirin and silvestrol) was approved in experimental settings beyond in vitro cell culture systems. Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin Sofosbuvir shows antiviral activity in a patient with chronic hepatitis E virus infection Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo abstract: Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current therapy options are limited to the unspecific antivirals Ribavirin (RBV) and pegylated Interferon-α (pegIFN-α). RBV leads to viral clearance in only 80% of patients treated, and is, similar to pegIFN-α, contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development. We provide an overview of the current status of HEV antiviral research. Furthermore, we discuss strategies for drug development and the limitations of the approaches with respect to HEV. url: https://doi.org/10.3390/v11060485 doi: 10.3390/v11060485 id: cord-328042-e1is656g author: Klein, Steffen title: SARS-CoV-2 RNA Extraction Using Magnetic Beads for Rapid Large-Scale Testing by RT-qPCR and RT-LAMP date: 2020-08-07 words: 6328.0 sentences: 329.0 pages: flesch: 56.0 cache: ./cache/cord-328042-e1is656g.txt txt: ./txt/cord-328042-e1is656g.txt summary: The standard diagnostic pipeline for testing SARS-CoV-2 presence in patients with an ongoing infection is predominantly based on pharyngeal swabs, from which the viral RNA is extracted using commercial kits, followed by reverse transcription and quantitative PCR detection. Comparable viral RNA detection sensitivity and specificity were obtained by fluorescent and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) using a primer set targeting the N gene, as well as RT-qPCR using a primer set targeting the E gene, showing that the RNA extraction protocol presented here can be combined with a variety of detection methods at high throughput. Here, we show that the magnetic bead-based protocol yields RNA extracts comparable to the commercially available QIAcube viral RNA extraction kit, as determined by the commonly applied detection methods RT-qPCR and reverse transcription loop-mediated isothermal amplification (RT-LAMP) [16] . abstract: Rapid large-scale testing is essential for controlling the ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The standard diagnostic pipeline for testing SARS-CoV-2 presence in patients with an ongoing infection is predominantly based on pharyngeal swabs, from which the viral RNA is extracted using commercial kits, followed by reverse transcription and quantitative PCR detection. As a result of the large demand for testing, commercial RNA extraction kits may be limited and, alternatively, non-commercial protocols are needed. Here, we provide a magnetic bead RNA extraction protocol that is predominantly based on in-house made reagents and is performed in 96-well plates supporting large-scale testing. Magnetic bead RNA extraction was benchmarked against the commercial QIAcube extraction platform. Comparable viral RNA detection sensitivity and specificity were obtained by fluorescent and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) using a primer set targeting the N gene, as well as RT-qPCR using a primer set targeting the E gene, showing that the RNA extraction protocol presented here can be combined with a variety of detection methods at high throughput. Importantly, the presented diagnostic workflow can be quickly set up in a laboratory without access to an automated pipetting robot. url: https://doi.org/10.3390/v12080863 doi: 10.3390/v12080863 id: cord-347362-e4paw26n author: Klein-Richers, Ute title: Prevalence of Feline Coronavirus Shedding in German Catteries and Associated Risk Factors date: 2020-09-08 words: 4605.0 sentences: 216.0 pages: flesch: 50.0 cache: ./cache/cord-347362-e4paw26n.txt txt: ./txt/cord-347362-e4paw26n.txt summary: The aim of this prospective study was to determine prevalence and potential risk factors of feline coronavirus (FCoV) shedding. Four consecutive fecal samples of 179 cats from 37 German breeding catteries were analyzed for FCoV ribonucleic acid (RNA) by real-time reverse transcriptase polymerase chain reaction (RT-qPCR). Therefore, the aim of this study was to determine the prevalence of FCoV shedding in German breeding catteries and to evaluate associated risk factors. The number of cats per cattery, breed, hygiene management, husbandry conditions and outdoor access were not significantly associated with FCoV shedding in this population (Tables 4 and 5 ). Univariate risk factor analysis in the present study suggested that breed and the number of cats in the household had a significant influence on the prevalence of FCoV shedding, but these results have been distorted by the effect each breeder has on hygienic conditions and the risk of infection within their cattery. abstract: The aim of this prospective study was to determine prevalence and potential risk factors of feline coronavirus (FCoV) shedding. Four consecutive fecal samples of 179 cats from 37 German breeding catteries were analyzed for FCoV ribonucleic acid (RNA) by real-time reverse transcriptase polymerase chain reaction (RT-qPCR). Prevalence of shedding was calculated using different numbers of fecal samples per cat (1–4) and different sampling intervals (5–28 days). Information on potential risk factors for FCoV shedding was obtained by a questionnaire. Risk factor analysis was performed using a generalized linear mixed model (GLMM). Most cats (137/179, 76.5%, 95% confidence interval (CI) 69.8–82.2) shed FCoV at least at once. None of the tested 37 catteries was free of FCoV. Prevalence calculated including all four (76.5%, 95% CI 69.8–82.2) or the last three (73.7%, 95% CI 66.8–79.7) samples per cat was significantly higher than the prevalence calculated with only the last sample (61.5%, 95% CI 54.2–68.3; p = 0.0029 and 0.0175, respectively). Young age was significantly associated with FCoV shedding while the other factors were not. For identification of FCoV shedders in multi-cat households, at least three fecal samples per cat should be analyzed. Young age is the most important risk factor for FCoV shedding. url: https://www.ncbi.nlm.nih.gov/pubmed/32911718/ doi: 10.3390/v12091000 id: cord-349560-8n65rgfz author: Kleines, Michael title: WU Polyomavirus (WUPyV): A Recently Detected Virus Causing Respiratory Disease? date: 2009-11-04 words: 4053.0 sentences: 230.0 pages: flesch: 45.0 cache: ./cache/cord-349560-8n65rgfz.txt txt: ./txt/cord-349560-8n65rgfz.txt summary: The WU polyomavirus (WUPyV) is a novel member of the family Polyomaviridae recently detected in respiratory tract specimens by shotgun sequencing. Creer and co-workers [1] identified at least one potential pathogen in 69% of specimens from adults suffering from lower respiratory tract infections (LRTI, 63% contained viruses, 26% contained bacteria) still leaving a significant diagnostic gap to be filled with so far unidentified pathogenic microorganisms. For this reason, detection of virus-specific antibodies by complement fixation assays, enzyme linked immunosorbent assays (ELISA), or immunofluorescence assays (IFA), all of which are available for established respiratory viruses, is inappropriate for the identification of the etiologic agent causing an acute respiratory tract infection, but useful for retrospective or epidemiological studies. Following the discovery of WUPyV in Australia, the virus was detected in specimens from patients with respiratory tract disease on all continents suggesting a worldwide distribution [10, [29] [30] [31] . abstract: The WU polyomavirus (WUPyV) is a novel member of the family Polyomaviridae recently detected in respiratory tract specimens by shotgun sequencing. Intriguingly, viral genome has been detected in 0.4% to 11.5% of respiratory tract specimens from children with respiratory disease. The levels of co-infection with established respiratory viruses were in the range between 30.8% and 91.7%. Moreover, some studies report detection of WUPyV in stool or serum. So far, WUPyV infections can not be distinguished from other viral infections by means of clinical symptoms. Respiratory tract disease like pneumonia or bronchitis is frequently observed in patients harbouring WUPyV. Detection of viremia suggests systemic infections. However, the available data do not prove WUPyV to be a human pathogen. Further investigations are necessary. url: https://doi.org/10.3390/v1030678 doi: 10.3390/v1030678 id: cord-354738-4rxradwz author: Kohl, Claudia title: European Bats as Carriers of Viruses with Zoonotic Potential date: 2014-08-13 words: 4797.0 sentences: 289.0 pages: flesch: 52.0 cache: ./cache/cord-354738-4rxradwz.txt txt: ./txt/cord-354738-4rxradwz.txt summary: In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. Various publications reviewed bats globally as carriers and potential reservoir hosts of human-pathogenic and zoonotic viruses [3] [4] [5] [6] [7] [8] [9] [10] , while hardly anything is known about human-pathogenicity of European bat viruses apart from lyssaviruses. Similar to the case of the LLOV filovirus, virus isolates and prevalence studies in both humans and bats could improve knowledge and clarify their zoonotic potential. Sero-prevalence studies should be conducted on the orthoreoviruses isolated from European bats, especially as a closely related virus was detected in a diseased child in Slovenia [83] . Other bat viruses detected by using molecular techniques should be isolated (e.g., MERS-like CoV or Bat Bunyavirus) to allow for characterization and follow-up sero-prevalence studies. abstract: Bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies virus, and coronaviruses). While numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in European bats. Although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are conducted. At present, it is assumed that the risk posed by bats to the general public is rather low. In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. All European bat species and their roosts are legally protected and some European species are even endangered. Nevertheless, the increasing public fear of bats and their viruses is an obstacle to their protection. Educating the public regarding bat lyssaviruses might result in reduced threats to both the public and the bats. url: https://www.ncbi.nlm.nih.gov/pubmed/25123684/ doi: 10.3390/v6083110 id: cord-317037-1qydcc5e author: Kumar, Asit title: Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention date: 2020-08-13 words: 9406.0 sentences: 511.0 pages: flesch: 37.0 cache: ./cache/cord-317037-1qydcc5e.txt txt: ./txt/cord-317037-1qydcc5e.txt summary: Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from the plasma membrane. HIV-infected U1 macrophages upon Cigarette smoke condensate (CSC) treatment enhanced the packaging of IL-6 in EVs; IL-8 served as a biomarker for HIV patients with altered immune function due to alcohol and tobacco abuse [20, 116, 117] Host protein APOBEC3G Inhibit replication of viral infectivity factor (vif) -deficient and wild-type HIV-1 in recipient cells [118] miRNA vmiR-88 and vmiR-99 Hepatocytes secreted exosomes participate in virus replication [142] Viral miRNAs HBV-miR-3 Represses viral protein production and HBV replication [143] HTLV-1 Viral proteins gp61, Tax, and HBZ Increase cell-to-cell contact and promote a potential increase in viral spread [144] Zika Viral genetic material and protein RNA and ZIKV-E EVs derived from Infected C6/36 cells promote infection and activation of monocytes with enhanced TNF-α mRNA expression. abstract: Extracellular vesicles (EVs) have shown their potential as a carrier of molecular information, and they have been involved in physiological functions and diseases caused by viral infections. Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from the plasma membrane. They are released via a direct outward budding and fission of plasma membrane blebs into the extracellular space to either facilitate virus propagation or regulate the immune responses. Moreover, EVs generated by virus-infected cells can incorporate virulence factors including viral protein and viral genetic material, and thus can resemble noninfectious viruses. Interactions of EVs with recipient cells have been shown to activate signaling pathways that may contribute to a sustained cellular response towards viral infections. EVs, by utilizing a complex set of cargos, can play a regulatory role in viral infection, both by facilitating and suppressing the infection. EV-based antiviral and antiretroviral drug delivery approaches provide an opportunity for targeted drug delivery. In this review, we summarize the literature on EVs, their associated involvement in transmission in viral infections, and potential therapeutic implications. url: https://doi.org/10.3390/v12080887 doi: 10.3390/v12080887 id: cord-003772-1345qct4 author: Kummer, Susann title: IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells date: 2019-06-12 words: 7843.0 sentences: 417.0 pages: flesch: 45.0 cache: ./cache/cord-003772-1345qct4.txt txt: ./txt/cord-003772-1345qct4.txt summary: title: IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells To determine whether an IAV-induced viral membrane fusion and genome uncoating are required for the observed IFITM3 signal increase upon IAV infection, we performed experiments in the presence of Bafilomycin A1, specifically inhibiting endosomal acidification, or in the presence of Amantadine, specifically blocking the tetrameric M2 channel of IAV, thereby preventing genome uncoating. To determine whether an IAV-induced viral membrane fusion and genome uncoating are required for the observed IFITM3 signal increase upon IAV infection, we performed experiments in the presence of Bafilomycin A1, specifically inhibiting endosomal acidification, or in the presence of Amantadine, specifically blocking the tetrameric M2 channel of IAV, thereby preventing genome uncoating. A strong IFITM3 clustering with a ring-like appearance indicating vesicle coating was observed in both IAV-infected A549 cells ( Figure 5A ) and HSAEpCs at 10 h p.i. abstract: Interferon-induced transmembrane proteins (IFITMs) have been shown to strongly affect influenza A virus (IAV) infectivity in tissue culture. Moreover, polymorphisms in IFITM3 have been associated with the severity of the disease in humans. IFITM3 appears to act early in the infection, but its mechanism of action and potential interactions with incoming IAV structures are not yet defined. Here, we visualized endogenous IFITM3 interactions with IAV in the human lung epithelial cell line A549 and in primary human airway epithelial cells employing stimulated emission depletion super-resolution microscopy. By applying an iterative approach for the cluster definition and computational cluster analysis, we found that IFITM3 reorganizes into clusters as IAV infection progresses. IFITM3 cluster formation started at 2-3 h post infection and increased over time to finally coat IAV-containing endosomal vesicles. This IAV-induced phenotype was due to the endosomal recruitment of IFITM3 rather than to an overall increase in the IFITM3 abundance. While the IAV-induced IFITM3 clustering and localization to endosomal vesicles was comparable in primary human airway epithelial cells and the human lung epithelial cell line A549, the endogenous IFITM3 signal was higher in primary cells. Moreover, we observed IFITM3 signals adjacent to IAV-containing recycling endosomes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631848/ doi: 10.3390/v11060548 id: cord-272018-txdc0c3j author: Laing, Eric D. title: Enhanced Autophagy Contributes to Reduced Viral Infection in Black Flying Fox Cells date: 2019-03-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bats are increasingly implicated as hosts of highly pathogenic viruses. The underlying virus–host interactions and cellular mechanisms that promote co-existence remain ill-defined, but physiological traits such as flight and longevity are proposed to drive these adaptations. Autophagy is a cellular homeostatic process that regulates ageing, metabolism, and intrinsic immune defense. We quantified basal and stimulated autophagic responses in black flying fox cells, and demonstrated that although black flying fox cells are susceptible to Australian bat lyssavirus (ABLV) infection, viral replication is dampened in these bat cells. Black flying fox cells tolerated prolonged ABLV infection with less cell death relative to comparable human cells, suggesting post-entry mechanisms interference with virus replication. An elevated basal autophagic level was observed and autophagy was induced in response to high virus doses. Pharmacological stimulation of the autophagy pathway reduced virus replication, indicating autophagy acts as an anti-viral mechanism. Enhancement of basal and virus-induced autophagy in bat cells connects related reports that long-lived species possess homeostatic processes that dampen oxidative stress and macromolecule damage. Exemplifying the potential that evolved cellular homeostatic adaptations like autophagy may secondarily act as anti-viral mechanisms, enabling bats to serve as natural hosts to an assortment of pathogenic viruses. Furthermore, our data suggest autophagy-inducing drugs may provide a novel therapeutic strategy for combating lyssavirus infection. url: https://doi.org/10.3390/v11030260 doi: 10.3390/v11030260 id: cord-003917-bswndfvk author: Lalle, Eleonora title: Pulmonary Involvement during the Ebola Virus Disease date: 2019-08-24 words: 5545.0 sentences: 245.0 pages: flesch: 40.0 cache: ./cache/cord-003917-bswndfvk.txt txt: ./txt/cord-003917-bswndfvk.txt summary: Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . Interestingly, evidence collected in animal studies, in the epidemiological analysis of transmission chains, and in the most recent Ebola outbreaks suggests that EBOV may be able to cause primary pulmonary infection. abstract: Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. EVD is associated with pathologies in several organs, including the liver, kidney, and lung. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, little is known about lung pathogenesis and the controversial issue of aerosol transmission in EVD. This review highlights the pulmonary involvement in EVD, with a special focus on the new data emerging from the 2013–2016 Ebola outbreak. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784166/ doi: 10.3390/v11090780 id: cord-297339-et2305rz author: Lauber, Chris title: Genetics-Based Classification of Filoviruses Calls for Expanded Sampling of Genomic Sequences date: 2012-08-31 words: 4480.0 sentences: 235.0 pages: flesch: 46.0 cache: ./cache/cord-297339-et2305rz.txt txt: ./txt/cord-297339-et2305rz.txt summary: In DEmARC, virus clusters are delimited objectively by devising a universal family-wide threshold on intra-cluster genetic divergence of viruses that is specific for each level of the classification. Based on our experience with other virus families, we conclude that the current sampling of filovirus genomic sequences needs to be considerably expanded in order to resolve these uncertainties in the framework of genetics-based classification. The DEmARC specifics include (i) the use of pairwise evolutionary distances (PEDs) instead of uncorrected p-distances, and (ii) a quantitative method to devise taxon levels and associated PED thresholds for virus clustering in a systematic and family-wide manner. The first selected threshold (PED of 0.120) results in seven clusters ( Figure 1B ) that match the official or tentative ICTV species of the family Filoviridae. In the high-sampling case of picornaviruses, no PED values with zero frequency are observed which suggests that the current sampling of filovirus genome sequences may strongly underestimate the natural genetic diversity in the family. abstract: We have recently developed a computational approach for hierarchical, genome-based classification of viruses of a family (DEmARC). In DEmARC, virus clusters are delimited objectively by devising a universal family-wide threshold on intra-cluster genetic divergence of viruses that is specific for each level of the classification. Here, we apply DEmARC to a set of 56 filoviruses with complete genome sequences and compare the resulting classification to the ICTV taxonomy of the family Filoviridae. We find in total six candidate taxon levels two of which correspond to the species and genus ranks of the family. At these two levels, the six filovirus species and two genera officially recognized by ICTV, as well as a seventh tentative species for Lloviu virus and prototyping a third genus, are reproduced. DEmARC lends the highest possible support for these two as well as the four other levels, implying that the actual number of valid taxon levels remains uncertain and the choice of levels for filovirus species and genera is arbitrary. Based on our experience with other virus families, we conclude that the current sampling of filovirus genomic sequences needs to be considerably expanded in order to resolve these uncertainties in the framework of genetics-based classification. url: https://www.ncbi.nlm.nih.gov/pubmed/23170166/ doi: 10.3390/v4091425 id: cord-003775-1axsebya author: Lelli, Davide title: Hypsugopoxvirus: A Novel Poxvirus Isolated from Hypsugo savii in Italy date: 2019-06-19 words: 3010.0 sentences: 152.0 pages: flesch: 45.0 cache: ./cache/cord-003775-1axsebya.txt txt: ./txt/cord-003775-1axsebya.txt summary: Herein, we report the isolation, nearly complete genome sequencing, and annotation of a novel poxvirus detected from an insectivorous bat (Hypsugo savii) in Northern Italy. In this study, we report the isolation, nearly complete genomic sequencing, and annotation of a novel poxvirus detected from an insectivorous bat (Hypsugo savii) in Northern Italy. Phylogenetic analyses suggest that HYPV belongs to the Chordopoxvirinae subfamily, revealing the highest similarity (85%) with Eptesipoxvirus (EPTV) detected from the microbat Eptesicus fuscus in WA, USA in 2011, which is associated with bat necrosuppurative osteomyelitis in multiple joints. For the nearly complete viral genome sequencing, BLAST analysis revealed the highest nucleotide identity (85%) to the Eptesipoxvirus (EPTV) strain "Washington", a member of the Chordopoxvirinae subfamily identified in microbats in the USA ( Table 2 ). To conclude, a new poxvirus, HYPV, was detected in bats in Europe and its viral ecology and disease associations should be investigated further. abstract: Interest in bat-related viruses has increased considerably during the last decade, leading to the discovery of a rising number of new viruses in several bat species. Poxviridae are a large, diverse family of DNA viruses that can infect a wide range of vertebrates and invertebrates. To date, only a few documented detections of poxviruses have been described in bat populations on three different continents (America, Africa, and Australia). These viruses are phylogenetically dissimilar and have diverse clinical impacts on their hosts. Herein, we report the isolation, nearly complete genome sequencing, and annotation of a novel poxvirus detected from an insectivorous bat (Hypsugo savii) in Northern Italy. The virus is tentatively named Hypsugopoxvirus (HYPV) after the bat species from which it was isolated. The nearly complete genome size is 166,600 nt and it encodes 161 genes. Genome analyses suggest that HYPV belongs to the Chordopoxvirinae subfamily, with the highest nucleotide identity (85%) to Eptesipoxvirus (EPTV) detected from a microbat Eptesicus fuscus in WA, USA, in 2011. To date, HYPV represents the first poxvirus detected in bats in Europe; thus, its viral ecology and disease associations should be investigated further. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631891/ doi: 10.3390/v11060568 id: cord-338811-2bi2edcw author: Lennemann, Nicholas J. title: Imaging-Based Reporter Systems to Define CVB-Induced Membrane Remodeling in Living Cells date: 2020-09-25 words: 6671.0 sentences: 327.0 pages: flesch: 43.0 cache: ./cache/cord-338811-2bi2edcw.txt txt: ./txt/cord-338811-2bi2edcw.txt summary: To define the dynamic process of enterovirus membrane remodeling of major secretory pathway organelles, we have developed plasmid-based reporter systems that utilize viral protease-dependent release of a nuclear-localized fluorescent protein from the endoplasmic reticulum (ER) membrane during infection, while retaining organelle-specific fluorescent protein markers such as the ER and Golgi. To monitor enterovirus infection in real-time, we adapted cell-based reporter methodologies previously used for flaviviruses and hepatitis C virus that rely on viral protease cleavage-dependent translocation of a membrane-anchored cytoplasmic fluorescent proteins to the nucleus [27] [28] [29] . CVB infection of RepER expressing U2OS cells resulted in a clear translocation of GFP-NLS reporter to the nucleus and eventual dispersal due to cell lysis, while the mCherry-KDEL was maintained in the membranous structure of the ER (Video S1 and Figure 2a) . Live-cell imaging of CVB infected cells expressing these reporters allowed for the real-time visualization of virus-induced changes to the host cell, including the collapse of the peripheral ER network and loss of Golgi integrity. abstract: Enteroviruses manipulate host membranes to form replication organelles, which concentrate viral and host factors to allow for efficient replication. However, this process has not been well-studied in living cells throughout the course of infection. To define the dynamic process of enterovirus membrane remodeling of major secretory pathway organelles, we have developed plasmid-based reporter systems that utilize viral protease-dependent release of a nuclear-localized fluorescent protein from the endoplasmic reticulum (ER) membrane during infection, while retaining organelle-specific fluorescent protein markers such as the ER and Golgi. This system thus allows for the monitoring of organelle-specific changes induced by infection in real-time. Using long-term time-lapse imaging of living cells infected with coxsackievirus B3 (CVB), we detected reporter translocation to the nucleus beginning ~4 h post-infection, which correlated with a loss of Golgi integrity and a collapse of the peripheral ER. Lastly, we applied our system to study the effects of a calcium channel inhibitor, 2APB, on virus-induced manipulation of host membranes. We found that 2APB treatment had no effect on the kinetics of infection or the percentage of infected cells. However, we observed aberrant ER structures in CVB-infected cells treated with 2APB and a significant decrease in viral-dependent cell lysis, which corresponded with a decrease in extracellular virus titers. Thus, our system provides a tractable platform to monitor the effects of inhibitors, gene silencing, and/or gene editing on viral manipulation of host membranes, which can help determine the mechanism of action for antivirals. url: https://doi.org/10.3390/v12101074 doi: 10.3390/v12101074 id: cord-000808-pxryt8wn author: Leroy, Eric title: Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa date: 2012-09-13 words: 2871.0 sentences: 133.0 pages: flesch: 38.0 cache: ./cache/cord-000808-pxryt8wn.txt txt: ./txt/cord-000808-pxryt8wn.txt summary: Since the reemergence of Ebola virus in Central Africa, the CIRMF "Emerging Viral Disease Unit" developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the National Public Health System and the World Health Organization to epidemics of Ebola virus disease. As a National reference laboratory, CIRMF has the following roles: diagnosis of suspected cases during outbreaks of viral hemorrhagic fevers or severe clinical infectious syndromes; development of new methods for diagnosing such infections; surveillance of animal fatalities in reservoir or intermediate hosts; and intervention during outbreaks of unknown etiology. The Emerging Viral Diseases Unit, CIRMF, proposes forming a research partnership to study infectious diseases transmitted by animals of the tropical rain forests regions of Equatorial Africa. abstract: Health research programs targeting the population of Gabon and Equatorial Africa at the International Center for Medical Research in Franceville (CIRMF), Gabon, have evolved during the years since its inception in 1979 in accordance with emerging diseases. Since the reemergence of Ebola virus in Central Africa, the CIRMF “Emerging Viral Disease Unit” developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the National Public Health System and the World Health Organization to epidemics of Ebola virus disease. The Unit carries out a unique investigation program on the natural history of the filoviruses, emergence of epidemics, and Ebola virus pathogenesis. In addition, academic training is provided at all levels to regional and international students covering emerging conditions (host factors, molecular biology, genetics) that favor the spread of viral diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499821/ doi: 10.3390/v4091592 id: cord-323585-iv2dcpqj author: Li, Su title: eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus date: 2015-08-10 words: 6142.0 sentences: 343.0 pages: flesch: 59.0 cache: ./cache/cord-323585-iv2dcpqj.txt txt: ./txt/cord-323585-iv2dcpqj.txt summary: The NS5A protein of classical swine fever virus (CSFV) is involved in the RNA synthesis and viral replication. The GST or GST-NS5A fusion proteins expressed in Escherichia coli BL21(DE3) were purified with glutathione Sepharose 4B resin and incubated with the lysate of HEK293T cells overexpressing the Myc-tagged eEF1A. The immunoprecipitate was analyzed by Western blotting using the anti-Flag MAb (1:1000) and a rabbit anti-Myc PAb (1:500); (D) Co-IP analysis of eEF1A and NS5A by the anti-Myc MAb. HEK293T cells were cotransfected with the indicated plasmids (+) or empty vectors (''), the cell lysate was collected at 48 h post-transfection (hpt), incubated with the anti-Myc MAb and Protein G-Agarose. The bound proteins were analyzed by immunoblotting using the anti-Myc monoclonal antibody (MAb) (1:1000); (B) eEF1A interacts with the CSFV IRES in a dose-dependent manner. The bound proteins were analyzed by immunoblotting using the anti-Myc monoclonal antibody (MAb) (1:1000); (B) eEF1A interacts with the CSFV IRES in a dose-dependent manner. abstract: The NS5A protein of classical swine fever virus (CSFV) is involved in the RNA synthesis and viral replication. However, the NS5A-interacting cellular proteins engaged in the CSFV replication are poorly defined. Using yeast two-hybrid screen, the eukaryotic elongation factor 1A (eEF1A) was identified to be an NS5A-binding partner. The NS5A–eEF1A interaction was confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pulldown and laser confocal microscopy assays. The domain I of eEF1A was shown to be critical for the NS5A–eEF1A interaction. Overexpression of eEF1A suppressed the CSFV growth markedly, and conversely, knockdown of eEF1A enhanced the CSFV replication significantly. Furthermore, eEF1A, as well as NS5A, was found to reduce the translation efficiency of the internal ribosome entry site (IRES) of CSFV in a dose-dependent manner, as demonstrated by luciferase reporter assay. Streptavidin pulldown assay revealed that eEF1A could bind to the CSFV IRES. Collectively, our results suggest that eEF1A interacts with NS5A and negatively regulates the growth of CSFV. url: https://www.ncbi.nlm.nih.gov/pubmed/26266418/ doi: 10.3390/v7082833 id: cord-267709-i2loz1xb author: Li, Tongya title: Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200 date: 2019-05-09 words: 6910.0 sentences: 387.0 pages: flesch: 51.0 cache: ./cache/cord-267709-i2loz1xb.txt txt: ./txt/cord-267709-i2loz1xb.txt summary: title: Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200 Finally, the antiviral effects of IFITM1 on cell proliferation and HBV replication were found to be partially restored when HBc was co-transfected with BAF200. Finally, our data demonstrates that the antiviral effects of IFITM1 on cellular proliferation and HBV replication are partially restored when HBc is co-expressed with BAF200 in HBV-infected cells. First, BAF200C was co-transfected with either empty vectors or HBc into 293T cells, then the whole cell lysate was immunoprecipitated by an anti-Flag antibody and then subjected to western blot by anti-HA antibodies to detect the interacting proteins. (d) HepG2 cells were co-transfected with the pGC-FU-Flag-BAF200 and pCMV-HA vectors or pCMV-HA-HBc, and co-IP assays were carried out with anti-HA antibody or IgG. We co-transfected HBc and BAF200 into HepG2 cells, treated the cells with 500 U/mL IFNα, and detected the expression of IFITM1 by western blot (Figure 2d ). abstract: Human hepatitis B virus core protein (HBc) is a structural protein of the hepatitis B virus (HBV) and contributes to HBV regulation of host-cell transcription. However, the mechanisms of transcriptional regulation remain poorly characterized. To dissect the function of HBc, a yeast two-hybrid was performed to identify HBc-binding proteins, and the C-terminal of BRG1/hBRM-associated factors 200 (BAF200C) was identified. Then, the existence of HBc interactions with BAF200C and full-length BAF200 was confirmed via co-immunoprecipitation assays in 293T, HepG2 and HepG2-NTCP cells. Furthermore, we show that the binding between HBc and BAF200 was of vital importance to HBc mediated downregulation of interferon-induced transmembrane protein 1 (IFITM1) expression, and the mechanisms for the downregulation were disclosed as follows. Basal level of IFITM1 expression depends on BAF200, rather than the JAK–STAT1 pathway. The interaction of HBc with BAF200 disturbs the stability of the polybromo-associated BAF (PBAF) complex and results in the suppression of IFTM1 transcription. Finally, the antiviral effects of IFITM1 on cell proliferation and HBV replication were found to be partially restored when HBc was co-transfected with BAF200. Collectively, our findings indicate that HBc plays a role in HBV resistance against the antiviral activities of IFNα, providing details about HBV evasion of host innate immunity. url: https://doi.org/10.3390/v11050427 doi: 10.3390/v11050427 id: cord-288556-o8i6j3b2 author: Li, Yanpeng title: Virome of a Feline Outbreak of Diarrhea and Vomiting Includes Bocaviruses and a Novel Chapparvovirus date: 2020-05-04 words: 5872.0 sentences: 325.0 pages: flesch: 53.0 cache: ./cache/cord-288556-o8i6j3b2.txt txt: ./txt/cord-288556-o8i6j3b2.txt summary: We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and identified three different feline bocaviruses shed by 9/17 cats. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease. Here, we analyzed a multi-facility outbreak of vomiting and diarrhea in cats using the following approaches: a commercial feline diarrhea panel of PCR tests for known enteric pathogens; viral metagenomics; and follow-up PCRs. Multiple mammalian viruses of varied origins were detected. DNA was extracted from each individual fecal sample (and one pool of 3, cat#973-975) shown in Table 3 plus 4 vomit samples using the QIAamp MinElute Virus Spin Kit (Qiagen, Hilden, Germany), and PCR assays were used for the detection of different viral nucleic acids in each sample. abstract: An unexplained outbreak of feline diarrhea and vomiting, negative for common enteric viral and bacterial pathogens, was subjected to viral metagenomics and PCR. We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and identified three different feline bocaviruses shed by 9/17 cats. Also detected were nucleic acids from attenuated vaccine viruses, members of the normal feline virome, viruses found in only one or two cases, and viruses likely derived from ingested food products. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32375386/ doi: 10.3390/v12050506 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-002076-7t4d4vvo author: Li, Yongfeng title: Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology date: 2016-05-06 words: 4996.0 sentences: 229.0 pages: flesch: 36.0 cache: ./cache/cord-002076-7t4d4vvo.txt txt: ./txt/cord-002076-7t4d4vvo.txt summary: Commonly used tests based on wild-type viruses, such as immunostaining, cannot meet the demands for rapid detection of viral replication, high-throughput screening for antivirals, as well as for tracking viral proteins or virus transport in real time. This article reviews the applications of RCREVs in diagnostic and molecular virology, including rapid neutralization tests, high-throughput screening systems, identification of viral receptors and virus-host interactions, dynamics of viral infections in vitro and in vivo, vaccination approaches and others. Replicating-competent reporter-expressing viruses (RCREVs) are one type of artificially modified viruses that not only retain the viral genetic characteristics but also possess the new properties of the reporter genes, which represent a useful tool for quantitative analysis of viral replication and tracking viral protein transport in both living cells and animals. abstract: Commonly used tests based on wild-type viruses, such as immunostaining, cannot meet the demands for rapid detection of viral replication, high-throughput screening for antivirals, as well as for tracking viral proteins or virus transport in real time. Notably, the development of replicating-competent reporter-expressing viruses (RCREVs) has provided an excellent option to detect directly viral replication without the use of secondary labeling, which represents a significant advance in virology. This article reviews the applications of RCREVs in diagnostic and molecular virology, including rapid neutralization tests, high-throughput screening systems, identification of viral receptors and virus-host interactions, dynamics of viral infections in vitro and in vivo, vaccination approaches and others. However, there remain various challenges associated with RCREVs, including pathogenicity alterations due to the insertion of a reporter gene, instability or loss of the reporter gene expression, or attenuation of reporter signals in vivo. Despite all these limitations, RCREVs have become powerful tools for both basic and applied virology with the development of new technologies for generating RCREVs, the inventions of novel reporters and the better understanding of regulation of viral replication. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885082/ doi: 10.3390/v8050127 id: cord-003761-ikni2acz author: Li, Zengbin title: Biological Function and Application of Picornaviral 2B Protein: A New Target for Antiviral Drug Development date: 2019-06-04 words: 6425.0 sentences: 331.0 pages: flesch: 39.0 cache: ./cache/cord-003761-ikni2acz.txt txt: ./txt/cord-003761-ikni2acz.txt summary: In this review, we mainly summarize recent research data on the viroporin or viroporin-like activity of 2B proteins, which affects the biological function of the membrane, regulates cell death, and affects the host immune response. In particular, the 2B protein may change the Ca 2+ concentration to regulate autophagy and apoptosiswhich are distinct cell death mechanisms controlled by the virus to effectively evade the host immunity, thereby promoting viral replication and release [48] [49] [50] [51] [52] . Thus, the main points of focus for research on the structure and function of the 2B protein toward ultimate drug development are: (1) mechanism of increasing membrane permeability to disturb the ion balance, (2) regulation of autophagy and apoptosis, (3) inhibition of the host immune response, and (4) promotion of viral replication and release. abstract: Picornaviruses are associated with acute and chronic diseases. The clinical manifestations of infections are often mild, but infections may also lead to respiratory symptoms, gastroenteritis, myocarditis, meningitis, hepatitis, and poliomyelitis, with serious impacts on human health and economic losses in animal husbandry. Thus far, research on picornaviruses has mainly focused on structural proteins such as VP1, whereas the non-structural protein 2B, which plays vital roles in the life cycle of the viruses and exhibits a viroporin or viroporin-like activity, has been overlooked. Viroporins are viral proteins containing at least one amphipathic α-helical structure, which oligomerizes to form transmembrane hydrophilic pores. In this review, we mainly summarize recent research data on the viroporin or viroporin-like activity of 2B proteins, which affects the biological function of the membrane, regulates cell death, and affects the host immune response. Considering these mechanisms, the potential application of the 2B protein as a candidate target for antiviral drug development is discussed, along with research challenges and prospects toward realizing a novel treatment strategy for picornavirus infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630369/ doi: 10.3390/v11060510 id: cord-342923-prgorr3d author: Li, Zhonghua title: Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication date: 2018-03-13 words: 4170.0 sentences: 266.0 pages: flesch: 56.0 cache: ./cache/cord-342923-prgorr3d.txt txt: ./txt/cord-342923-prgorr3d.txt summary: title: Cellular hnRNP A1 Interacts with Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus and Impairs Viral Replication Replication of PEDV was inhibited by silencing the expression of hnRNP A1 in CCL-81 cells, suggesting the positive effect of hnRNP A1 on PEDV infection. Previous studies have demonstrated hnRNP A1 could interact with N proteins of SARS Coronavirus and mouse hepatitis virus (MHV) [14, 19] . Our previous work has proved that hnRNP A1 underwent different regulations in jejunum tissues of piglets infected with PEDV virulent strain and its attenuated strain [20] . The beads were then washed with IP lysis buffer five times and boiled in sample buffer, and the proteins were subjected to SDS-PAGE, followed by immunoblotting analysis with anti-Flag PAb or anti-hnRNP A1 PAb. CCL-81 cells grown on coverslips were infected with PEDV YN144 strain, YN13 strain and CV777 strain, respectively, at a multiplicity of infection (MOI) 0.001. abstract: The nucleocapsid (N) protein is a major structural component of porcine epidemic diarrhea virus (PEDV), which is predicted to be a multifunctional protein in viral replication. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a cellular protein participating in the splicing of pre-mRNA in the nucleus and translation regulation in the cytoplasm. According to our previous proteomic study about PEDV infection in vivo, hnRNP A1 was thought to be a cellular factor influencing PEDV replication. In this report, PEDV N protein was discovered to colocalize with cellular hnRNP A1 in perinuclear region of PEDV infected cells. Co-immunoprecipitation (CO-IP) results clearly demonstrated that PEDV N protein could bind to human hnRNP A1. Replication of PEDV was inhibited by silencing the expression of hnRNP A1 in CCL-81 cells, suggesting the positive effect of hnRNP A1 on PEDV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/29534017/ doi: 10.3390/v10030127 id: cord-003130-p2h8p5bm author: Lindqvist, Richard title: Tick-Borne Flaviviruses and the Type I Interferon Response date: 2018-06-21 words: 8350.0 sentences: 481.0 pages: flesch: 48.0 cache: ./cache/cord-003130-p2h8p5bm.txt txt: ./txt/cord-003130-p2h8p5bm.txt summary: There are more than 70 viruses in the genus flavivirus, and they are transmitted by arthropods such as mosquitoes (dengue virus (DENV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), yellow fever virus (YFV), and Zika virus (ZIKV) and ticks (tick-borne encephalitis virus (TBEV), Langat virus (LGTV), Kyasanur forest disease virus (KFDV), Omsk hemorrhagic fever virus (OHFV), Powassan virus (POWV), and Louping-ill virus (LIV)) [1] [2] [3] [4] [5] . Two other ISGs which have been shown to be antivirally active against TBEV are virus inhibitory protein endoplasmic reticulum associated interferon inducible (viperin) and tripartite motif-79α (TRIM79α). The role of interferon in tick-borne encephalitis virus-infected l cells. A functional toll-like receptor 3 gene (tlr3) may be a risk factor for tick-borne encephalitis virus (tbev) infection Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection 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-257665-12gyrmh2 author: Liu, Shan-Lu title: Emerging Viruses without Borders: The Wuhan Coronavirus date: 2020-01-22 words: 790.0 sentences: 48.0 pages: flesch: 56.0 cache: ./cache/cord-257665-12gyrmh2.txt txt: ./txt/cord-257665-12gyrmh2.txt summary: We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists, but we also believe that increased transparency on disease reporting and data sharing with international colleagues are crucial for curbing the spread of this newly emerging virus to other parts of the world. We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists, but we also believe that increased transparency on disease reporting and data sharing with international colleagues are crucial for curbing the spread of this newly emerging virus to other parts of the world. We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists [3] , as this represents an important first step in curbing the spread of the new virus to other parts of the world. abstract: The recently emerged coronavirus in Wuhan, China has claimed at least six lives as of January 22 and infected hundreds if not thousands of individuals. The situation has drawn international attention, including from the virology community. We applaud the rapid release to the public of the genome sequence of the new virus by Chinese virologists, but we also believe that increased transparency on disease reporting and data sharing with international colleagues are crucial for curbing the spread of this newly emerging virus to other parts of the world. url: https://doi.org/10.3390/v12020130 doi: 10.3390/v12020130 id: cord-004022-cr0zskcw author: Lu, Chien-Yi title: The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles date: 2019-10-31 words: 5532.0 sentences: 235.0 pages: flesch: 48.0 cache: ./cache/cord-004022-cr0zskcw.txt txt: ./txt/cord-004022-cr0zskcw.txt summary: The packaging cells carrying the recombinant plasmid encoding the viral structural proteins are transfected with DNA-launched replicons and then self-replicate viral subgenomes and express all viral proteins, allowing viral assembly and release as SRIPs. Several flavivirus, replicon-based SRIPs, including JEV, dengue virus, West Nile virus, and tick-borne encephalitis virus have been generated and demonstrated as safer vaccine candidates [15] [16] [17] . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) . To examine the production of ZIKV Natal RGN SRIPs, the supernatant of replicon-transfected packaging cells was harvested 72 h post-transfection and analyzed using dot-blotting, real-time RT-PCR, and TCID50 assays (Figure 4) . abstract: Zika virus (ZIKV) is transmitted by Aedes mosquitoes and exhibits genetic variation with African and Asian lineages. ZIKV Natal RGN strain, an Asian-lineage virus, has been identified in brain tissues from fetal autopsy cases with microcephaly and is suggested to be a neurotropic variant. However, ZIKV Natal RGN strain has not been isolated; its biological features are not yet illustrated. This study rescued and characterized recombinant, single-round infectious particles (SRIPs) of the ZIKV Natal RGN strain using reverse genetic and synthetic biology techniques. The DNA-launched replicon of ZIKV Natal RGN was constructed and contains the EGFP reporter, lacks prM-E genes, and replicates under CMV promoter control. The peak in the ZIKV Natal RGN SRIP titer reached 6.25 × 10(6) TCID50/mL in the supernatant of prM-E-expressing packaging cells 72 h post-transfection with a ZIKV Natal RGN replicon. The infectivity of ZIKV Natal RGN SRIPs has been demonstrated to correlate with the green florescence intensity of the EGFP reporter, the SRIP-induced cytopathic effect, and ZIKV’s non-structural protein expression. Moreover, ZIKV Natal RGN SRIPs effectively self-replicated in rhabdomyosarcoma/muscle, glioblastoma/astrocytoma, and retinal pigmented epithelial cells, displaying unique cell susceptibility with differential attachment activity. Therefore, the recombinant ZIKV Natal RGN strain was rescued as SRIPs that could be used to elucidate the biological features of a neurotropic strain regarding cell tropism and pathogenic components, apply for antiviral agent screening, and develop vaccine candidates. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893733/ doi: 10.3390/v11111005 id: cord-332576-pd62s65y author: Lu, Chien-Yi title: Single-Round Infectious Particle Antiviral Screening Assays for the Japanese Encephalitis Virus date: 2017-04-10 words: 7343.0 sentences: 352.0 pages: flesch: 46.0 cache: ./cache/cord-332576-pd62s65y.txt txt: ./txt/cord-332576-pd62s65y.txt summary: This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins. The expression of EGFP and viral proteins as well as the synthesis of positive-and negative-sense RNA subgenomes in MJ-47-reated infected cells were determined using fluorescent microscope, immunofluorescent staining and real-time RT-PCR assays, as described above. Real-time RT-PCR and immunofluorescent staining demonstrated JEV-EGFP replicon-driven viral positive-and negative-sense RNA genomes were synthesized, as well as replicon-driven EGFP and viral non-structural proteins being expressed in the packaging cell line (Figures 3 and 4) . Real-time RT-PCR and immunofluorescent staining demonstrated JEV-EGFP replicon-driven viral positive-and negative-sense RNA genomes were synthesized, as well as replicon-driven EGFP and viral non-structural proteins being expressed in the packaging cell line (Figures 3 and 4) . abstract: Japanese Encephalitis virus (JEV) is a mosquito-borne flavivirus with a positive-sense single-stranded RNA genome that contains a big open reading frame (ORF) flanked by 5′- and 3′- untranslated regions (UTRs). Nearly 30,000 JE cases with 10,000 deaths are still annually reported in East Asia. Although the JEV genotype III vaccine has been licensed, it elicits a lower protection against other genotypes. Moreover, no effective treatment for a JE case is developed. This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins. Genetic instability of JEV genome cDNA in the pBR322 plasmid was associated with the prokaryotic promoter at 5′ end of the JEV genome that triggers the expression of the structural proteins in E. coli. JEV structural proteins were toxic E. coli, thus the encoding region for structural proteins was replaced by a reporter gene (enhanced green fluorescent protein, EGFP) that was in-frame fused with the first eight amino acids of the C protein at N-terminus and the foot-and-mouth disease virus (FMDV) 2A peptide at C-terminus in a pBR322-based JEV-EGFP replicon. JEV-EGFP SRIPs generated from JEV-EGFP replicon-transfected packaging cells displayed the infectivity with cytopathic effect induction, self-replication of viral genomes, and the expression of EGFP and viral proteins. Moreover, the combination of JEV-EGFP SRIP plus flow cytometry was used to determine the half maximal inhibitory concentration (IC50) values of antiviral agents according to fluorescent intensity and positivity of SRIP-infected packaging cells post treatment. MJ-47, a quinazolinone derivative, significantly inhibited JEV-induced cytopathic effect, reducing the replication and expression of JEV-EGFP replicon in vitro. The IC50 value of 6.28 µM for MJ-47 against JEV was determined by the assay of JEV-EGFP SRIP infection in packaging cells plus flow cytometry that was more sensitive, effective, and efficient compared to the traditional plaque assay. Therefore, the system of JEV-EGFP SRIPs plus flow cytometry was a rapid and reliable platform for screening antiviral agents and evaluating antiviral potency. url: https://doi.org/10.3390/v9040076 doi: 10.3390/v9040076 id: cord-313161-07iwwsfz author: Lundstrom, Kenneth title: Alphavirus-Based Vaccines date: 2014-06-16 words: 6844.0 sentences: 322.0 pages: flesch: 30.0 cache: ./cache/cord-313161-07iwwsfz.txt txt: ./txt/cord-313161-07iwwsfz.txt summary: Furthermore, sequential immunization with SIN and VEE replicon particles expressing the type 1 HIV gp140 envelope (Env) and trimeric Env protein in MF59 adjuvant provided partial protection in macaques against intravenous challenges with high doses of simian-human immunodeficiency virus (SHIV) [61] . In another study, chimeric VEE/SIN replicon particles were applied for the expression of measles virus hemagglutinin (H) and fusion (F) proteins, which elicited high-titer neutralizing antibody and IFNɤ-producing T-cells in macaques after intradermal vaccination [48] . Furthermore, vaccination with recombinant particles expressing the P1A gene [105] and the human papilloma virus (HPV) E7 gene [89] from SFV and VEE vectors, respectively, provided protection against further tumor development in mice. When TRAMP mice were prophylactically immunized with a prostate stem cell antigen (PSCA) DNA plasmid followed by VEE-PSCA particle administration, a specific immune response and anti-tumor protection were observed in 90% of vaccinated animals [102] . abstract: Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans. url: https://doi.org/10.3390/v6062392 doi: 10.3390/v6062392 id: cord-003646-kjkuet78 author: López-Camacho, César title: Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus date: 2019-04-03 words: 6359.0 sentences: 314.0 pages: flesch: 49.0 cache: ./cache/cord-003646-kjkuet78.txt txt: ./txt/cord-003646-kjkuet78.txt summary: We have designed viral-vectored vaccines to express the structural proteins of CHIKV, using the replication-deficient chimpanzee adenoviral platform, ChAdOx1. Our vaccines induce high frequencies of anti-chikungunya specific T-cell responses as well as high titres of anti-CHIKV E2 antibodies with high capacity for in vitro neutralisation. In mice, ChAdOx1 vaccines candidates expressing sCHIKV antigens are able to induce strong humoral and cellular responses upon a single and non-adjuvanted immunisation approach. Finally, whilst durability of humoral responses was achieved upon a single immunisation, MVA vaccines expressing sCHIKV were produced to be used as an alternative heterologous booster regime (ChAdOx1/MVA), in order to increase neutralising antibody titres. In addition, a western blot was performed using a monoclonal antibody against CHIKV E1 (Figure 3d ); we detected a specific band in the positive control E1 protein (lane 9), as well as a 55 kDa band in all the supernatant fractions from both ChAdOx1 sCHIKV-and ChAdOx1 sCHIKV ∆C-transduced cells. abstract: Chikungunya virus (CHIKV) has caused extensive outbreaks in several countries within the Americas, Asia, Oceanic/Pacific Islands, and Europe. In humans, CHIKV infections cause a debilitating disease with acute febrile illness and long-term polyarthralgia. Acute and chronic symptoms impose a major economic burden to health systems and contribute to poverty in affected countries. An efficacious vaccine would be an important step towards decreasing the disease burden caused by CHIKV infection. Despite no licensed vaccine is yet available for CHIKV, there is strong evidence of effective asymptomatic viral clearance due to neutralising antibodies against the viral structural proteins. We have designed viral-vectored vaccines to express the structural proteins of CHIKV, using the replication-deficient chimpanzee adenoviral platform, ChAdOx1. Expression of the CHIKV antigens results in the formation of chikungunya virus-like particles. Our vaccines induce high frequencies of anti-chikungunya specific T-cell responses as well as high titres of anti-CHIKV E2 antibodies with high capacity for in vitro neutralisation. Our results indicate the potential for further clinical development of the ChAdOx1 vaccine platform in CHIKV vaccinology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521086/ doi: 10.3390/v11040322 id: cord-305857-2409me0p author: López-Roig, Marc title: Seroprevalence Dynamics of European Bat Lyssavirus Type 1 in a Multispecies Bat Colony date: 2014-09-04 words: 3873.0 sentences: 207.0 pages: flesch: 49.0 cache: ./cache/cord-305857-2409me0p.txt txt: ./txt/cord-305857-2409me0p.txt summary: In recent years, bats have been implicated in numerous emerging infectious disease events and have been recognized as important reservoir hosts for viruses that can cross the species barrier to infect humans and other domestic and wild mammals [3] . Persistent viral infections occurring among long-lived bats, coupled with their often gregarious roosting behavior, could greatly increase the potential for intra-and inter-species transmission of viruses [7] , especially in summer and winter periods. To study the variation in EBLV-1-antibody prevalence, we conducted two analyses: first, three explanatory variables (sex, species and year) were first screened using a univariate analysis and a chi-square test to check for statistically significant associations with serological status (0: negative; 1: positive). We report the results of the prevalence of specific EBLV-1 neutralizing antibody analysis from the 2004-2012 period in nine bat species roosting in the same refuge. abstract: We report an active surveillance study of the occurrence of specific antibodies to European Bat Lyssavirus Type 1 (EBLV-1) in bat species, scarcely studied hitherto, that share the same refuge. From 2004 to 2012, 406 sera were obtained from nine bat species. Blood samples were subjected to a modified fluorescent antibody virus neutralization test to determine the antibody titer. EBLV-1-neutralizing antibodies were detected in six of the nine species analyzed (Pipistrellus pipistrellus, P. kuhlii, Hypsugo savii, Plecotus austriacus, Eptesicus serotinus and Tadarida teniotis). Among all bats sampled, female seroprevalence (20.21%, 95% CI: 14.78%–26.57%) was not significantly higher than the seroprevalence in males (15.02%, 95% CI: 10.51%–20.54%). The results showed that the inter-annual variation in the number of seropositive bats in T. teniotis and P. austriacus showed a peak in 2007 (>70% of EBLV-1 prevalence). However, significant differences were observed in the temporal patterns of the seroprevalence modeling of T. teniotis and P. austriacus. The behavioral ecology of these species involved could explain the different annual fluctuations in EBLV-1 seroprevalence. url: https://doi.org/10.3390/v6093386 doi: 10.3390/v6093386 id: cord-256924-c7ftvgio author: Mackay, Ian M. title: Co-circulation of Four Human Coronaviruses (HCoVs) in Queensland Children with Acute Respiratory Tract Illnesses in 2004 date: 2012-04-23 words: 4409.0 sentences: 236.0 pages: flesch: 49.0 cache: ./cache/cord-256924-c7ftvgio.txt txt: ./txt/cord-256924-c7ftvgio.txt summary: Positive specimens were used to develop novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. Severity scores were similar to those from a random selection of young children who were positive for respiratory syncytial virus at a different time but from the same specimen population. Recently three new HCoVs, all detected in patients with ARIs were described; the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, HCoV-NL63 in 2004 and HCoV-HKU1 in 2005 [16] [17] [18] . Our retrospective study also observed that clinical features and the average severity scores from patients with HCoV were very close to those from a similarly aged set of children who were positive for HRSV. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method Frequent detection of human coronaviruses in clinical specimens from patients with respiratory tract infection by use of a novel real-time reverse-transcription polymerase chain reaction abstract: Acute respiratory illnesses (ARIs) with unconfirmed infectious aetiologies peak at different times of the year. Molecular diagnostic assays reduce the number of unconfirmed ARIs compared to serology- or culture-based techniques. Screening of 888 inpatient and outpatient respiratory specimens spanning late autumn through to early spring, 2004, identified the presence of a human coronavirus (HCoV) on 74 occasions (8.3% of all specimens and 26.3% of all respiratory virus detections). Prevalence peaked in August (late winter in the southern hemisphere) when they were detected in 21.9% of specimens tested. HCoV-HKU1 and HCoV-OC43 comprised 82.4% of all HCoVs detected. Positive specimens were used to develop novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. An objective clinical severity score was assigned to each positive HCoV patient. Severity scores were similar to those from a random selection of young children who were positive for respiratory syncytial virus at a different time but from the same specimen population. During the cooler months of 2004, sensitive and specific RT-rtPCRs identified the concurrent circulation of all four HCoVs, a quarter of which co-occurred with another virus and most of which were from children under the age of two years. url: https://doi.org/10.3390/v4040637 doi: 10.3390/v4040637 id: cord-325823-bt7xo9iq author: Magassouba, N’Faly title: A Sporadic and Lethal Lassa Fever Case in Forest Guinea, 2019 date: 2020-09-23 words: 3342.0 sentences: 190.0 pages: flesch: 62.0 cache: ./cache/cord-325823-bt7xo9iq.txt txt: ./txt/cord-325823-bt7xo9iq.txt summary: In January 2019, a 35-year-old man, a wood merchant from Kissidougou, Forest Guinea, presented himself at several health centers with persistent fever, frequent vomiting and joint pain. Due to the similarity of symptoms with malaria, Lassa fever is still a disease that is difficult to recognize and that may remain undiagnosed in health centers in Guinea. However, Guinea has very few reported acute human cases, and only a few studies have a posteriori described acute Lassa fever cases in the prefectures of Kindia, Faranah, Kissidougou, Guekedou, Macenta and N''Zérékoré in 1992 and 1996-1999 [12] [13] [14] . A total of 41 individuals in contact with the case in Kissidougou (n = 7), Mamou (n = 32) and Conakry (n = 2) were identified by the field teams, and further sampled for LASV RT-PCR as per Ministry of Health National Strategy guidelines in the case of VHF suspicion even in the absence of symptoms. abstract: Lassa fever is a rodent-borne disease caused by Lassa virus (LASV). It causes fever, dizziness, vertigo, fatigue, coughing, diarrhea, internal bleeding and facial edema. The disease has been known in Guinea since 1960 but only anectodical acute cases have been reported to date. In January 2019, a 35-year-old man, a wood merchant from Kissidougou, Forest Guinea, presented himself at several health centers with persistent fever, frequent vomiting and joint pain. He was repeatedly treated for severe malaria, and died three weeks later in Mamou regional hospital. Differential diagnosis identified LASV as the cause of death. No secondary cases were reported. The complete LASV genome was obtained using next-generation sequencing. Phylogenetic analysis showed that this strain, namely the Kissidougou strain, belongs to the clade IV circulating in Guinea and Sierra Leone, and is thought to have emerged some 150 years ago. Due to the similarity of symptoms with malaria, Lassa fever is still a disease that is difficult to recognize and that may remain undiagnosed in health centers in Guinea. url: https://doi.org/10.3390/v12101062 doi: 10.3390/v12101062 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-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: nan sentences: nan pages: flesch: nan cache: txt: summary: 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-286343-s8n1ldol author: Martin, Javier title: Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic date: 2020-10-09 words: 5925.0 sentences: 340.0 pages: flesch: 53.0 cache: ./cache/cord-286343-s8n1ldol.txt txt: ./txt/cord-286343-s8n1ldol.txt summary: We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations. However, it was clear that there was a large reduction of SARS-CoV-2 RNA concentration in sewage between 14th April and 12th May. Positive and negative results were independently confirmed using a second real-time PCR platform (Stratagene 3000P) in a different NIBSC laboratory. However, it was clear that there was a large reduction of SARS-CoV-2 RNA concentration in sewage between 14th April and 12th May. Positive and negative results were independently confirmed using a second real-time PCR platform (Stratagene 3000P) in a different NIBSC laboratory (data not shown). abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the ongoing coronavirus disease (COVID-19) pandemic, is frequently shed in faeces during infection, and viral RNA has recently been detected in sewage in some countries. We have investigated the presence of SARS-CoV-2 RNA in wastewater samples from South-East England between 14th January and 12th May 2020. A novel nested RT-PCR approach targeting five different regions of the viral genome improved the sensitivity of RT-qPCR assays and generated nucleotide sequences at sites with known sequence polymorphisms among SARS-CoV-2 isolates. We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. Low levels of viral RNA were detected in a sample from 11th February, 3 days before the first case was reported in the sewage plant catchment area. SARS-CoV-2 RNA concentration increased in March and April, and a sharp reduction was observed in May, showing the effects of lockdown measures. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations. url: https://www.ncbi.nlm.nih.gov/pubmed/33050264/ doi: 10.3390/v12101144 id: cord-263315-g7os15m1 author: Martins-da-Silva, Andrea title: Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response date: 2018-01-18 words: 6975.0 sentences: 460.0 pages: flesch: 48.0 cache: ./cache/cord-263315-g7os15m1.txt txt: ./txt/cord-263315-g7os15m1.txt summary: title: Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response The two most abundant secreted peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an interferon-inducible protein that mediates antiviral activity, and forskolin-binding protein (FKBP), a member of the immunophilin family, which mediates the effect of immunosuppressive drugs. In human and mouse plasmacytoid dendritic cells (pDCs), which are professional interferon-producing cells specialized in recognizing viral RNA and DNA through the endosomal Toll-like receptors (TLRs) TLR7 and TLR9, respectively, PLSCR1 was described as a TLR9-binding protein that plays a significant role in type-1 interferon responses in pDCs by regulating TLR9 expression and trafficking [57] . Binding of FKBP51 to TRAF proteins facilitates the type-I interferon response induced by dsRNA transfection or Newcastle disease virus (NDV) infection in murine fibroblasts. Binding of FKBP51 to TRAF proteins facilitates the type-I interferon response induced by dsRNA transfection or Newcastle disease virus (NDV) infection in murine fibroblasts. abstract: Hematophagous insects transmit infectious diseases. Sand flies are vectors of leishmaniasis, but can also transmit viruses. We have been studying immune responses of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in the Americas. We identified a non-specific antiviral response in L. longipalpis LL5 embryonic cells when treated with non-specific double-stranded RNAs (dsRNAs). This response is reminiscent of interferon response in mammals. We are investigating putative effectors for this antiviral response. Secreted molecules have been implicated in immune responses, including interferon-related responses. We conducted a mass spectrometry analysis of conditioned medium from LL5 cells 24 and 48 h after dsRNA or mock treatment. We identified 304 proteins. At 24 h, 19 proteins had an abundance equal or greater than 2-fold change, while the levels of 17 proteins were reduced when compared to control cells. At the 48 h time point, these numbers were 33 and 71, respectively. The two most abundant secreted peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an interferon-inducible protein that mediates antiviral activity, and forskolin-binding protein (FKBP), a member of the immunophilin family, which mediates the effect of immunosuppressive drugs. The transcription profile of most candidates did not follow the pattern of secreted protein abundance. url: https://www.ncbi.nlm.nih.gov/pubmed/29346269/ doi: 10.3390/v10010043 id: cord-263699-gosqpg3k author: Martínez, José L. title: Role of the Guanine Nucleotide Exchange Factor GBF1 in the Replication of RNA Viruses date: 2020-06-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The guanine nucleotide exchange factor GBF1 is a well-known factor that can activate different ADP-ribosylation factor (Arf) proteins during the regulation of different cellular vesicular transport processes. In the last decade, it has become increasingly evident that GBF1 can also regulate different steps of the replication cycle of RNA viruses belonging to different virus families. GBF1 has been shown not only to facilitate the intracellular traffic of different viral and cellular elements during infection, but also to modulate the replication of viral RNA, the formation and maturation of viral replication complexes, and the processing of viral proteins through mechanisms that do not depend on its canonical role in intracellular transport. Here, we review the various roles that GBF1 plays during the replication of different RNA viruses. url: https://doi.org/10.3390/v12060682 doi: 10.3390/v12060682 id: cord-292948-1n5ej08f author: Masse, Shirley title: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014–2020) in France date: 2020-06-10 words: 3875.0 sentences: 209.0 pages: flesch: 54.0 cache: ./cache/cord-292948-1n5ej08f.txt txt: ./txt/cord-292948-1n5ej08f.txt summary: title: Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014–2020) in France Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs. Coronaviruses (CoVs) are an enveloped, single positive-strand RNA species of viruses belonging to the Coronaviridae family, which infect birds and mammals. Here, we document the epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) observed in general practice. To study the weekly number of HCoVs detected among ILI/ARI patients seen in general practice during the six influenza seasons, we gathered all samples collected by GPs for influenza surveillance and for the IRIIS study (Table 1 and Figure 1 ). abstract: There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14–15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0–14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs. url: https://doi.org/10.3390/v12060630 doi: 10.3390/v12060630 id: cord-312272-g4n426cm author: Matczuk, Anna Karolina title: Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells date: 2019-08-09 words: 8453.0 sentences: 375.0 pages: flesch: 53.0 cache: ./cache/cord-312272-g4n426cm.txt txt: ./txt/cord-312272-g4n426cm.txt summary: title: Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells To determine whether these results were caused by the emergence of viruses containing mutations, the intracellular RNA was isolated after infection with P7, P10, P15, and P19 EAVGp3-HA virus and subjected to RT-PCR, followed by sequence analysis ( Figure 2C ). To determine whether these results were caused by the emergence of viruses containing mutations, the intracellular RNA was isolated after infection with P7, P10, P15, and P19 EAVGp3-HA virus and subjected to RT-PCR, followed by sequence analysis ( Figure 2C ). We studied the co-localization of the Gp3-HA, E protein, and N protein in EAV-infected BHK-21 cells using immunofluorescence microscopy (18 h p.i.). The tagged Gp3 in the virus context might facilitate research on the biology of EAV, e.g., in this study, we analyzed the localization of the Gp3-HA in the infected cells. abstract: Equine arteritis virus (EAV) is a prototype member of the Arterivirus family, comprising important pathogens of domestic animals. Minor glycoproteins of Arteriviruses are responsible for virus entry and cellular tropism. The experimental methods for studying minor Arterivirus proteins are limited because of the lack of antibodies and nested open reading frames (ORFs). In this study, we generated recombinant EAV with separated ORFs 3 and 4, and Gp3 carrying HA-tag (Gp3-HA). The recombinant viruses were stable on passaging and replicated in titers similar to the wild-type EAV. Gp3-HA was incorporated into the virion particles as monomers and as a Gp2/Gp3-HA/Gp4 trimer. Gp3-HA localized in ER and, to a lesser extent, in the Golgi, it also co-localized with the E protein but not with the N protein. The co-localization of Gp3-HA and the E protein with ERGIC was reduced. Moreover, EAV with Gp3-HA could become a valuable research tool for identifying host cell factors during infection and the role of Gp3 in virus attachment and entry. url: https://doi.org/10.3390/v11080735 doi: 10.3390/v11080735 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-321013-8pkrg0mx author: McBride, Ruth title: The Coronavirus Nucleocapsid Is a Multifunctional Protein date: 2014-08-07 words: 10761.0 sentences: 476.0 pages: flesch: 44.0 cache: ./cache/cord-321013-8pkrg0mx.txt txt: ./txt/cord-321013-8pkrg0mx.txt summary: The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. The M protein is the main core shell component and a 16 amino acid domain (aa 237-252) on the CTD of M protein binds directly to N protein via an ionic interaction, leading to specific genome encapsidation in the budding viral particle [81] [82] [83] .The N protein therefore plays an essential structural role in the CoV virion through a network of interactions with (i) the genomic RNA; (ii) M protein and (iii) other N proteins. Amino acid residues critical for RNA-binding in the N-terminal domain of the nucleocapsid protein are essential determinants for the infectivity of coronavirus in cultured cells Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA abstract: The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. Recent studies have confirmed that N is a multifunctional protein. The aim of this review is to highlight the properties and functions of the N protein, with specific reference to (i) the topology; (ii) the intracellular localization and (iii) the functions of the protein. url: https://doi.org/10.3390/v6082991 doi: 10.3390/v6082991 id: cord-315164-nidgnvvi author: Medkour, Hacène title: Adenovirus Infections in African Humans and Wild Non-Human Primates: Great Diversity and Cross-Species Transmission date: 2020-06-18 words: 6818.0 sentences: 359.0 pages: flesch: 58.0 cache: ./cache/cord-315164-nidgnvvi.txt txt: ./txt/cord-315164-nidgnvvi.txt summary: Non-human primates (NHPs) are known hosts for adenoviruses (AdVs), so there is the possibility of the zoonotic or cross-species transmission of AdVs. As with humans, AdV infections in animals can cause diseases that range from asymptomatic to fatal. The aim of this study was to investigate the occurrence and diversity of AdVs in: (i) fecal samples of apes and monkeys from different African countries (Republic of Congo, Senegal, Djibouti and Algeria), (ii) stool of humans living near gorillas in the Republic of Congo, in order to explore the potential zoonotic risks. Samples were screened by real-time and standard PCRs, followed by the sequencing of the partial DNA polymerase gene in order to identify the AdV species. In the present study, we sought to investigate the presence and molecular diversity of AdVs in wild African NHPs, including great apes (gorillas and chimpanzees), macaques and other monkeys (baboons, green monkeys), living in close proximity to or outside human settlements. abstract: Non-human primates (NHPs) are known hosts for adenoviruses (AdVs), so there is the possibility of the zoonotic or cross-species transmission of AdVs. As with humans, AdV infections in animals can cause diseases that range from asymptomatic to fatal. The aim of this study was to investigate the occurrence and diversity of AdVs in: (i) fecal samples of apes and monkeys from different African countries (Republic of Congo, Senegal, Djibouti and Algeria), (ii) stool of humans living near gorillas in the Republic of Congo, in order to explore the potential zoonotic risks. Samples were screened by real-time and standard PCRs, followed by the sequencing of the partial DNA polymerase gene in order to identify the AdV species. The prevalence was 3.3 folds higher in NHPs than in humans. More than 1/3 (35.8%) of the NHPs and 1/10 (10.5%) of the humans excreted AdVs in their feces. The positive rate was high in great apes (46%), with a maximum of 54.2% in chimpanzees (Pan troglodytes) and 35.9% in gorillas (Gorilla gorilla), followed by monkeys (25.6%), with 27.5% in Barbary macaques (Macaca sylvanus) and 23.1% in baboons (seven Papio papio and six Papio hamadryas). No green monkeys (Chlorocebus sabaeus) were found to be positive for AdVs. The AdVs detected in NHPs were members of Human mastadenovirus E (HAdV-E), HAdV-C or HAdV-B, and those in the humans belonged to HAdV-C or HAdV-D. HAdV-C members were detected in both gorillas and humans, with evidence of zoonotic transmission since phylogenetic analysis revealed that gorilla AdVs belonging to HAdV-C were genetically identical to strains detected in humans who had been living around gorillas, and, inversely, a HAdV-C member HAdV type was detected in gorillas. This confirms the gorilla-to-human transmission of adenovirus. which has been reported previously. In addition, HAdV-E members, the most often detected here, are widely distributed among NHP species regardless of their origin, i.e., HAdV-E members seem to lack host specificity. Virus isolation was successful from a human sample and the strain of the Mbo024 genome, of 35 kb, that was identified as belonging to HAdV-D, exhibited close identity to HAdV-D members for all genes. This study provides information on the AdVs that infect African NHPs and the human populations living nearby, with an evident zoonotic transmission. It is likely that AdVs crossed the species barrier between different NHP species (especially HAdV-E members), between NHPs and humans (especially HAdV-C), but also between humans, NHPs and other animal species. url: https://www.ncbi.nlm.nih.gov/pubmed/32570742/ doi: 10.3390/v12060657 id: cord-277039-yo5ojr0s author: Mendenhall, Ian H. title: Discovery and Characterization of Novel Bat Coronavirus Lineages from Kazakhstan date: 2019-04-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronaviruses are positive-stranded RNA viruses that infect a variety of hosts, resulting in a range of symptoms from gastrointestinal illness to respiratory distress. Bats are reservoirs for a high diversity of coronaviruses, and focused surveillance detected several strains genetically similar to MERS-coronavirus, SARS-coronavirus, and the human coronaviruses 229E and NL63. The bat fauna of central Asia, which link China to eastern Europe, are relatively less studied than other regions of the world. Kazakhstan is the world’s ninth largest country; however, little is understood about the prevalence and diversity of bat-borne viruses. In this study, bat guano was collected from bat caves in three different sites of southern Kazakhstan that tested positive for coronaviruses. Our phylogenetic reconstruction indicates these are novel bat coronaviruses that belong to the genus Alphacoronavirus. In addition, two distinct lineages of Kazakhstan bat coronaviruses were detected. Both lineages are closely related to bat coronaviruses from China, France, Spain, and South Africa, suggesting that co-circulation of coronaviruses is common in multiple bat species with overlapping geographical distributions. Our study highlights the need for collaborative efforts in understudied countries to increase integrated surveillance capabilities toward better monitoring and detection of infectious diseases. url: https://doi.org/10.3390/v11040356 doi: 10.3390/v11040356 id: cord-273661-egpyvqrw author: Mo, Mei-Lan title: Molecular Characterization of Major Structural Protein Genes of Avian Coronavirus Infectious Bronchitis Virus Isolates in Southern China date: 2013-12-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: To gain comprehensive genetic information of circulating avian coronavirus infectious bronchitis virus (IBV) isolates in China, analysis of the phylogenetic tree, entropy of the amino acid sequences, and the positive selection as well as computational recombinations of S1, M and N genes of 23 IBV isolates was conducted in the present study. The phylogenetic trees based on the S1, M and N genes exhibited considerably different topology and the CK/CH/LSC/99I-type isolates were the predominant IBVs based on the phylogenetic analysis of S1 gene. Results of entropy of amino acid sequences revealed that the S1 gene had the largest variation; the M gene had less variation than the N gene. Positive selections were detected in not only S1 but also M and N gene proteins. In addition, five S1 gene recombinants between vaccine strain 4/91 and CK/CH/LSC/99I-type field isolate were confirmed. In conclusion, multiple IBV genotypes co-circulated; genetic diversity and positive selections existed in S1, M and N genes; 4/91 vaccine recombinants emerged in China. Our results show that field IBVs in China are continuing to evolve and vaccine strains may have an important role in the appearance of new IBV strains via recombination. In addition, the present study indicates that IBV evolution is driven by both generations of genetic diversity and selection. url: https://doi.org/10.3390/v5123007 doi: 10.3390/v5123007 id: cord-313312-h607itv2 author: Mok, Darren Z. L. title: The Effects of Pre-Existing Antibodies on Live-Attenuated Viral Vaccines date: 2020-05-08 words: 7417.0 sentences: 349.0 pages: flesch: 34.0 cache: ./cache/cord-313312-h607itv2.txt txt: ./txt/cord-313312-h607itv2.txt summary: Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. The clinical trial finding that subjects with a limited range of cross-reactive antibodies from a prior Japanese Encephalitis vaccine were able to enhance yellow fever vaccination, by prolonging vaccine viremia duration that leads to higher antibody titers, thus hints at the possibility that whether pre-existing antibodies inhibit or augment flavivirus infection will depend on both antibody titers and the type/specificity of antibodies produced [85] . By contrast, at sub-neutralizing titers, pre-existing antibodies can enable viruses to better infect cells and increase innate immune responses that augment LAV immunogenicity. By contrast, at sub-neutralizing titers, pre-existing antibodies can enable viruses to better infect cells and increase innate immune responses that augment LAV immunogenicity. abstract: Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy. However, with rapid increases in international travel, globalization, geographic spread of viral vectors, and widespread use of vaccines, there is an increasing need to consider how pre-exposure to viruses which share similar antigenic regions can impact vaccine efficacy. Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. On the other hand, pre-existing antibodies can augment flaviviral LAV efficacy such as that of dengue and yellow fever virus, especially when pre-existing antibodies are present at sub-neutralizing levels. The increased vaccine immunogenicity can be facilitated by antibody-dependent enhancement of virus infection, enhancing virus uptake in antigen-presenting cells, and robust induction of innate immune responses that promote vaccine immunogenicity. This review examines the literature on this topic and examines the circumstances where pre-existing antibodies can inhibit or enhance LAV efficacy. A better knowledge of the underlying mechanisms involved could allow us to better manage immunization in seropositive individuals and even identify possibilities that could allow us to exploit pre-existing antibodies to boost vaccine-induced responses for improved vaccine efficacy. url: https://www.ncbi.nlm.nih.gov/pubmed/32397218/ doi: 10.3390/v12050520 id: cord-260705-huyyw5z6 author: Moshe, Adi title: Virus-Induced Aggregates in Infected Cells date: 2012-10-17 words: 5063.0 sentences: 265.0 pages: flesch: 39.0 cache: ./cache/cord-260705-huyyw5z6.txt txt: ./txt/cord-260705-huyyw5z6.txt summary: During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intraand intercellular transportation. In plant cells, both RNA and DNA viruses are associated with large inclusions detected in the cytoplasm and nucleus, however, their role in virus propagation or oppositely in virus restraint is less investigated than in infected mammalian cells. In general, mammalian and plant viruses make use of aggregates as scaffolds for anchoring the replication complex, increasing the local concentration of viral and host components required for replication and assembly, and shielding the process of replication from host defense. abstract: During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. Identification of aggregates has become a useful diagnostic tool for certain viral infections. There is wide variety of viral aggregates, which differ by their location, size, content and putative function. The role of aggregation in the context of a specific virus is often poorly understood, especially in the case of plant viruses. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intra- and intercellular transportation. Aggregated structures may protect viral functional complexes from the cellular degradation machinery. Alternatively, the activation of host defense mechanisms may involve sequestration of virus components in aggregates, followed by their neutralization as toxic for the host cell. The diversity of virus-induced aggregates in mammalian and plant cells is the subject of this review. url: https://www.ncbi.nlm.nih.gov/pubmed/23202461/ doi: 10.3390/v4102218 id: cord-003284-hjx2d5rq author: Márquez-Jurado, Silvia title: An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo date: 2018-10-07 words: 9917.0 sentences: 409.0 pages: flesch: 51.0 cache: ./cache/cord-003284-hjx2d5rq.txt txt: ./txt/cord-003284-hjx2d5rq.txt summary: Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. To analyze the genetic stability of the recombinant ZIKV harboring the point mutation A175V in the coding region of the NS2A protein (rZIKV-RGN-mNS2A), total RNA was purified from Vero cells infected with viruses from passage 1 (P1) to passage 5 (P5) using the RNeasy minikit (Qiagen), according to the manufacturer''s specifications. To investigate whether the reduced RNA synthesis of rZIKV-RGN-mNS2A in Vero cells could result in viral attenuation in vivo, the ability of the mutant virus to induce pathogenesis was analyzed in A129 mice and compared with that of the parental rZIKV-RGN ( Figure 6 ). abstract: The recent outbreaks of Zika virus (ZIKV), its association with Guillain–Barré syndrome and fetal abnormalities, and the lack of approved vaccines and antivirals, highlight the importance of developing countermeasures to combat ZIKV disease. In this respect, infectious clones constitute excellent tools to accomplish these goals. However, flavivirus infectious clones are often difficult to work with due to the toxicity of some flavivirus sequences in bacteria. To bypass this problem, several alternative approaches have been applied for the generation of ZIKV clones including, among others, in vitro ligation, insertions of introns and using infectious subgenomic amplicons. Here, we report a simple and novel DNA-launched approach based on the use of a bacterial artificial chromosome (BAC) to generate a cDNA clone of Rio Grande do Norte Natal ZIKV strain. The sequence was identified from the brain tissue of an aborted fetus with microcephaly. The BAC clone was fully stable in bacteria and the infectious virus was efficiently recovered in Vero cells through direct delivery of the cDNA clone. The rescued virus yielded high titers in Vero cells and was pathogenic in a validated mouse model (A129 mice) of ZIKV infection. Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. This BAC approach provides a stable and reliable reverse genetic system for ZIKV that will help to identify viral determinants of virulence and facilitate the development of vaccine and therapeutic strategies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212934/ doi: 10.3390/v10100547 id: cord-002185-oz7hras7 author: Nelson, Elizabeth A. title: Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications date: 2016-08-02 words: 5047.0 sentences: 249.0 pages: flesch: 52.0 cache: ./cache/cord-002185-oz7hras7.txt txt: ./txt/cord-002185-oz7hras7.txt summary: In this system, 4-hydroxy-zuclomiphene appeared more potent than the Our previous findings indicated that clomiphene blocks EBOV infection by blocking entry of viral particles into the cell cytoplasm [20, 29] ; this effect appears to be at the level of fusion between the membrane of the viral particle and the limiting membrane of an Niemann-Pick disease, type C1 positive (NPC1 + ) endolysosome, the site of EBOV fusion [30] [31] [32] . Similar results were seen when comparing eight doses of clomiphene and zuclomiphene in trVLP infection ( Figure 5A ) and VLP entry ( Figure 5B ) assays. Where tested, they were equally effective to each other in two cell types and for entry mediated by three filoviral GPs. 4-hydroxy-enclomiphene, and 4-hydroxy-zuclomiphene also blocked EBOV trVLP infection and VLP entry under the abstract: The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997570/ doi: 10.3390/v8080206 id: cord-287647-0nyquokt author: Nemoto, Manabu title: The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland date: 2019-10-14 words: 2715.0 sentences: 139.0 pages: flesch: 57.0 cache: ./cache/cord-287647-0nyquokt.txt txt: ./txt/cord-287647-0nyquokt.txt summary: The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. In contrast in Japan, although an outbreak of diarrhoea occurred among ECoV-infected draft horses at one racecourse [4] [5] [6] , there have been no similar outbreaks subsequently, and all rectal swabs collected from diarrheic Thoroughbred foals were negative. Furthermore, only 2.5% of the rectal swabs collected from healthy foals in the largest Thoroughbred horse breeding region in Japan were positive for ECoV [13] . This study provides the first report of ECoV circulating in Ireland, the third European country with a significant horse industry where the virus has been detected in horses with enteric disease. This is the first report of ECoV detection in faeces samples from both foals and adult horses in Ireland. Low prevalence of equine coronavirus in foals in the largest Thoroughbred horse breeding region of Japan abstract: The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. A total of 424 clinical samples were examined from equids with enteric disease in 24 Irish counties between 2011 and 2015. A real-time reverse transcription polymerase chain reaction was used to detect ECoV RNA. Nucleocapsid, spike and the region from the p4.7 to p12.7 genes of positive samples were sequenced, and sequence and phylogenetic analyses were conducted. Five samples (1.2%) collected in 2011 and 2013 tested positive for ECoV. Positive samples were collected from adult horses, Thoroughbred foals and a donkey foal. Sequence and/or phylogenetic analysis showed that nucleocapsid, spike and p12.7 genes were highly conserved and were closely related to ECoVs identified in other countries. In contrast, the region from p4.7 and the non-coding region following the p4.7 gene had deletions or insertions. The differences in the p4.7 region between the Irish ECoVs and other ECoVs indicated that the Irish viruses were distinguishable from those circulating in other countries. This is the first report of ECoV detected in both foals and adult horses in Ireland. url: https://www.ncbi.nlm.nih.gov/pubmed/31615132/ doi: 10.3390/v11100946 id: cord-321673-v5o49ees author: Nieto-Torres, Jose L. title: Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis date: 2015-07-03 words: 8398.0 sentences: 451.0 pages: flesch: 38.0 cache: ./cache/cord-321673-v5o49ees.txt txt: ./txt/cord-321673-v5o49ees.txt summary: Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Noticeably, these proteins oligomerize in cell membranes to form ion conductive pores, which generally display mild ion selectivity, indicating that viroporins do not show preference for particular ionic species. Influenza viruses lacking M2 ion conductivity, presented either a 15-fold reduction of viral titer in tissue culture [74] , or showed a standard production in cell culture but a restricted growth in the nasal turbinates of infected mice [75] . Several compounds inhibit viroporin ion conductivity in artificial lipid membranes, and some of them efficiently reduce viral growth when administered to infected cells. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV-1-infected cells abstract: Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology. url: https://www.ncbi.nlm.nih.gov/pubmed/26151305/ doi: 10.3390/v7072786 id: cord-011635-vosu7y6j author: Norlander, Allison E. title: Innate Type 2 Responses to Respiratory Syncytial Virus Infection date: 2020-05-08 words: 8260.0 sentences: 458.0 pages: flesch: 46.0 cache: ./cache/cord-011635-vosu7y6j.txt txt: ./txt/cord-011635-vosu7y6j.txt summary: This review summarizes the contribution of a newly described cell type, group 2 innate lymphoid cells (ILC2), and epithelial-derived alarmin proteins that activate ILC2, including IL-33, IL-25, thymic stromal lymphopoietin (TSLP), and high mobility group box 1 (HMGB1). Furthermore, the epithelial-derived cytokines interleukin-33 (IL-33), interleukin-25 (IL-25), and thymic stromal lymphopoietin (TSLP), as well as the innate immune cell-derived cytokine high mobility group box 1 (HMGB1), activate and induce ILC2 function, thereby promoting the progression of type 2-mediated pulmonary diseases ( Figure 1 ) [59] [60] [61] [62] [63] [64] . These alarmin proteins released from RSV-infected epithelial cells can activate group 2 innate lymphoid cells (ILC2) to produce the type 2 cytokines IL-5 and IL-13. These alarmin proteins released from RSV-infected epithelial cells can activate group 2 innate lymphoid cells (ILC2) to produce the type 2 cytokines IL-5 and IL-13. Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection abstract: Respiratory syncytial virus (RSV) is a common and contagious virus that results in acute respiratory tract infections in infants. In many cases, the symptoms of RSV remain mild, however, a subset of individuals develop severe RSV-associated bronchiolitis. As such, RSV is the chief cause of infant hospitalization within the United States. Typically, the immune response to RSV is a type 1 response that involves both the innate and adaptive immune systems. However, type 2 cytokines may also be produced as a result of infection of RSV and there is increasing evidence that children who develop severe RSV-associated bronchiolitis are at a greater risk of developing asthma later in life. This review summarizes the contribution of a newly described cell type, group 2 innate lymphoid cells (ILC2), and epithelial-derived alarmin proteins that activate ILC2, including IL-33, IL-25, thymic stromal lymphopoietin (TSLP), and high mobility group box 1 (HMGB1). ILC2 activation leads to the production of type 2 cytokines and the induction of a type 2 response during RSV infection. Intervening in this innate type 2 inflammatory pathway may have therapeutic implications for severe RSV-induced disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290766/ doi: 10.3390/v12050521 id: cord-317715-xtsi663k author: Ortiz-Riaño, Emilio title: D471G Mutation in LCMV-NP Affects its Ability to Self-associate and Results in a Dominant Negative Effect in Viral RNA Synthesis date: 2012-10-16 words: 9164.0 sentences: 483.0 pages: flesch: 52.0 cache: ./cache/cord-317715-xtsi663k.txt txt: ./txt/cord-317715-xtsi663k.txt summary: Reporter gene activation (FFL) is shown as percentage (%) of LCMV NP-NP wt interaction (pC-NP-VP16 and pC-NP-GAL4) after normalization of transfection efficiencies with the Renilla luciferase expression plasmid pRL SV40 (ii). Unexpectedly, the D471A substitution impeded both NP-NP and NP-Z interactions, as well as NP functions in replication and transcription of the LCMV MG and the ability of NP to counteract SeV-mediated induction of the host IFN-I response, suggesting that change D to A at position 471 might have affected the overall structure of NP without affecting its stability as reflected by its unchanged expression levels determined by WB using anti-VP16 ( Figures 6A and 6B ) or anti-HA ( Figures 6C and 6D) antibodies. (C) Replication and transcription activity: BHK-21 cells were co-transfected with the LCMV MG as described in Figure 3 together with expression plasmids for the viral polymerase (L) and wt or indicated mutant NPs, and pSV40-Cluc expression vector to normalize transfection efficiencies. abstract: Arenaviruses merit significant interest because several family members are etiological agents of severe hemorrhagic fevers, representing a major burden to public health. Currently, there are no FDA-licensed vaccines against arenaviruses and the only available antiviral therapy is limited to the use of ribavirin that is partially effective. Arenavirus nucleoprotein (NP) is found associated with the genomic RNA forming the viral ribonucleoproteins (vRNPs) that together with the polymerase (L) direct viral replication and transcription. Virion formation requires the recruitment of vRNPs into budding sites, a process in which the arenavirus matrix-like protein (Z) plays a major role. Therefore, proper NP-NP and NP-Z interactions are required for the generation of infectious progeny. In this work we demonstrate the role of the amino acid residue D471 in the self-association of lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP). Amino acid substitutions at this position abrogate NP oligomerization, affecting its ability to mediate replication and transcription of a minigenome reporter plasmid. However, its ability to interact with the Z protein, counteract the cellular interferon response and bind to dsRNA analogs was retained. Additionally, we also document the dominant negative effect of D471G mutation on viral infection, suggesting that NP self-association is an excellent target for the development of new antivirals against arenaviruses. url: https://doi.org/10.3390/v4102137 doi: 10.3390/v4102137 id: cord-337339-0vkigjv2 author: Osterrieder, Nikolaus title: Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters date: 2020-07-20 words: 4327.0 sentences: 220.0 pages: flesch: 47.0 cache: ./cache/cord-337339-0vkigjv2.txt txt: ./txt/cord-337339-0vkigjv2.txt summary: We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information, as this small-animal model appears to mirror age-dependent differences in human patients. Moreover, transgenic mice expressing human ACE2 represent a lethal SARS-CoV-2 infection model resulting in significant weight loss and permitting robust virus replication in the respiratory tract including the lungs [20] . In contrast to SARS-CoV-2 titers, histopathological changes differed markedly between young and aged Syrian hamsters over time: younger animals launched more severe reactions at early time points after infection, while lesions and inflammation in the lungs became more pronounced and widespread at later time points in the elderly. Based on the data presented here, we propose that comparative preclinical assessments of SARS-CoV-2 vaccines and other treatment options in young versus aged hamsters may yield valuable and relevant results, as this small animal model appears to mimic age-dependent differences in humans. abstract: In late 2019, an outbreak of a severe respiratory disease caused by an emerging coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans. Complete understanding of COVID-19, the multi-faceted disease caused by SARS-CoV-2, requires suitable small animal models, as does the development and evaluation of vaccines and antivirals. Since age-dependent differences of COVID-19 were identified in humans, we compared the course of SARS-CoV-2 infection in young and aged Syrian hamsters. We show that virus replication in the upper and lower respiratory tract was independent of the age of the animals. However, older hamsters exhibited more pronounced and consistent weight loss. In situ hybridization in the lungs identified viral RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. Histopathology revealed clear age-dependent differences, with young hamsters launching earlier and stronger immune cell influx than aged hamsters. The latter developed conspicuous alveolar and perivascular edema, indicating vascular leakage. In contrast, we observed rapid lung recovery at day 14 after infection only in young hamsters. We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information, as this small-animal model appears to mirror age-dependent differences in human patients. url: https://www.ncbi.nlm.nih.gov/pubmed/32698441/ doi: 10.3390/v12070779 id: cord-012845-so2umdlt author: Paczesny, Jan title: Recent Progress in the Detection of Bacteria Using Bacteriophages: A Review date: 2020-08-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Bacteria will likely become our most significant enemies of the 21st century, as we are approaching a post-antibiotic era. Bacteriophages, viruses that infect bacteria, allow us to fight infections caused by drug-resistant bacteria and create specific, cheap, and stable sensors for bacteria detection. Here, we summarize the recent developments in the field of phage-based methods for bacteria detection. We focus on works published after mid-2017. We underline the need for further advancements, especially related to lowering the detection (below 1 CFU/mL; CFU stands for colony forming units) and shortening the time of analysis (below one hour). From the application point of view, portable, cheap, and fast devices are needed, even at the expense of sensitivity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472331/ doi: 10.3390/v12080845 id: cord-335279-cfv18qn0 author: Paillot, Romain title: Special Issue “Equine Viruses”: Old “Friends” and New Foes? date: 2020-01-29 words: 2070.0 sentences: 112.0 pages: flesch: 49.0 cache: ./cache/cord-335279-cfv18qn0.txt txt: ./txt/cord-335279-cfv18qn0.txt summary: With this Special Issue, which assembles a collection of communications, research articles, and reviews, we intend to explore our understanding of a panel of equine viruses, looking at their pathogenicity, their importance in terms of welfare and potential association with diseases, their economic importance and impact on performance, and how their identification can be helped by new technologies and methods. The authors highlight the potential protective role of eqMx1, which primarily targets the virus nucleoprotein (NP), against the transmission of new IAVs in horses (i.e., eqMx1 could only inhibit the polymerase activity of IAVs of avian and human origin but remained inactive against the equine IAVs tested). To date, equine influenza virus remains one of the most important respiratory pathogens of horses worldwide, with a potential damaging impact on the equine industry, as clearly illustrated in 2007 in Australia and in 2019 in Europe [20, 21] . abstract: The Food and Agriculture Organization of the United Nations has recently estimated that the world equid population exceeds 110 million (FAOSTAT 2017).[...]. url: https://www.ncbi.nlm.nih.gov/pubmed/32013127/ doi: 10.3390/v12020153 id: cord-269249-7ubs3q6p author: Paim, Francine C. title: Epidemiology of Deltacoronaviruses (δ-CoV) and Gammacoronaviruses (γ-CoV) in Wild Birds in the United States date: 2019-09-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Porcine deltacoronavirus (δ-CoV) is the object of extensive research in several countries including the United States. In contrast, the epidemiology of δ-CoVs in wild birds in the US is largely unknown. Our aim was to comparatively assess the prevalence of δ- and γ-CoVs in wild migratory terrestrial and aquatic birds in Arkansas, Illinois, Indiana, Maryland, Mississippi, Missouri, Ohio, Tennessee and Wisconsin. A total of 1236 cloacal/fecal swabs collected during the period 2015–2018 were tested for γ- and δ-CoVs using genus-specific reverse transcription-PCR assays. A total of 61 (4.99%) samples were γ-CoV positive, with up to 29 positive samples per state. In contrast, only 14 samples were positive for δ-CoV (1.14%) with only 1–4 originating from the same state. Thus, unlike previous reports from Asia, γ-CoVs are more prevalent than δ-CoVs in the US, suggesting that δ-CoVs may spread in birds with lower efficiency. This may indicate δ-CoV emerging status and incomplete adaptation to new host species limiting its spread. Phylogenetic analysis of the partial N gene revealed that the newly identified δ-CoV strains were most closely related to the HKU20 (wigeon) strain. Further studies are necessary to investigate the role of aquatic bird δ-CoVs in the epidemiology of δ-CoVs in swine and terrestrial birds. url: https://www.ncbi.nlm.nih.gov/pubmed/31561462/ doi: 10.3390/v11100897 id: cord-317496-6o2upns3 author: Pascual-Iglesias, Alejandro title: Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV)—Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV date: 2019-07-25 words: 7100.0 sentences: 404.0 pages: flesch: 48.0 cache: ./cache/cord-317496-6o2upns3.txt txt: ./txt/cord-317496-6o2upns3.txt summary: In this line, we engineered an attenuated virus based on the transmissible gastroenteritis virus (TGEV) genome, expressing a chimeric spike protein from a virulent United States (US) PEDV strain. The rTGEV-RS-SPEDV vaccine candidate was also attenuated in three-week-old animals that were used to evaluate the protection conferred by this virus, compared with the protection induced by infection with a virulent PEDV US strain (PEDV-NVSL). Interestingly, Viruses 2019, 11, 682 9 of 18 when viral RNA was isolated from feces of 21-day-old piglets at seven days post-vaccination (see below) and rTGEV-RS-SPEDV virus was sequenced, the same modifications were observed. An attenuated chimeric rTGEV virus expressing the ectodomain of a virulent US PEDV S protein (rTGEV-RS-SPEDV) was engineered as vaccine candidate for PEDV and evaluated in a young piglet model system. An attenuated chimeric rTGEV virus expressing the ectodomain of a virulent US PEDV S protein (rTGEV-RS-SPEDV) was engineered as vaccine candidate for PEDV and evaluated in a young piglet model system. abstract: Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide. Although both inactivated and live attenuated vaccines have been extensively used, the emergence of highly virulent strains and the recurrent outbreaks even in vaccinated farms highlight the need of effective vaccines. Engineering of genetically defined live attenuated vaccines is a rational approach for novel vaccine development. In this line, we engineered an attenuated virus based on the transmissible gastroenteritis virus (TGEV) genome, expressing a chimeric spike protein from a virulent United States (US) PEDV strain. This virus (rTGEV-RS-SPEDV) was attenuated in highly-sensitive five-day-old piglets, as infected animals did not lose weight and none of them died. In addition, the virus caused very minor tissue damage compared with a virulent virus. The rTGEV-RS-SPEDV vaccine candidate was also attenuated in three-week-old animals that were used to evaluate the protection conferred by this virus, compared with the protection induced by infection with a virulent PEDV US strain (PEDV-NVSL). The rTGEV-RS-SPEDV virus protected against challenge with a virulent PEDV strain, reducing challenge virus titers in jejunum and leading to undetectable challenge virus RNA levels in feces. The rTGEV-RS-SPEDV virus induced a humoral immune response specific for PEDV, including neutralizing antibodies. Altogether, the data indicated that rTGEV-RS-SPEDV is a promising vaccine candidate against virulent PEDV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/31349683/ doi: 10.3390/v11080682 id: cord-003859-k8wfyj9b author: Paweska, Janusz T. title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera date: 2019-07-24 words: 6407.0 sentences: 308.0 pages: flesch: 51.0 cache: ./cache/cord-003859-k8wfyj9b.txt txt: ./txt/cord-003859-k8wfyj9b.txt summary: title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). The purpose of this study was to evaluate and compare the diagnostic performance of EBOV IgG-indirect ELISAs based on antigens produced by classical virological and recombinant protein expression methods using human serum panels from EBOV non-infected and EBOV infected humans. abstract: Filovirus serological diagnosis and epidemiological investigations are hampered due to the unavailability of validated immunoassays. Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. One I-ELISA was based on a whole EBOV antigen (WAg) and two utilized recombinant nucleocapsid (NP) and glycoproteins (GP), respectively. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). At the cut-off values selected at 95% accuracy level by the two-graph receiver operating characteristic analysis, specificity in the SA EBOV negative serum panel (n = 273) ranged from 98.17% (GP ELISA) to 99.27% (WAg ELISA). Diagnostic specificity in the SL EBOV negative panel (n = 676) was 100% by the three ELISAs. The diagnostic sensitivity in 423 RT-PCR confirmed EBOD patients was dependent on the time when the serum was collected after onset of disease. It significantly increased 2 weeks post-onset, reaching 100% sensitivity by WAg and NP and 98.1% by GP I-ELISA. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722596/ doi: 10.3390/v11080678 id: cord-352619-s2x53grh author: Payne, Natalie title: Novel Circoviruses Detected in Feces of Sonoran Felids date: 2020-09-15 words: 3263.0 sentences: 177.0 pages: flesch: 45.0 cache: ./cache/cord-352619-s2x53grh.txt txt: ./txt/cord-352619-s2x53grh.txt summary: Genomes from several families of circular Rep-encoding single-stranded DNA viruses (CRESS-DNA viruses) are part of the phylum Cressdnaviricota [22] and have been identified in fecal samples of other mammals, including domestic cats [23, 24] , bobcats, African lions [25] , capybaras [26] , and Tasmanian devils [27] . Here we used a metagenomic approach to identify novel circoviruses in the feces of two species of Sonoran felids, the puma and bobcat; although not endangered, knowledge of viral threats facing these species could help prevent future population decline, as well as indicate potential threats to the endangered ocelot and jaguar. Based on the species-demarcation threshold for circoviruses which is 80% genome-wide identity [28] , both of these belong to a new species which we refer to as Sonfela (derived from Sonoran felid associated) circovirus 1. As the viral genomes were derived from scat samples, the circoviruses could have infected the bobcat prey species or the felids themselves or be environmentally derived. abstract: Sonoran felids are threatened by drought and habitat fragmentation. Vector range expansion and anthropogenic factors such as habitat encroachment and climate change are altering viral evolutionary dynamics and exposure. However, little is known about the diversity of viruses present in these populations. Small felid populations with lower genetic diversity are likely to be most threatened with extinction by emerging diseases, as with other selective pressures, due to having less adaptive potential. We used a metagenomic approach to identify novel circoviruses, which may have a negative impact on the population viability, from confirmed bobcat (Lynx rufus) and puma (Puma concolor) scats collected in Sonora, Mexico. Given some circoviruses are known to cause disease in their hosts, such as porcine and avian circoviruses, we took a non-invasive approach using scat to identify circoviruses in free-roaming bobcats and puma. Three circovirus genomes were determined, and, based on the current species demarcation, they represent two novel species. Phylogenetic analyses reveal that one circovirus species is more closely related to rodent associated circoviruses and the other to bat associated circoviruses, sharing highest genome-wide pairwise identity of approximately 70% and 63%, respectively. At this time, it is unknown whether these scat-derived circoviruses infect felids, their prey, or another organism that might have had contact with the scat in the environment. Further studies should be conducted to elucidate the host of these viruses and assess health impacts in felids. url: https://doi.org/10.3390/v12091027 doi: 10.3390/v12091027 id: cord-351955-9l4786lb author: Pedersen, Niels C. title: Significance of Coronavirus Mutants in Feces and Diseased Tissues of Cats Suffering from Feline Infectious Peritonitis date: 2009-08-26 words: 6785.0 sentences: 322.0 pages: flesch: 58.0 cache: ./cache/cord-351955-9l4786lb.txt txt: ./txt/cord-351955-9l4786lb.txt summary: Complete structural (S, E, M, N) and accessory (3a-c and 7 a, b) gene sequences were obtained from diseased omentum of the four related cats that died of FIP and the isolates designated were FIPV-UCD11, 12, 13 and 14 ( Table 1 ). The coronavirus isolated from Lucy''s feces (designated FECV-UCD3) had an intact (i.e., wild type or non-deliterious) 3c and its sequence was otherwise 99% identical to the sequence of FIPV-UCD14 found in her diseased omentum. FECV-UCD4, was most closely related to the FIPV isolated from Lucy and was 99.7% related to the consensus nucleotide sequences of coronaviruses obtained from the four related FIP cats ( Figure 1 , Table 2 ). The 3c gene sequence of the fecal virus of cat 388406 was intact and ≥99% related to the FIPV found in diseased tissue ( Table 2 ). abstract: The internal FECV→FIPV mutation theory and three of its correlates were tested in four sibs/half-sib kittens, a healthy contact cat, and in four unrelated cats that died of FIP at geographically disparate regions. Coronavirus from feces and extraintestinal FIP lesions from the same cat were always >99% related in accessory and structural gene sequences. SNPs and deletions causing a truncation of the 3c gene product were found in almost all isolates from the diseased tissues of the eight cats suffering from FIP, whereas most, but not all fecal isolates from these same cats had intact 3c genes. Other accessory and structural genes appeared normal in both fecal and lesional viruses. Deliterious mutations in the 3c gene were unique to each cat, indicating that they did not originate in one cat and were subsequently passed horizontally to the others. Compartmentalization of the parental and mutant forms was not absolute; virus of lesional type was sometimes found in feces of affected cats and virus identical to fecal type was occasionally identified in diseased tissues. Although 3c gene mutants in this study were not horizontally transmitted, the parental fecal virus was readily transmitted by contact from a cat that died of FIP to its housemate. There was a high rate of mutability in all structural and accessory genes both within and between cats, leading to minor genetic variants. More than one variant could be identified in both diseased tissues and feces of the same cat. Laboratory cats inoculated with a mixture of two closely related variants from the same FIP cat developed disease from one or the other variant, but not both. Significant genetic drift existed between isolates from geographically distinct regions of the Western US. url: https://doi.org/10.3390/v1020166 doi: 10.3390/v1020166 id: cord-004335-bw3tziup author: Perez-Zsolt, Daniel title: When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses date: 2019-12-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dendritic cells (DCs) are among the first cells that recognize incoming viruses at the mucosal portals of entry. Initial interaction between DCs and viruses facilitates cell activation and migration to secondary lymphoid tissues, where these antigen presenting cells (APCs) prime specific adaptive immune responses. Some viruses, however, have evolved strategies to subvert the migratory capacity of DCs as a way to disseminate infection systemically. Here we focus on the role of Siglec-1, a sialic acid-binding type I lectin receptor potently upregulated by type I interferons on DCs, that acts as a double edge sword, containing viral replication through the induction of antiviral immunity, but also favoring viral spread within tissues. Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019426/ doi: 10.3390/v12010008 id: cord-347053-m5m4zgfy author: Pharo, Elizabeth A. title: Host–Pathogen Responses to Pandemic Influenza H1N1pdm09 in a Human Respiratory Airway Model date: 2020-06-24 words: 9450.0 sentences: 554.0 pages: flesch: 50.0 cache: ./cache/cord-347053-m5m4zgfy.txt txt: ./txt/cord-347053-m5m4zgfy.txt summary: wdNHBE cells produced an innate immune response to IAV-infection with increased transcription of proand anti-inflammatory cytokines and chemokines and the antiviral viperin but reduced expression of the mucin-encoding MUC5B, which may impair mucociliary clearance. The cytopathic effect of H1N1pdm09 included damage to the airway epithelium, the induction of innate immune responses including the expression of pro-and anti-inflammatory cytokines and chemokines and antiviral genes and proteins, consistent with pulmonary host defense. Key genes upregulated in our H1N1pdm09 in vitro challenge model, mimic the innate immune and inflammatory response in human patients in vivo infected with the 2009 pandemic IAV. The more than 350-fold induction of the antiviral-encoding RSAD2 (viperin) gene in our pandemic IAV-infected wdNHBE cells confirms the antiviral response of the airway epithelium in vitro. The disruption of the airway epithelium by IAV H1N1pdm09 and poly(I:C), plus the induction of the innate immune response and antiviral, and pro-and anti-inflammatory genes demonstrated the viability of this model to investigate pandemic influenza. abstract: The respiratory Influenza A Viruses (IAVs) and emerging zoonotic viruses such as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pose a significant threat to human health. To accelerate our understanding of the host–pathogen response to respiratory viruses, the use of more complex in vitro systems such as normal human bronchial epithelial (NHBE) cell culture models has gained prominence as an alternative to animal models. NHBE cells were differentiated under air-liquid interface (ALI) conditions to form an in vitro pseudostratified epithelium. The responses of well-differentiated (wd) NHBE cells were examined following infection with the 2009 pandemic Influenza A/H1N1pdm09 strain or following challenge with the dsRNA mimic, poly(I:C). At 30 h postinfection with H1N1pdm09, the integrity of the airway epithelium was severely impaired and apical junction complex damage was exhibited by the disassembly of zona occludens-1 (ZO-1) from the cell cytoskeleton. wdNHBE cells produced an innate immune response to IAV-infection with increased transcription of pro- and anti-inflammatory cytokines and chemokines and the antiviral viperin but reduced expression of the mucin-encoding MUC5B, which may impair mucociliary clearance. Poly(I:C) produced similar responses to IAV, with the exception of MUC5B expression which was more than 3-fold higher than for control cells. This study demonstrates that wdNHBE cells are an appropriate ex-vivo model system to investigate the pathogenesis of respiratory viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32599823/ doi: 10.3390/v12060679 id: cord-003915-kje8lvgl author: Pigeyre, Laetitia title: Interaction of a Densovirus with Glycans of the Peritrophic Matrix Mediates Oral Infection of the Lepidopteran Pest Spodoptera frugiperda date: 2019-09-17 words: 9040.0 sentences: 462.0 pages: flesch: 47.0 cache: ./cache/cord-003915-kje8lvgl.txt txt: ./txt/cord-003915-kje8lvgl.txt summary: As orally transmitted viruses, densoviruses, are also challenged by the complexity of the insect gut barriers, more specifically by the chitinous peritrophic matrix, that lines and protects the midgut epithelium; how capsids stick to and cross these barriers to reach their final cell destination where replication goes has been poorly studied in insects. In addition, we showed that JcDV early infection results in (i) an arrest of N-Acetylglucosamine (GlcNAc) secretion by epithelial cells associated with a disorganization of the PM structure mimicking the effect of chitin-binding plant lectin; (ii) substantial changes in the expression of gut genes, which may also contribute to an early gut dysfunction and participate to viral pathogenesis. Results presented here show that JcDV capsids display carbohydrate-binding properties that insure recognition of the peritrophic matrix and determines caterpillars oral infection. abstract: The success of oral infection by viruses depends on their capacity to overcome the gut epithelial barrier of their host to crossing over apical, mucous extracellular matrices. As orally transmitted viruses, densoviruses, are also challenged by the complexity of the insect gut barriers, more specifically by the chitinous peritrophic matrix, that lines and protects the midgut epithelium; how capsids stick to and cross these barriers to reach their final cell destination where replication goes has been poorly studied in insects. Here, we analyzed the early interaction of the Junonia coenia densovirus (JcDV) with the midgut barriers of caterpillars from the pest Spodoptera frugiperda. Using combination of imaging, biochemical, proteomic and transcriptomic analyses, we examined in vitro, ex vivo and in vivo the early interaction of the capsids with the peritrophic matrix and the consequence of early oral infection on the overall gut function. We show that the JcDV particle rapidly adheres to the peritrophic matrix through interaction with different glycans including chitin and glycoproteins, and that these interactions are necessary for oral infection. Proteomic analyses of JcDV binding proteins of the peritrophic matrix revealed mucins and non-mucins proteins including enzymes already known to act as receptors for several insect pathogens. In addition, we show that JcDV early infection results in an arrest of N-Acetylglucosamine secretion and a disruption in the integrity of the peritrophic matrix, which may help viral particles to pass through. Finally, JcDV early infection induces changes in midgut genes expression favoring an increased metabolism including an increased translational activity. These dysregulations probably participate to the overall dysfunction of the gut barrier in the early steps of viral pathogenesis. A better understanding of early steps of densovirus infection process is crucial to build biocontrol strategies against major insect pests. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783882/ doi: 10.3390/v11090870 id: cord-353365-ujz5nkk3 author: Pirnay, Jean-Paul title: Study of a SARS-CoV-2 Outbreak in a Belgian Military Education and Training Center in Maradi, Niger date: 2020-08-27 words: 4773.0 sentences: 246.0 pages: flesch: 53.0 cache: ./cache/cord-353365-ujz5nkk3.txt txt: ./txt/cord-353365-ujz5nkk3.txt summary: The medical military command implemented testing of all Belgian soldiers for SARS-CoV-2 viral load and antibodies, two to three days before their departure on a mission abroad or on the high seas, and for specific missions immediately upon their return in Belgium. The SARS-CoV-2 outbreak in a Belgian military education and training center in Maradi, Niger, was characterized by mild symptoms in five soldiers and asymptomatic infection in two soldiers (one trainer), both having a viral load, as diagnosed upon their timely return to Belgium. The SARS-CoV-2 outbreak in a Belgian military education and training center in Maradi, Niger, was characterized by mild symptoms in five soldiers and asymptomatic infection in two soldiers (one trainer), both having a viral load, as diagnosed upon their timely return to Belgium. abstract: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compromises the ability of military forces to fulfill missions. At the beginning of May 2020, 22 out of 70 Belgian soldiers deployed to a military education and training center in Maradi, Niger, developed mild COVID-19 compatible symptoms. Immediately upon their return to Belgium, and two weeks later, all seventy soldiers were tested for SARS-CoV-2 RNA (RT-qPCR) and antibodies (two immunoassays). Nine soldiers had at least one positive COVID-19 diagnostic test result. Five of them exhibited COVID-19 symptoms (mainly anosmia, ageusia, and fever), while four were asymptomatic. In four soldiers, SARS-CoV-2 viral load was detected and the genomes were sequenced. Conventional and genomic epidemiological data suggest that these genomes have an African most recent common ancestor and that the Belgian military service men were infected through contact with locals. The medical military command implemented testing of all Belgian soldiers for SARS-CoV-2 viral load and antibodies, two to three days before their departure on a mission abroad or on the high seas, and for specific missions immediately upon their return in Belgium. Some military operational settings (e.g., training camps in austere environments and ships) were also equipped with mobile infectious disease (COVID-19) testing capacity. url: https://www.ncbi.nlm.nih.gov/pubmed/32867108/ doi: 10.3390/v12090949 id: cord-253282-zwl0safn author: Plant, Ewan P. title: Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production date: 2013-01-18 words: 5007.0 sentences: 266.0 pages: flesch: 55.0 cache: ./cache/cord-253282-zwl0safn.txt txt: ./txt/cord-253282-zwl0safn.txt summary: In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. Here, analyses using synonymous protein coding mutations demonstrate that the region of the genome that harbors the frameshift signal affects the regulation of genomic and subgenomic RNA production without altering protein sequence. Here we describe deletion and mutagenesis experiments with a dual luciferase reporter to show that the effect the sequence between stems 1 and 2 has on frameshifting efficiency is due to structural changes those mutations cause in the pseudoknot. Similar to previously described viruses containing mutations in the slippery site of the frameshift signal [7] , here we show that mutations to the SARS-CoV frameshift stimulating mRNA pseudoknot can also affect the production of viral genomic RNA. abstract: In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. It was not clear if these differences were due to changes in genomic sequence, the protein sequence or the frequency of frameshifting. Here, viruses with synonymous codon changes are shown to produce different ratios of genomic and subgenomic RNA. These findings demonstrate that the protein sequence is not the primary cause of altered genomic and subgenomic RNA production. The synonymous codon changes affect both the structure of the frameshift signal and frameshifting efficiency. Small differences in frameshifting efficiency result in dramatic differences in genomic RNA production and TCID(50) suggesting that the frameshifting frequency must stay above a certain threshold for optimal virus production. The data suggest that either the RNA sequence or the ratio of viral proteins resulting from different levels of frameshifting affects viral replication. url: https://doi.org/10.3390/v5010279 doi: 10.3390/v5010279 id: cord-302716-wfla3l20 author: Popov, Vsevolod L. title: Electron Microscopy in Discovery of Novel and Emerging Viruses from the Collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) date: 2019-05-25 words: 5445.0 sentences: 318.0 pages: flesch: 45.0 cache: ./cache/cord-302716-wfla3l20.txt txt: ./txt/cord-302716-wfla3l20.txt summary: Viruses can be differentiated by their specific morphology (ultrastructure): shape, size, intracellular location, or from the ultrastructural cytopathic effects and specific structures forming in the host cell Upolu, Aransas Bay [22] , Sinu [23] , and Trinity [24] orthobunyaviruses [25] [26] [27] , nyamiviruses [28] , a new reovirus from Cameroon (Fako virus) [29] and Colombia [30] , a new paramyxovirus [31] , an insect-specific (capable of replication in insects but not in vertebrates) alphavirus [32] , a new flavivirus genus [33] and other novel flaviviruses [34] [35] [36] [37] and rhabdoviruses [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] . Insect-specific viruses isolated recently from mosquitoes and phlebotomine sandflies have been characterized and proposed to represent a new genus (Negevirus) related to genera of mite-infecting plant viruses (Blunervirus, Cilevirus, and Higrevirus) in the new family Kitaviridae [49, 73] , or novel members of Entomobirnavirus, family Birnaviridae ( Figure 10D ). abstract: Since the beginning of modern virology in the 1950s, transmission electron microscopy (TEM) has been an important and widely used technique for discovery, identification and characterization of new viruses. Using TEM, viruses can be differentiated by their ultrastructure: shape, size, intracellular location and for some viruses, by the ultrastructural cytopathic effects and/or specific structures forming in the host cell during their replication. Ultrastructural characteristics are usually sufficient for the identification of a virus to the family level. In this review, we summarize 25 years of experience in identification of novel viruses from the collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA). url: https://doi.org/10.3390/v11050477 doi: 10.3390/v11050477 id: cord-267012-45tre8rn author: Premanand, Balraj title: Baculovirus Surface Display of Immunogenic Proteins for Vaccine Development date: 2018-05-31 words: 11102.0 sentences: 530.0 pages: flesch: 34.0 cache: ./cache/cord-267012-45tre8rn.txt txt: ./txt/cord-267012-45tre8rn.txt summary: While recombinant baculoviral vector expressing both VSV-G and influenza HA was shown to evoke both humoral and cellular immune responses and provided effective protection against lethal virus challenge in mouse and chicken hosts [26] , the high cytotoxicity of VSV-G protein [98] and its immediate inactivation by serum complement systems impedes the use of the element in a vaccine delivery vehicle [99] . The vaccine showed successful HA expression on its envelope, and mice vaccination studies showed that both the live and adjuvanted with inactive form of recombinant baculovirus induced HA-specific antibody responses and offered complete protection against lethal viral infection [101] . Moreover, recombinant baculovirus with CMV-polyhedrin dual promoter for expressing chimeric HA of H9N2 was shown to efficiently express HA in both mammalian and insect cells, induce strong immune response, and provide 100% protection against lethal H9N2 viral challenge in mice, unlike other vaccine candidates observed [34] . abstract: Vaccination is an efficient way to prevent the occurrence of many infectious diseases in humans. To date, several viral vectors have been utilized for the generation of vaccines. Among them, baculovirus—categorized as a nonhuman viral vector—has been used in wider applications. Its versatile features, like large cloning capacity, nonreplicative nature in mammalian cells, and broad tissue tropism, hold it at an excellent position among vaccine vectors. In addition to ease and safety during swift production, recent key improvements to existing baculovirus vectors (such as inclusion of hybrid promoters, immunostimulatory elements, etc.) have led to significant improvements in immunogenicity and efficacy of surface-displayed antigens. Furthermore, some promising preclinical results have been reported that mirror the scope and practicality of baculovirus as a vaccine vector for human applications in the near future. Herein, this review provides an overview of the induced immune responses by baculovirus surface-displayed vaccines against influenza and other infectious diseases in animal models, and highlights the strategies applied to enhance the protective immune responses against the displayed antigens. url: https://doi.org/10.3390/v10060298 doi: 10.3390/v10060298 id: cord-342130-eo4le4v3 author: Qin, Pan title: Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy date: 2019-05-18 words: 4029.0 sentences: 209.0 pages: flesch: 46.0 cache: ./cache/cord-342130-eo4le4v3.txt txt: ./txt/cord-342130-eo4le4v3.txt summary: title: Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy PDCoV infection also increased the number of autophagosome-like vesicles in the cytoplasm of cells, and the autophagy response was detected by LC3 I/II and p62 Western blot analysis. Double-membraned autophagosomes-like vesicles were detected in PDCoV-infected cells at 12 hpi and increased thereafter. In summary, we demonstrate and elaborate some novel, in vitro characteristics of the life cycle of PDCoV, including replication kinetics in cultured cells, cellular ultrastructure, virion morphology, and possible induction of autophagy, mainly by means of EM observation. In summary, we demonstrate and elaborate some novel, in vitro characteristics of the life cycle of PDCoV, including replication kinetics in cultured cells, cellular ultrastructure, virion morphology, and possible induction of autophagy, mainly by means of EM observation. abstract: Porcine deltacoronavirus (PDCoV) causes severe diarrhea and vomiting in affected piglets. The aim of this study was to establish the basic, in vitro characteristics of the life cycle such as replication kinetics, cellular ultrastructure, virion morphology, and induction of autophagy of PDCoV. Time-course analysis of viral subgenomic and genomic RNA loads and infectious titers indicated that one replication cycle of PDCoV takes 5 to 6 h. Electron microscopy showed that PDCoV infection induced the membrane rearrangements with double-membrane vesicles and large virion-containing vacuoles. The convoluted membranes structures described in alpha- and beta-coronavirus were not observed. PDCoV infection also increased the number of autophagosome-like vesicles in the cytoplasm of cells, and the autophagy response was detected by LC3 I/II and p62 Western blot analysis. For the first time, this study presents the picture of the PDCoV infection cycle, which is crucial to help elucidate the molecular mechanism of deltacoronavirus replication. url: https://www.ncbi.nlm.nih.gov/pubmed/31109068/ doi: 10.3390/v11050455 id: cord-295750-0gpyi4ii author: Raev, Sergei title: An Outbreak of a Respiratory Disorder at a Russian Swine Farm Associated with the Co-Circulation of PRRSV1 and PRRSV2 date: 2020-10-15 words: 2937.0 sentences: 331.0 pages: flesch: 59.0 cache: ./cache/cord-295750-0gpyi4ii.txt txt: ./txt/cord-295750-0gpyi4ii.txt summary: A partial open reading frame 7 sequence of the PRRSV2 isolate demonstrated a high identity with modified live vaccine-related strains from Denmark (93%) and wild-type VR2332 (92%). PRRSV, PCV2, swine influenza virus (SIV), porcine parvovirus virus (PPV), and porcine respiratory coronavirus (PRCV) in serum samples were detected using commercial polymerase chain reaction (PCR) kits (Vetbiochem, Russia) according to the manufacturer''s instructions. Phylogenetic analysis of a partial ORF7 sequence of the PRRSV2 strain isolated in the course of this study revealed that this strain was very dissimilar (88% identity) to the only known PRRSV2 strain (JXA1-related, sublineage 8.7) detected in East Siberia, Russia, in 2007. Comparison of Molecular and Biological Characteristics of a Modified Live Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Vaccine (Ingelvac PRRS MLV), the Parent Strain of the Vaccine (ATCC VR2332), ATCC VR2385, and Two Recent Field Isolates of PRRSV Genetic Analysis of ORF5 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Isolated in Vietnam abstract: We conducted a cross-sectional study to identify the major respiratory pathogen responsible for an outbreak of respiratory disease at a swine farm in West Siberia in 2019. We discovered that the peak of morbidity and mortality coincided with a high level of porcine reproductive and respiratory syndrome virus (PRRSV) 1 and 2-related viremia. Based on longer PRRSV2 viremia, the dominant role of PRRSV2 over PRRSV1 in the outbreak was assumed. Phylogenetic analysis revealed that the PRRSV1 strain belonged to sub-genotype 2—one of the predominant groups of genotype 1 PRRSVs in Russia. A partial open reading frame 7 sequence of the PRRSV2 isolate demonstrated a high identity with modified live vaccine-related strains from Denmark (93%) and wild-type VR2332 (92%). We identified the first instance of PRRSV1/PRRSV2 mixed infection in Russia. This finding indicates that further field investigations are needed to access PRRSV2 epidemiology in eastern Europe. url: https://www.ncbi.nlm.nih.gov/pubmed/33076391/ doi: 10.3390/v12101169 id: cord-002590-24o2viv3 author: Rahe, Michael C. title: Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus date: 2017-06-13 words: 8016.0 sentences: 375.0 pages: flesch: 34.0 cache: ./cache/cord-002590-24o2viv3.txt txt: ./txt/cord-002590-24o2viv3.txt summary: Pig immune response to general stimulus and to porcine reproductive and respiratory syndrome virus infection: A meta-analysis approach Antigen-specific B-cell responses to porcine reproductive and respiratory syndrome virus infection The Chinese highly pathogenic porcine reproductive and respiratory syndrome virus infection suppresses Th17 cells response in vivo Pathogenic and humoral immune responses to porcine reproductive and respiratory syndrome virus (PRRSV) are related to viral load in acute infection Porcine reproductive and respiratory syndrome virus-infected alveolar macrophages contain no detectable levels of viral proteins in their plasma membrane and are protected against antibody-dependent, complement-mediated cell lysis Polyclonal activation of B cells occurs in lymphoid organs from porcine reproductive and respiratory syndrome virus (PRRSV)-infected pigs The role of porcine reproductive and respiratory syndrome virus infection in immune phenotype and Th1/Th2 balance of dendritic cells Porcine reproductive and respiratory syndrome virus induces pronounced immune modulatory responses at mucosal tissues in the parental vaccine strain VR2332 infected pigs abstract: The adaptive immune response is necessary for the development of protective immunity against infectious diseases. Porcine reproductive and respiratory syndrome virus (PRRSV), a genetically heterogeneous and rapidly evolving RNA virus, is the most burdensome pathogen of swine health and wellbeing worldwide. Viral infection induces antigen-specific immunity that ultimately clears the infection. However, the resulting immune memory, induced by virulent or attenuated vaccine viruses, is inconsistently protective against diverse viral strains. The immunological mechanisms by which primary and memory protection are generated and used are not well understood. Here, we summarize current knowledge regarding cellular and humoral components of the adaptive immune response to PRRSV infection that mediate primary and memory immune protection against viruses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490824/ doi: 10.3390/v9060148 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-001887-d6ycc8ci author: Romero-Brey, Inés title: Viral Infection at High Magnification: 3D Electron Microscopy Methods to Analyze the Architecture of Infected Cells date: 2015-12-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: As obligate intracellular parasites, viruses need to hijack their cellular hosts and reprogram their machineries in order to replicate their genomes and produce new virions. For the direct visualization of the different steps of a viral life cycle (attachment, entry, replication, assembly and egress) electron microscopy (EM) methods are extremely helpful. While conventional EM has given important information about virus-host cell interactions, the development of three-dimensional EM (3D-EM) approaches provides unprecedented insights into how viruses remodel the intracellular architecture of the host cell. During the last years several 3D-EM methods have been developed. Here we will provide a description of the main approaches and examples of innovative applications. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690864/ doi: 10.3390/v7122940 id: cord-294842-aesiff1f author: Romero-Brey, Inés title: Membranous Replication Factories Induced by Plus-Strand RNA Viruses date: 2014-07-22 words: 11038.0 sentences: 520.0 pages: flesch: 40.0 cache: ./cache/cord-294842-aesiff1f.txt txt: ./txt/cord-294842-aesiff1f.txt summary: Three-dimensional reconstructions of the WNV KUN replication sites revealed an intimate association of the rough ER (rER) with the bounding membrane of the VPs [20] (Figure 2B ), resembling the vesicles observed in DENV-infected cells. In cells infected with TBEV, one of the most important tick-transmitted viruses in Europe and Asia, virus particles and membrane-connected vesicles were also observed inside the ER [25] , similar to what was described for DENV and WNV KUN . Importantly, pulse-radiolabeling experiments localized sites of active RNA replication to the outer surface of single-membrane tubules [71] and isolation of the membranous replication factories and their subsequent visualization by EM revealed that they form rosette-like structures composed of virus-induced cytoplasmic vesicles [124] . Formation of plant RNA virus replication complexes on membranes: Role of an endoplasmic reticulum-targeted viral protein abstract: In this review, we summarize the current knowledge about the membranous replication factories of members of plus-strand (+) RNA viruses. We discuss primarily the architecture of these complex membrane rearrangements, because this topic emerged in the last few years as electron tomography has become more widely available. A general denominator is that two “morphotypes” of membrane alterations can be found that are exemplified by flaviviruses and hepaciviruses: membrane invaginations towards the lumen of the endoplasmatic reticulum (ER) and double membrane vesicles, representing extrusions also originating from the ER, respectively. We hypothesize that either morphotype might reflect common pathways and principles that are used by these viruses to form their membranous replication compartments. url: https://doi.org/10.3390/v6072826 doi: 10.3390/v6072826 id: cord-001831-3aonqyub author: Royle, Jamie title: Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals? date: 2015-10-16 words: 6390.0 sentences: 311.0 pages: flesch: 42.0 cache: ./cache/cord-001831-3aonqyub.txt txt: ./txt/cord-001831-3aonqyub.txt summary: Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention. Research over recent decades has identified a group of virus-encoded proteins able to mediate the passage of ions and solutes across cellular membranes, termed viroporins [1, 2] . Due to these broad perturbations to host cell physiology, it is not surprising that viroporin function has been shown to assist in all stages of the virus life cycle including entry, membrane penetration, genome replication and virus egress [1, 2] . This review will summarize our understanding of these putative viroporins, describe their known functions and attempt to highlight how possible ion channel activity may aid the life cycles of these small DNA tumor viruses. abstract: Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. These viroporins mediate the flow of ions and a range of solutes across cellular membranes and are necessary for manipulating a myriad of host processes. As such they contribute to all stages of the virus life cycle. Recent discoveries have identified proteins encoded by the small DNA tumor viruses that display a number of viroporin like properties. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632388/ doi: 10.3390/v7102880 id: cord-332165-31tbc31x author: Rustmeier, Nils H. title: The Symmetry of Viral Sialic Acid Binding Sites—Implications for Antiviral Strategies date: 2019-10-14 words: 5820.0 sentences: 316.0 pages: flesch: 43.0 cache: ./cache/cord-332165-31tbc31x.txt txt: ./txt/cord-332165-31tbc31x.txt summary: In this review, we will evaluate the structures of non-enveloped virus capsid proteins bound to sialylated glycan receptors and discuss the potential of these structures for the development of potent antiviral attachment inhibitors. This concept of targeting multiple, symmetric receptor binding sites by multivalent inhibitors is also applicable for many viruses, since viral capsids are often icosahedral and, therefore, highly symmetric structures. Many members of the polyomavirus family bind sialic acid-based glycans using their VP1 proteins, so the binding sites on individual pentamers are always linked by local five-fold symmetry (Figure 4a , TSPyV). The glycooligopeptide-VP1 complex structures displayed a similar ligand binding mode that was reported for sialic acid in an earlier study [50] and showed, for the compounds, that the linker between the ligand and the scaffold occupies the space that is usually targeted by the natural glycan receptor moieties (Figure 5a,b, right) . abstract: Virus infections are initiated by the attachment of the viral particle to protein or carbohydrate receptors on the host cell. Sialic acid-bearing glycan structures are prominently displayed at the cell surface, and, consequently, these structures can function as receptors for a large number of diverse viruses. Structural biology research has helped to establish the molecular bases for many virus–sialic acid interactions. Due to the icosahedral 532 point group symmetry that underlies many viral capsids, the receptor binding sites are frequently arranged in a highly symmetric fashion and linked by five-fold, three-fold, or two-fold rotation axes. For the inhibition of viral attachment, one emerging strategy is based on developing multivalent sialic acid-based inhibitors that can simultaneously engage several of these binding sites, thus binding viral capsids with high avidity. In this review, we will evaluate the structures of non-enveloped virus capsid proteins bound to sialylated glycan receptors and discuss the potential of these structures for the development of potent antiviral attachment inhibitors. url: https://www.ncbi.nlm.nih.gov/pubmed/31615155/ doi: 10.3390/v11100947 id: cord-309378-sfr1x0ob author: Röst, Gergely title: Early Phase of the COVID-19 Outbreak in Hungary and Post-Lockdown Scenarios date: 2020-06-30 words: 10526.0 sentences: 585.0 pages: flesch: 57.0 cache: ./cache/cord-309378-sfr1x0ob.txt txt: ./txt/cord-309378-sfr1x0ob.txt summary: COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a considerable reduction in the number of contacts and transmission of the virus. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed. Moreover, closing schools postpones the peak of the epidemic (by about one month in case of the above setting), suggesting that children may play a significant role in transmission due to their large number of contacts, even though they give negligible contribution to the overall mortality, cf. As control measures are being successively relaxed since May 4, we established an age-structured compartmental model to investigate several post-lockdown scenarios, and projected the epidemic curves and the demand for critical care beds assuming various levels of sustained reduction in transmission. abstract: COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a considerable reduction in the number of contacts and transmission of the virus. This strategy was effective in preventing epidemic growth and reducing the incidence of COVID-19 to low levels. In this report, we present the first epidemiological and statistical analysis of the early phase of the COVID-19 outbreak in Hungary. Then, we establish an age-structured compartmental model to explore alternative post-lockdown scenarios. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed. url: https://doi.org/10.3390/v12070708 doi: 10.3390/v12070708 id: cord-273326-gmw8gl2r author: Saiz, Juan-Carlos title: Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus date: 2018-08-24 words: 7111.0 sentences: 293.0 pages: flesch: 34.0 cache: ./cache/cord-273326-gmw8gl2r.txt txt: ./txt/cord-273326-gmw8gl2r.txt summary: In this line, and contrary to above mentioned report [73] , CQ, an FDA-approved anti-inflammatory 4-aminoquinoline and an autophagy inhibitor widely used as an anti-malaria drug that is administered to pregnant women at risk of exposure to Plasmodium parasites, was shown to have anti-ZIKV activity in different cell types (Vero cells, human brain microvascular endothelial cells (hBMECs), and human neural stem cells (NSCs)), affecting early stages of the viral life cycle, possibly by raising the endosomal pH and inhibiting the fusion of the envelope protein to the endosomal membrane [74, 75] . Similarly, by using a drug repurposing screening of over 6000 molecules, it was found that emricasan, a pan-caspase inhibitor that restrains ZIKV-induced increases in caspase-3 activity and is currently in phase 2 clinical trials in chronic hepatitis C virus (HCV)-infected patients, protected human cortical neural progenitor cells (NPC) in both monolayer and three-dimensional organoid cultures, showing neuroprotective activity without suppression of viral replication [82] . abstract: Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, search for antivirals has been a major aim in ZIKV investigations. To do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection. url: https://www.ncbi.nlm.nih.gov/pubmed/30149598/ doi: 10.3390/v10090453 id: cord-296819-gztmidn2 author: Sambri, Vittorio title: Diagnosis of West Nile Virus Human Infections: Overview and Proposal of Diagnostic Protocols Considering the Results of External Quality Assessment Studies date: 2013-09-25 words: 6732.0 sentences: 304.0 pages: flesch: 42.0 cache: ./cache/cord-296819-gztmidn2.txt txt: ./txt/cord-296819-gztmidn2.txt summary: title: Diagnosis of West Nile Virus Human Infections: Overview and Proposal of Diagnostic Protocols Considering the Results of External Quality Assessment Studies This paper reviews the presently available methods to achieve the laboratory diagnosis of West Nile virus infections in humans, discussing the most prominent advantages and disadvantages of each in light of the results obtained during four different External Quality Assessment studies carried out by the European Network for ''Imported'' Viral Diseases (ENIVD). For the routine detection of WNV RNA using molecular techniques there are two distinct diagnostic settings: the first involves blood and organ donation screening from subjects living in an area where WNV circulation is known to be occurring, and the second involves the identification of viral genomes in serum, plasma and CSF samples from patients presenting with a clinical picture typical of WNV infection [21] . abstract: West Nile virus, genus Flavivirus, is transmitted between birds and occasionally other animals by ornithophilic mosquitoes. This virus also infects humans causing asymptomatic infections in about 85% of cases and <1% of clinical cases progress to severe neuroinvasive disease. The virus also presents a threat since most infections remain unapparent. However, the virus contained in blood and organs from asymptomatically infected donors can be transmitted to recipients of these infectious tissues. This paper reviews the presently available methods to achieve the laboratory diagnosis of West Nile virus infections in humans, discussing the most prominent advantages and disadvantages of each in light of the results obtained during four different External Quality Assessment studies carried out by the European Network for ‘Imported’ Viral Diseases (ENIVD). url: https://www.ncbi.nlm.nih.gov/pubmed/24072061/ doi: 10.3390/v5102329 id: cord-297834-me1ajoyb author: Schountz, Tony title: Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions date: 2014-03-14 words: 6425.0 sentences: 334.0 pages: flesch: 38.0 cache: ./cache/cord-297834-me1ajoyb.txt txt: ./txt/cord-297834-me1ajoyb.txt summary: The immune response is energetically expensive for wild animals, thus the findings of experimental studies will be critical for understanding the ecoimmunology of reservoir hosts of hantaviruses [6, 7] , and experiments using wild rodents in natural or semi-natural environments [8, 9] will be required to validate laboratory findings. Currently, three laboratory infection systems have been developed to study hantavirus infections of reservoir hosts: Seoul virus (SEOV) infection of the Norway rat (Rattus norvegicus), Puumala virus (PUUV) infection of the bank vole (Myodes glareolus), and Sin Nombre virus (SNV) infection of the deer mouse (Peromyscus maniculatus) [12, 14, 16] . Experimental data have also shown that patterns of the expression of genes related to the immune response are different in infected males and females [32] , and it is likely these differences have important roles in hantavirus ecology. abstract: Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships. url: https://www.ncbi.nlm.nih.gov/pubmed/24638205/ doi: 10.3390/v6031317 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: 15685.0 sentences: 761.0 pages: flesch: 38.0 cache: ./cache/cord-012418-6ralcn8p.txt txt: ./txt/cord-012418-6ralcn8p.txt summary: 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. The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ). The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ). 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-342739-iy9vjpuh author: Schwartz, David A. title: Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections date: 2020-02-10 words: 8414.0 sentences: 406.0 pages: flesch: 49.0 cache: ./cache/cord-342739-iy9vjpuh.txt txt: ./txt/cord-342739-iy9vjpuh.txt summary: In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. The most common adverse obstetrical outcomes associated with maternal pneumonias from all causes include This newly recognized coronavirus, producing a disease that has been termed COVID-19, is rapidly spreading throughout China, has crossed international borders to infect persons in neighboring countries, and humans infected by the virus are travelling via commercial airlines to other continents. Pregnant women may develop severe disease and fatal maternal and/or fetal outcomes as a result of MERS-CoV infection; however, little is known of the pathophysiology of this infection during pregnancy. abstract: In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, initially termed 2019-nCoV and subsequently SARS-CoV-2. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines. url: https://doi.org/10.3390/v12020194 doi: 10.3390/v12020194 id: cord-345472-qrddwebe author: Sebina, Ismail title: The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis date: 2020-07-27 words: 8184.0 sentences: 411.0 pages: flesch: 28.0 cache: ./cache/cord-345472-qrddwebe.txt txt: ./txt/cord-345472-qrddwebe.txt summary: A vaccine against respiratory syncytial virus (RSV), the leading cause of viral bronchiolitis in infancy, remains elusive, and hence new therapeutic modalities are needed to limit disease severity. (1), degranulation (2), respiratory oxygen species (ROS) production (3), and the release of neutrophil extracellular traps (NETosis) (4) are associated with increased lung inflammation, systemic fever, mucus hypersecretion, airway obstruction, and epithelial cell death. Excessive neutrophil-derived inflammatory cytokine production (1), degranulation (2), respiratory oxygen species (ROS) production (3), and the release of neutrophil extracellular traps (NETosis) (4) are associated with increased lung inflammation, systemic fever, mucus hypersecretion, airway obstruction, and epithelial cell death. Unlike wild-type (WT) control mice, plasmacytoid dendritic cell (pDC)-depleted, Toll-like receptor (TLR)7-deficient, or interferon regulatory factor (IRF)7-deficient neonatal mice develop severe pathology, characterised by increased neutrophilia and lung inflammation in response to acute PVM infection [80] [81] [82] . abstract: Acute viral bronchiolitis causes significant mortality in the developing world, is the number one cause of infant hospitalisation in the developed world, and is associated with the later development of chronic lung diseases such as asthma. A vaccine against respiratory syncytial virus (RSV), the leading cause of viral bronchiolitis in infancy, remains elusive, and hence new therapeutic modalities are needed to limit disease severity. However, much remains unknown about the underlying pathogenic mechanisms. Neutrophilic inflammation is the predominant phenotype observed in infants with both mild and severe disease, however, a clear understanding of the beneficial and deleterious effects of neutrophils is lacking. In this review, we describe the multifaceted roles of neutrophils in host defence and antiviral immunity, consider their contribution to bronchiolitis pathogenesis, and discuss whether new approaches that target neutrophil effector functions will be suitable for treating severe RSV bronchiolitis. url: https://doi.org/10.3390/v12080808 doi: 10.3390/v12080808 id: cord-004510-cbutpjre author: Seetahal, Janine F. R. title: The Serological Prevalence of Rabies Virus-Neutralizing Antibodies in the Bat Population on the Caribbean Island of Trinidad date: 2020-02-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Rabies virus (RABV) is the only lyssavirus known to be present within the Caribbean. The island of Trinidad, is richly diverse in chiropteran fauna and endemic for bat-transmitted rabies with low RABV isolation rates observed in this population. We aimed to determine the seroprevalence of rabies virus neutralizing antibodies (RVNA) in light of spatio-temporal and bat demographic factors to infer the extent of natural exposure to RABV in the Trinidadian bat population. RVNA titers were determined by the RABV micro-neutralization test on 383 bat samples representing 21 species, comprising 30.9% of local bat diversity, from 31 locations across the island over 5 years. RVNA was positively detected in 33 samples (8.6%) representing 6 bat species (mainly frugivorous) with titers ranging from 0.1 to 19 IU/mL (mean 1.66 IU/mL). The analyses based on a multivariable binomial generalised linear mixed-effects model showed that bat age and year of capture were significant predictors of seropositivity. Thus, juvenile bats were more likely to be seropositive when compared to adults (estimate 1.13; p = 0.04) which may suggest early exposure to the RABV with possible implications for viral amplification in this population. Temporal variation in rabies seropositivity, 2012–2014 versus 2015–2017 (estimate 1.07; p = 0.03) may have been related to the prevailing rabies epizootic situation. Regarding other factors investigated, RVNA was found in bats from both rural and non-rural areas, as well as in both hematophagous and non-hematophagous bat species. The most common seropositive species, Artibeus jamaicensis planirostris is ubiquitous throughout the island which may potentially facilitate human exposure. The findings of this study should be factored into public health assessments on the potential for rabies transmission by non-hematophagous bats in Trinidad. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077287/ doi: 10.3390/v12020178 id: cord-260476-whfyczcj author: Seissler, Tanja title: Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins date: 2017-10-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ubiquitin-proteasome system (UPS) ensures regulation of the protein pool in the cell by ubiquitination of proteins followed by their degradation by the proteasome. It plays a central role in the cell under normal physiological conditions as well as during viral infections. On the one hand, the UPS can be used by the cell to degrade viral proteins, thereby restricting the viral infection. On the other hand, it can also be subverted by the virus to its own advantage, notably to induce degradation of cellular restriction factors. This makes the UPS a central player in viral restriction and counter-restriction. In this respect, the human immunodeficiency viruses (HIV-1 and 2) represent excellent examples. Indeed, many steps of the HIV life cycle are restricted by cellular proteins, some of which are themselves components of the UPS. However, HIV itself hijacks the UPS to mediate defense against several cellular restriction factors. For example, the HIV auxiliary proteins Vif, Vpx and Vpu counteract specific restriction factors by the recruitment of cellular UPS components. In this review, we describe the interplay between HIV and the UPS to illustrate its role in the restriction of viral infections and its hijacking by viral proteins for counter-restriction. url: https://www.ncbi.nlm.nih.gov/pubmed/29088112/ doi: 10.3390/v9110322 id: cord-330475-mameyzih author: Shi, Da title: Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus date: 2014-03-13 words: 5570.0 sentences: 296.0 pages: flesch: 44.0 cache: ./cache/cord-330475-mameyzih.txt txt: ./txt/cord-330475-mameyzih.txt summary: Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. The B23.1-DsRed fusion protein was used to tag the nucleolus, so we could analyze nucleolar localization properties and colocalization in cotransfected cells by live cell imaging (direct fluorescence) or confocal microscopy. These expression plasmids were transfected into Vero E6 cells, the nuclear was stained with DAPI at 24 h post-transfection indicated that amino acids 148-220 directed AcGFP to the cytoplasm and nucleus and had a subcellular localization similar to AcGFP. abstract: The nucleolus is a dynamic subnuclear structure, which is crucial to the normal operation of the eukaryotic cell. The porcine epidemic diarrhea virus (PEDV), coronavirus nucleocapsid (N) protein, plays important roles in the process of virus replication and cellular infection. Virus infection and transfection showed that N protein was predominately localized in the cytoplasm, but also found in the nucleolus in Vero E6 cells. Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. We also identified two nuclear export signals (NES, aa221–236, and 325–364), however, only the nuclear export signal (aa325–364) was found to be functional in the context of the full-length N protein. Finally, the activity of this nuclear export signal (NES) was inhibited by the antibiotic Lepomycin B, suggesting that N is exported by a chromosome region maintenance 1-related export pathway. url: https://www.ncbi.nlm.nih.gov/pubmed/24632575/ doi: 10.3390/v6031253 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: 4090.0 sentences: 202.0 pages: flesch: 34.0 cache: ./cache/cord-270103-g9a72xf6.txt txt: ./txt/cord-270103-g9a72xf6.txt summary: 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. Some nucleoside analog drugs targeting specific viral polymerases (acyclovir for herpesviruses, zidovudine for human immunodeficiency virus (HIV), and sofosbuvir for hepatitis C virus (HCV)) have been successful in clinical trials [2] [3] [4] [5] and are currently in use for the treatment of virus-infected patients. However, in recent years, the antiviral activity of gemcitabine has also been reported against a broad range of RNA viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), HCV, poliovirus (PV), influenza A virus (IAV), HIV, and enteroviruses (EV) [13] [14] [15] [16] [17] [18] . Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion 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-254181-nquozaxt author: Sieg, Michael title: A New Genotype of Feline Morbillivirus Infects Primary Cells of the Lung, Kidney, Brain and Peripheral Blood date: 2019-02-09 words: 8567.0 sentences: 434.0 pages: flesch: 50.0 cache: ./cache/cord-254181-nquozaxt.txt txt: ./txt/cord-254181-nquozaxt.txt summary: To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. To elucidate the target tissues of FeMV-GT2 we established protocols for the isolation of primary feline cells from various organs of cats (see section 2.2.) Experimental in vitro infection was performed using the LLC-MK2-adapted FeMV-GT2-Gordon strain. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. To elucidate the involvement of adjacent organs in virus shedding, primary feline bladder epithelial cells were isolated and infected with FeMV-GT2 as described above. abstract: Paramyxoviruses comprise a large number of diverse viruses which in part give rise to severe diseases in affected hosts. A new genotype of feline morbillivirus, tentatively named feline morbillivirus genotype 2 (FeMV-GT2), was isolated from urine of cats with urinary tract diseases. Whole genome sequencing showed about 78% nucleotide homology to known feline morbilliviruses. The virus was isolated in permanent cell lines of feline and simian origin. To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. We demonstrate that FeMV-GT2 is able to infect renal and pulmonary epithelial cells, primary cells from the cerebrum and cerebellum, as well as immune cells in the blood, especially CD4(+) T cells, CD20(+) B cells and monocytes. The cats used for virus isolation shed FeMV-GT2 continuously for several months despite the presence of neutralizing antibodies in the blood. Our results point towards the necessity of increased awareness for this virus when clinical signs of the aforementioned organs are encountered in cats which cannot be explained by other etiologies. url: https://www.ncbi.nlm.nih.gov/pubmed/30744110/ doi: 10.3390/v11020146 id: cord-283756-ycjzitlk author: Simons, Robin R. L. title: Potential for Introduction of Bat-Borne Zoonotic Viruses into the EU: A Review date: 2014-05-16 words: 14415.0 sentences: 605.0 pages: flesch: 53.0 cache: ./cache/cord-283756-ycjzitlk.txt txt: ./txt/cord-283756-ycjzitlk.txt summary: Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. Bats are known to have varying degrees of contact with domestic animals and commercial food crops [20, 21] , in particular contact of Pteropus giganteus bats with date palm sap producing trees in Bangladesh is considered a risk factor for human NiV infection [22] . It can be seen that while recent human infections of both NiV and MARV appear to be limited in geographical range (the red areas in Figure 2 ), there are a number of countries where bats have been identified as having the virus, but no human infection has been reported. abstract: Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. To date, significant human outbreaks of such viruses have not been reported in the European Union (EU). However, EU countries have strong historical links with many of the countries where NiV and MARV are present and a corresponding high volume of commercial trade and human travel, which poses a potential risk of introduction of these viruses into the EU. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. In this paper, we review the current scientific knowledge of all these factors, in relation to the introduction of NiV and MARV into the EU. url: https://doi.org/10.3390/v6052084 doi: 10.3390/v6052084 id: cord-284216-4sl8xfur author: Sinha, Anirban title: Can Measurements of Inflammatory Biomarkers Be Used to Spot Respiratory Viral Infections? date: 2020-10-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Accurate detection of human respiratory viral infections is highly topical. We investigated how strongly inflammatory biomarkers (FeNO, eosinophils, neutrophils, and cytokines in nasal lavage fluid) and lung function parameters change upon rhinovirus 16 infection, in order to explore their potential use for infection detection. To this end, within a longitudinal cohort study, healthy and mildly asthmatic volunteers were experimentally inoculated with rhinovirus 16, and time series of these parameters/biomarkers were systematically recorded and compared between the pre- and post-infection phases of the study, which lasted two months and one month, respectively. We found that the parameters’/biomarkers’ ability to discriminate between the infected and the uninfected state varied over the observation time period. Consistently over time, the concentration of cytokines, in nasal lavage fluid, showed moderate to very good discrimination performance, thereby qualifying for disease progression monitoring, whereas lung function and FeNO, while quickly and non-invasively measurable using cheap portable devices (e.g., at airports), performed poorly. url: https://doi.org/10.3390/v12101175 doi: 10.3390/v12101175 id: cord-300625-fvirvpyl author: Srinivasan, Suhas title: Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins date: 2020-03-25 words: 5902.0 sentences: 285.0 pages: flesch: 41.0 cache: ./cache/cord-300625-fvirvpyl.txt txt: ./txt/cord-300625-fvirvpyl.txt summary: In addition to the global structural genomics, an initiative that focuses on determining the 3D structures of individual proteins on a genome scale [34] , as well as to the specific efforts aimed at rapid structural characterization of proteins in emerging viruses [35] [36] [37] [38] , multiple works have used comparative modeling to predict the structures of protein-protein interaction complexes [39] [40] [41] , facilitate structure-based drug discovery [33, 42, 43] , infer protein functions [44] , determine the macromolecular interaction network [45] [46] [47] [48] , and provide molecular insights into the viral evolution [49] [50] [51] . To do so, we structurally characterized individual proteins as well as intra-viral and human-virus protein complexes, extracted the information on their interaction interfaces and ligand binding, and superposed the evolutionary difference and conservation information with the binding information. abstract: During its first two and a half months, the recently emerged 2019 novel coronavirus, SARS-CoV-2, has already infected over one-hundred thousand people worldwide and has taken more than four thousand lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge, we leveraged data about the related coronaviruses that is readily available in public databases and integrated these data into a single computational pipeline. As a result, we provide comprehensive structural genomics and interactomics roadmaps of SARS-CoV-2 and use this information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community. url: https://www.ncbi.nlm.nih.gov/pubmed/32218151/ doi: 10.3390/v12040360 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-338589-1ent68fx author: Stoddard, Shana V. title: Optimization Rules for SARS-CoV-2 M(pro) Antivirals: Ensemble Docking and Exploration of the Coronavirus Protease Active Site date: 2020-08-26 words: 11437.0 sentences: 606.0 pages: flesch: 55.0 cache: ./cache/cord-338589-1ent68fx.txt txt: ./txt/cord-338589-1ent68fx.txt summary: The ensemble docking and characterization work described in this article demonstrates the multifaceted features of the SARS-CoV-2 M(pro) active site, molecular guidelines to improving binding affinity, and ultimately the optimization of drug candidates. After optimization efforts using the design guidelines developed from the molecular docking studies, the average docking score of the parent compounds was improved by 6.59 −log(10)(Kd) in binding affinity which represents an increase of greater than six orders of magnitude. The results of molecular dynamic (MD) simulation of cinanserin-optimized compounds CM02, CM06, and CM07 revealed that CM02 and CM06 fit well into the active site of SARS-CoV-2 M(pro) [Protein Data Bank (PDB) accession number 6LU7] and formed strong and stable interactions with the key residues, Ser-144, His-163, and Glu-166. The use of multiple conformations when using docking will assist in the prediction of new antivirals agents targeting SARS-CoV-2 M pro as the diversity of accessible variations can produce distinct binding poses for an inhibitor compound. abstract: Coronaviruses are viral infections that have a significant ability to impact human health. Coronaviruses have produced two pandemics and one epidemic in the last two decades. The current pandemic has created a worldwide catastrophe threatening the lives of over 15 million as of July 2020. Current research efforts have been focused on producing a vaccine or repurposing current drug compounds to develop a therapeutic. There is, however, a need to study the active site preferences of relevant targets, such as the SARS-CoV-2 main protease (SARS-CoV-2 M(pro)), to determine ways to optimize these drug compounds. The ensemble docking and characterization work described in this article demonstrates the multifaceted features of the SARS-CoV-2 M(pro) active site, molecular guidelines to improving binding affinity, and ultimately the optimization of drug candidates. A total of 220 compounds were docked into both the 5R7Z and 6LU7 SARS-CoV-2 M(pro) crystal structures. Several key preferences for strong binding to the four subsites (S1, S1′, S2, and S4) were identified, such as accessing hydrogen binding hotspots, hydrophobic patches, and utilization of primarily aliphatic instead of aromatic substituents. After optimization efforts using the design guidelines developed from the molecular docking studies, the average docking score of the parent compounds was improved by 6.59 −log(10)(Kd) in binding affinity which represents an increase of greater than six orders of magnitude. Using the optimization guidelines, the SARS-CoV-2 M(pro) inhibitor cinanserin was optimized resulting in an increase in binding affinity of 4.59 −log(10)(Kd) and increased protease inhibitor bioactivity. The results of molecular dynamic (MD) simulation of cinanserin-optimized compounds CM02, CM06, and CM07 revealed that CM02 and CM06 fit well into the active site of SARS-CoV-2 M(pro) [Protein Data Bank (PDB) accession number 6LU7] and formed strong and stable interactions with the key residues, Ser-144, His-163, and Glu-166. The enhanced binding affinity produced demonstrates the utility of the design guidelines described. The work described herein will assist scientists in developing potent COVID-19 antivirals. url: https://doi.org/10.3390/v12090942 doi: 10.3390/v12090942 id: cord-012420-llh22iq2 author: Stott, Robert J. title: Distinct Molecular Mechanisms of Host Immune Response Modulation by Arenavirus NP and Z Proteins date: 2020-07-21 words: 12015.0 sentences: 579.0 pages: flesch: 41.0 cache: ./cache/cord-012420-llh22iq2.txt txt: ./txt/cord-012420-llh22iq2.txt summary: Interestingly, non-pathogenic OW Mopeia virus (MOPV), a close genetic relative to LASV, induces a strong initial IFN and cytokine response in infected moDCs and macrophages leading to a sustained T cell activation and immune response [67, 68] . Similar to NP, interaction of arenavirus Z proteins with RIG-I prevents further binding to MAVS and therefore inhibits the production of IFN-β and reduces antiviral host immune responses. Although the inhibition of RIG-I signalling by highly pathogenic arenaviruses in vitro suggests that there should be limited IFN1 response, it is notable that in vivo infection with some of these viruses (LCMV, JUNV) induces high levels of IFN1, ISGs and cytokines suggesting that this strategy is not completely effective or is widely varied in cell type and differs from host to host [134, 135, 186] . abstract: Endemic to West Africa and South America, mammalian arenaviruses can cross the species barrier from their natural rodent hosts to humans, resulting in illnesses ranging from mild flu-like syndromes to severe and fatal haemorrhagic zoonoses. The increased frequency of outbreaks and associated high fatality rates of the most prevalent arenavirus, Lassa, in West African countries, highlights the significant risk to public health and to the socio-economic development of affected countries. The devastating impact of these viruses is further exacerbated by the lack of approved vaccines and effective treatments. Differential immune responses to arenavirus infections that can lead to either clearance or rapid, widespread and uncontrolled viral dissemination are modulated by the arenavirus multifunctional proteins, NP and Z. These two proteins control the antiviral response to infection by targeting multiple cellular pathways; and thus, represent attractive targets for antiviral development to counteract infection. The interplay between the host immune responses and viral replication is a key determinant of virus pathogenicity and disease outcome. In this review, we examine the current understanding of host immune defenses against arenavirus infections and summarise the host protein interactions of NP and Z and the mechanisms that govern immune evasion strategies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412275/ doi: 10.3390/v12070784 id: cord-266901-oyevbxtc author: Su, Airong title: Opposite Roles of RNase and Kinase Activities of Inositol-Requiring Enzyme 1 (IRE1) on HSV-1 Replication date: 2017-08-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In response to the endoplasmic reticulum (ER) stress induced by herpes simplex virus type 1 (HSV-1) infection, host cells activate the unfolded protein response (UPR) to reduce the protein-folding burden in the ER. The regulation of UPR upon HSV-1 infection is complex, and the downstream effectors can be detrimental to viral replication. Therefore, HSV-1 copes with the UPR to create a beneficial environment for its replication. UPR has three branches, including protein kinase RNA (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activated transcription factor 6 (ATF6). IRE1α is the most conserved branch of UPR which has both RNase and kinase activities. Previous studies have shown that IRE1α RNase activity was inactivated during HSV-1 infection. However, the effect of the two activities of IRE1α on HSV-1 replication remains unknown. Results in this study showed that IRE1α expression was up-regulated during HSV-1 infection. We found that in HEC-1-A cells, increasing RNase activity, or inhibiting kinase activity of IRE1α led to viral suppression, indicating that the kinase activity of IRE1α was beneficial, while the RNase activity was detrimental to viral replication. Further evidence showed that the kinase activity of IRE1α leads to the activation of the JNK (c-Jun N-terminal kinases) pathway, which enhances viral replication. Taken together, our evidence suggests that IRE1α is involved in HSV-1 replication, and its RNase and kinase activities play differential roles during viral infection. url: https://www.ncbi.nlm.nih.gov/pubmed/28832521/ doi: 10.3390/v9090235 id: cord-009399-6zpkpdzu author: Sun, Fang title: Topology, Antiviral Functional Residues and Mechanism of IFITM1 date: 2020-03-08 words: 5697.0 sentences: 354.0 pages: flesch: 57.0 cache: ./cache/cord-009399-6zpkpdzu.txt txt: ./txt/cord-009399-6zpkpdzu.txt summary: Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Some studies suggest that IFITM proteins may suppress the entry of viruses by inhibiting the hemifusion of viral membrane and host cell membranes [15] or restricting the formation of fusion pores following virus-endosome hemifusion [16] . Alanine scanning and site-directed mutations found that KRRK basic residues were key for the restriction of IFITM proteins on ZIKV and DENV. Significantly, we found that IFITM1 can restrict the release of ZIKV from endosome to cytosol to prevent the entry of viral particles into host cells, which was associated with its inhibition on organelles acidification. abstract: Interferon-inducible transmembrane proteins (IFITM1/2/3) have been reported to suppress the entry of a wide range of viruses. However, their antiviral functional residues and specific mechanisms are still unclear. Here, we firstly resolved the topology of IFITM1 on the plasma membrane where N-terminus points into the cytoplasm and C-terminus resides extracellularly. Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Similarly, KRRK basic residues of IFITM2/3 also contributed to suppressing ZIKV replication. Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Overall, our study provided topology, antiviral functional residues and the mechanism of interferon-inducible transmembrane proteins. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150853/ doi: 10.3390/v12030295 id: cord-260431-eksl7pp8 author: Sun, Heting title: Isolation and Identification of Feline Herpesvirus Type 1 from a South China Tiger in China date: 2014-02-28 words: 2523.0 sentences: 140.0 pages: flesch: 55.0 cache: ./cache/cord-260431-eksl7pp8.txt txt: ./txt/cord-260431-eksl7pp8.txt summary: In the present study, we used molecular methods, virus isolation, TEM examination and an animal challenge experiment to diagnose the cause of death of the South China tiger, and for the first time, we confirmed the infection with FHV-1 in the captive tiger population in China. The phylogenetic tree based on the TK gene sequences showed that the isolate investigated in this study, was closely related to the ten isolates of FHV-1 ( Figure 2 ), a result consistent with the alignment analysis. By PCR/RT-PCR, the only virus detected in the trachea homogenates was FHV-1, which was confirmed afterwards by virus isolation, the TEM examination of cell cultures showing CPE, and a challenge experiment in cats. In this study, the authors described the first occurrence of feline herpesvirus type 1 (FHV-1) in a South China tiger in China. abstract: In 2012, an FHV-1-like virus was isolated from a tiger that presented with clinical signs of sialorrhea, sneezing and purulent rhinorrhea. Isolation was performed with the FK81 cell line, and the virus was identified by PCR, transmission electron microscopy (TEM), and the phylogenetic analysis of the partial thymidine kinase (TK) and glycoprotein B (gB) genes. A total of 253 bp of the TK gene and 566 bp of the gB gene were amplified from the trachea of the tiger by PCR/RT-PCR method. Phylogenetic analysis showed that the isolate belonged to the same cluster with other FHV-1 strains obtained from GenBank. Herpes-like viruses with an envelope and diameters of approximately 200 nm were observed in the culture supernatants of FK81 cells inoculated with samples from the tiger. The FHV-1 infection was confirmed by an animal challenge experiment in a cat model. Our finding extends the host range of FHV-1 and has implications for FHV-1 infection and South China tiger conservation. url: https://www.ncbi.nlm.nih.gov/pubmed/24590411/ doi: 10.3390/v6031004 id: cord-258684-lq4knxgf author: Takano, Tomomi title: Antiviral Effects of Hydroxychloroquine and Type I Interferon on In Vitro Fatal Feline Coronavirus Infection date: 2020-05-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Feline infectious peritonitis (FIP) is a viral disease with a high morbidity and mortality by the FIP virus (FIPV, virulent feline coronavirus). Several antiviral drugs for FIP have been identified, but many of these are expensive and not available in veterinary medicine. Hydroxychloroquine (HCQ) is a drug approved by several countries to treat malaria and immune-mediated diseases in humans, and its antiviral effects on other viral infections (e.g., SARS-CoV-2, dengue virus) have been confirmed. We investigated whether HCQ in association with interferon-ω (IFN-ω) is effective for FIPV in vitro. A total of 100 μM of HCQ significantly inhibited the replication of types I and II FIPV. Interestingly, the combination of 100 μM of HCQ and 10(4) U/mL of recombinant feline IFN-ω (rfIFN-ω, veterinary registered drug) increased its antiviral activity against type I FIPV infection. Our study suggested that HCQ and rfIFN-ω are applicable for treatment of FIP. Further clinical studies are needed to verify the combination of HCQ and rIFN-ω will be effective and safe treatment for cats with FIP. url: https://doi.org/10.3390/v12050576 doi: 10.3390/v12050576 id: cord-297092-oq14cwka author: Tan, Shaoyuan title: Characterization of Emerging Swine Viral Diseases through Oxford Nanopore Sequencing Using Senecavirus A as a Model date: 2020-10-07 words: 6982.0 sentences: 332.0 pages: flesch: 53.0 cache: ./cache/cord-297092-oq14cwka.txt txt: ./txt/cord-297092-oq14cwka.txt summary: This study developed whole genome sequencing methods to facilitate the control of SVA and provide a reference for the timely detection and prevention of other emerging infectious diseases. For the sequencing of cell culture samples, raw pass reads were mapped to the SVA reference genome (GenBank: MN164664) using Minimap2 [34] , then analyzed using Qualimap [35] , generating raw error rates and coverage information which was then visualized using GraphPad prism software (GraphPad Software, San Diego, CA, USA). After determining the consensus generation strategies for both sequencing methods, optimization was performed in terms of total input sequencing yield and the pre-treatment of raw reads using the cell culture virus in which the whole genome sequence was already known. In order to evaluate and compare the general performance of DRS and PCS for viral whole genome recovery, two whole genome sequencing runs using a cell culture-grown virus with a known reference sequence were carried out for each method (Table 1 ). abstract: Emerging viral infectious diseases present a major threat to the global swine industry. Since 2015, Senecavirus A (SVA) has been identified as a cause of vesicular disease in different countries and is considered an emerging disease. Despite the growing concern about SVA, there is a lack of preventive and diagnostic strategies, which is also a problem for all emerging infectious diseases. Using SVA as a model, we demonstrated that Oxford Nanopore MinION sequencing could be used as a robust tool for the investigation and surveillance of emerging viral diseases. Our results identified that MinION sequencing allowed for rapid, unbiased pathogen detection at the species and strain level for clinical cases. SVA whole genome sequences were generated using both direct RNA sequencing and PCR-cDNA sequencing methods, with an optimized consensus accuracy of 94% and 99%, respectively. The advantages of direct RNA sequencing lie in its shorter turnaround time, higher analytical sensitivity and its quantitative relationship between input RNA and output sequencing reads, while PCR-cDNA sequencing excelled at creating highly accurate sequences. This study developed whole genome sequencing methods to facilitate the control of SVA and provide a reference for the timely detection and prevention of other emerging infectious diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/33036361/ doi: 10.3390/v12101136 id: cord-004509-jkzqmkz6 author: Thirion, Laurence title: Lyophilized Matrix Containing Ready-to-Use Primers and Probe Solution for Standardization of Real-Time PCR and RT-qPCR Diagnostics in Virology date: 2020-01-30 words: 4393.0 sentences: 194.0 pages: flesch: 47.0 cache: ./cache/cord-004509-jkzqmkz6.txt txt: ./txt/cord-004509-jkzqmkz6.txt summary: In conclusion, Lyoph-P&P holds several advantages over extemporaneously preparer liquid formulation that merit to be considered when a novel real-time molecular assay is implemented in a laboratory in charge of routine diagnostic activity. Selected assays target two emerging viruses that are listed on the blueprint of the WHO as to be considered for preparedness and response actions [5] : chikungunya virus (CHIKV), a single-stranded positive-sense RNA alphavirus, and Rift Valley fever phlebovirus (RVFV), a tri-segmented, single-stranded negative-sense RNA phlebovirus. Detection of CHIKV RNA using Lyoph-P&P provides results in clinical samples that are at least equal and often better than those obtained with the extemporaneously prepared liquid formulation used as reference. Indeed, at laboratory level, it is likely that one or two different formats (number of tests per vial) will be either prepared or ordered; as a consequence, the time during which rehydrated material can be stored without affecting the expected performances of the assay is a key factor. abstract: Real-time molecular techniques have become the reference methods for direct diagnosis of pathogens. The reduction of steps is a key factor in order to decrease the risk of human errors resulting in invalid series and delayed results. We describe here a process of preparation of oligonucleotide primers and hydrolysis probe in a single tube at predefined optimized concentrations that are stabilized via lyophilization (Lyoph-P&P). Lyoph-P&P was compared versus the classic protocol using extemporaneously prepared liquid reagents using (i) sensitivity study, (ii) long-term stability at 4 °C, and (iii) long-term stability at 37 °C mimicking transportation without cold chain. Two previously published molecular assays were selected for this study. They target two emerging viruses that are listed on the blueprint of the WHO as to be considered for preparedness and response actions: chikungunya virus (CHIKV) and Rift Valley fever phlebovirus (RVFV). Results of our study demonstrate that (i) Lyoph-P&P is stable for at least 4 days at 37 °C supporting shipping without the need of cold chain, (ii) Lyoph-P&P rehydrated solution is stable at +4 °C for at least two weeks, (iii) sensitivity observed with Lyoph-P&P is at least equal to, often better than, that observed with liquid formulation, (iv) validation of results observed with low-copy specimens is rendered easier by higher fluorescence level. In conclusion, Lyoph-P&P holds several advantages over extemporaneously preparer liquid formulation that merit to be considered when a novel real-time molecular assay is implemented in a laboratory in charge of routine diagnostic activity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077261/ doi: 10.3390/v12020159 id: cord-268788-jcu3pasy author: Thor, Sharmi W. title: Recombination in Avian Gamma-Coronavirus Infectious Bronchitis Virus date: 2011-09-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Recombination in the family Coronaviridae has been well documented and is thought to be a contributing factor in the emergence and evolution of different coronaviral genotypes as well as different species of coronavirus. However, there are limited data available on the frequency and extent of recombination in coronaviruses in nature and particularly for the avian gamma-coronaviruses where only recently the emergence of a turkey coronavirus has been attributed solely to recombination. In this study, the full-length genomes of eight avian gamma-coronavirus infectious bronchitis virus (IBV) isolates were sequenced and along with other full-length IBV genomes available from GenBank were analyzed for recombination. Evidence of recombination was found in every sequence analyzed and was distributed throughout the entire genome. Areas that have the highest occurrence of recombination are located in regions of the genome that code for nonstructural proteins 2, 3 and 16, and the structural spike glycoprotein. The extent of the recombination observed, suggests that this may be one of the principal mechanisms for generating genetic and antigenic diversity within IBV. These data indicate that reticulate evolutionary change due to recombination in IBV, likely plays a major role in the origin and adaptation of the virus leading to new genetic types and strains of the virus. url: https://doi.org/10.3390/v3091777 doi: 10.3390/v3091777 id: cord-351365-dc9t3vh3 author: Todt, Daniel title: Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations date: 2016-10-13 words: 6318.0 sentences: 320.0 pages: flesch: 40.0 cache: ./cache/cord-351365-dc9t3vh3.txt txt: ./txt/cord-351365-dc9t3vh3.txt summary: Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis. Figure 1 provides an overview of a selection of RNA viruses against which RBV was shown to be active: hepatitis C virus (HCV, Flaviviridae), dengue virus (DENV, Flaviviridae), respiratory syncytial virus (RSV, Paramyxoviridae), influenza A and B virus (Orthomyxoviridae), chikungunya virus (CHIKV, Togaviridae), poliovirus (Picornaviridae), Hantaan virus (Bunyaviridae), and Lassa virus (Arenaviridae) [28, 29] ( Figure 1 ). Furthermore, mechanisms on the virus itself were described by inhibition of the capping efficiency, the viral polymerase, and a mutagenic effect on newly synthesized RNA genomes. A Mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients abstract: Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/27754363/ doi: 10.3390/v8100283 id: cord-004507-ezuyjcxs author: Tomazatos, Alexandru title: Letea Virus: Comparative Genomics and Phylogenetic Analysis of a Novel Reassortant Orbivirus Discovered in Grass Snakes (Natrix natrix) date: 2020-02-21 words: 6326.0 sentences: 348.0 pages: flesch: 49.0 cache: ./cache/cord-004507-ezuyjcxs.txt txt: ./txt/cord-004507-ezuyjcxs.txt summary: The study provided complete genome sequences for nine Letea virus strains and new information about orbivirus diversity, host range, ecology and evolution. The phylogenetic clustering of Orbivirus members results in clades indicating their putative or potential arthropod vectors: Culicoidesor sand fly-borne (C/SBOV), mosquito-borne (MBOV) and tick-borne orbiviruses (TBOV) [9] . Evolutionary relationship of LEAV with representative members of the Orbivirus genus were analyzed by inferring phylogenetic trees with amino acid and nucleotide ORF sequences of conserved genes encoding the polymerase (VP1), the subcore shell protein T2 (VP2/VP3) and the major core surface protein T13 (VP7) [5, 6] . Inclusion and demarcation of species within the Orbivirus genus considers several criteria, such as sequence identity of segments encoding the polymerase (VP1) and major subcore shell protein T2, gene reassortment between close strains, high levels of serological cross-reactivity against conserved antigens like the T13 protein, conservation of UTR terminal nucleotides, range of hosts and vectors or the clinical signs associated with orbivirus infection [1] . abstract: The discovery and characterization of novel arthropod-borne viruses provide valuable information on their genetic diversity, ecology, evolution and potential to threaten animal or public health. Arbovirus surveillance is not conducted regularly in Romania, being particularly very scarce in the remote and diverse areas like the Danube Delta. Here we describe the detection and genetic characterization of a novel orbivirus (Reoviridae: Orbivirus) designated as Letea virus, which was found in grass snakes (Natrix natrix) during a metagenomic and metatranscriptomic survey conducted between 2014 and 2017. This virus is the first orbivirus discovered in reptiles. Phylogenetic analyses placed Letea virus as a highly divergent species in the Culicoides-/sand fly-borne orbivirus clade. Gene reassortment and intragenic recombination were detected in the majority of the nine Letea virus strains obtained, implying that these mechanisms play important roles in the evolution and diversification of the virus. However, the screening of arthropods, including Culicoides biting midges collected within the same surveillance program, tested negative for Letea virus infection and could not confirm the arthropod vector of the virus. The study provided complete genome sequences for nine Letea virus strains and new information about orbivirus diversity, host range, ecology and evolution. The phylogenetic associations warrant further screening of arthropods, as well as sustained surveillance efforts for elucidation of Letea virus natural cycle and possible implications for animal and human health. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077223/ doi: 10.3390/v12020243 id: cord-338436-0z828org author: Tzou, Philip L. title: Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds date: 2020-09-09 words: 8193.0 sentences: 522.0 pages: flesch: 46.0 cache: ./cache/cord-338436-0z828org.txt txt: ./txt/cord-338436-0z828org.txt summary: Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. Figure 4 displays EC 50 values for many of the directly acting antiviral compounds currently in clinical trials for the treatment of COVID-19 including six polymerase inhibitors (remdesivir, EIDD-2801, favipiravir, ribavirin, galidesivir, and sofosbuvir), three HIV-1 protease inhibitors (lopinavir, atazanavir, and darunavir), and three entry inhibitors (receptor binding monoclonal antibodies, soluble recombinant human ACE2, and umifenovir). Viruses 2020, 12, x FOR PEER REVIEW 11 of 22 Table 4 describes a set of the most promising compounds for the treatment of SARS-CoV-2 based on the following criteria: (i) act by a validated direct or indirect antiviral mechanism, (ii) display submicromolar activity in vitro and/or inhibitory activity in an animal model, and (iii) have a record of safety and favorable pharmacokinetics in human subjects. abstract: Background: To prioritize the development of antiviral compounds, it is necessary to compare their relative preclinical activity and clinical efficacy. Methods: We reviewed in vitro, animal model, and clinical studies of candidate anti-coronavirus compounds and placed extracted data in an online relational database. Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for 85% of the data. Approximately 75% of experiments involved compounds with known or likely mechanisms of action, including monoclonal antibodies and receptor binding inhibitors (21%), viral protease inhibitors (17%), miscellaneous host-acting inhibitors (10%), polymerase inhibitors (9%), interferons (7%), fusion inhibitors (5%), and host protease inhibitors (5%). Of 975 compounds with known or likely mechanism, 135 (14%) are licensed in the U.S. for other indications, 197 (20%) are licensed outside the U.S. or are in human trials, and 595 (61%) are pre-clinical investigational compounds. Conclusion: CoV-RDB facilitates comparisons between different candidate antiviral compounds, thereby helping scientists, clinical investigators, public health officials, and funding agencies prioritize the most promising compounds and repurposed drugs for further development. url: https://www.ncbi.nlm.nih.gov/pubmed/32916958/ doi: 10.3390/v12091006 id: cord-252142-aqwlcs9g author: Uematsu, Jun title: Legume Lectins Inhibit Human Parainfluenza Virus Type 2 Infection by Interfering with the Entr date: 2012-06-29 words: 3037.0 sentences: 167.0 pages: flesch: 55.0 cache: ./cache/cord-252142-aqwlcs9g.txt txt: ./txt/cord-252142-aqwlcs9g.txt summary: Three lectins with different sugar binding specificities were investigated for anti-viral activity against human parainfluenza virus type 2 (hPIV-2). The lectins, concanavalin A (Con A), lens culinaris agglutinin (LCA) and peanut agglutinin (PNA), inhibited cell fusion and hemadsorption induced by hPIV-2. Using a recombinant green fluorescence protein-expressing hPIV-2, without matrix protein (rghPIV-2ΔM), it was found that virus entry into the cells was not completely prevented. The inhibitory effect of lectins on hPIV-2 entry into the cells and replication in the cells was analyzed using a recombinant green fluorescence protein-expressing hPIV-2 without matrix (M) protein (rghPIV-2ΔM) [9] . RNA was prepared from the lectin-treated infected cells at four days post infection, and virus-synthesized RNA was analyzed using hPIV-2 specific primers by polymerase chain reaction (PCR). These results indicated that the lectins bound to the cell surface receptors, and largely prevented the binding of hPIV-2 to the cells non-specifically. abstract: Three lectins with different sugar binding specificities were investigated for anti-viral activity against human parainfluenza virus type 2 (hPIV-2). The lectins, concanavalin A (Con A), lens culinaris agglutinin (LCA) and peanut agglutinin (PNA), inhibited cell fusion and hemadsorption induced by hPIV-2. Virus nucleoprotein (NP) gene synthesis was largely inhibited, but fusion (F) and hemagglutinin-neuraminidase (HN) gene syntheses were not. An indirect immunofluorescence study showed that Con A inhibited virus NP, F and HN protein syntheses, but LCA did not completely inhibit them, and that PNA inhibited only NP protein synthesis. Using a recombinant green fluorescence protein-expressing hPIV-2, without matrix protein (rghPIV-2ΔM), it was found that virus entry into the cells was not completely prevented. The lectins considerably reduced the number of viruses released compared with that of virus infected cells. The lectins bound to cell surface within 10 min, and many aggregates were observed at 30 min. Con A and LCA slightly disrupted actin microfilaments and microtubules, but PNA had almost no effect on them. These results indicated that the inhibitory effects of the lectins were caused mainly by the considerable prevention of virus adsorption to the cells by the lectin binding to their receptors. url: https://www.ncbi.nlm.nih.gov/pubmed/22852043/ doi: 10.3390/v4071104 id: cord-280782-8gbktpt3 author: Van Brussel, Kate title: Distinct Lineages of Feline Parvovirus Associated with Epizootic Outbreaks in Australia, New Zealand and the United Arab Emirates date: 2019-12-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Feline panleukopenia (FPL), a frequently fatal disease of cats, is caused by feline parvovirus (FPV) or canine parvovirus (CPV). We investigated simultaneous outbreaks of FPL between 2014 and 2018 in Australia, New Zealand and the United Arab Emirates (UAE) where FPL outbreaks had not been reported for several decades. Case data from 989 cats and clinical samples from additional 113 cats were obtained to determine the cause of the outbreaks and epidemiological factors involved. Most cats with FPL were shelter-housed, 9 to 10 weeks old at diagnosis, unvaccinated, had not completed a primary vaccination series or had received vaccinations noncompliant with current guidelines. Analysis of parvoviral VP2 sequence data confirmed that all FPL cases were caused by FPV and not CPV. Phylogenetic analysis revealed that each of these outbreaks was caused by a distinct FPV, with two virus lineages present in eastern Australia and virus movement between different geographical locations. Viruses from the UAE outbreak formed a lineage of unknown origin. FPV vaccine virus was detected in the New Zealand cases, highlighting the difficulty of distinguishing the co-incidental shedding of vaccine virus in vaccinated cats. Inadequate vaccination coverage in shelter-housed cats was a common factor in all outbreaks, likely precipitating the multiple re-emergence of infection events. url: https://doi.org/10.3390/v11121155 doi: 10.3390/v11121155 id: cord-350964-0jtfc271 author: Van Nguyen, Dung title: Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam date: 2018-02-28 words: 4803.0 sentences: 246.0 pages: flesch: 51.0 cache: ./cache/cord-350964-0jtfc271.txt txt: ./txt/cord-350964-0jtfc271.txt summary: In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Nucleic acid that was extracted from liver samples of 157 bats (29 species; Table S1 ) and 470 rodents (six species) was screened for pegivirus and human hepatitis B, C, E viruses and their homologues ( Table 1 ) by nested and semi-nested PCR assays with degenerate primers. abstract: Rodents and bats are now widely recognised as important sources of zoonotic virus infections in other mammals, including humans. Numerous surveys have expanded our knowledge of diverse viruses in a range of rodent and bat species, including their origins, evolution, and range of hosts. In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Complete or near-complete genome sequences of HBV, HEV and pegivirus homologues closely resembled those previously reported from rodents and bats. However, complete coding region sequences of the rodent hepacivirus-like viruses substantially diverged from all of the currently classified variants and potentially represent a new species in the Hepacivirus genus. Of the viruses identified, their routes of transmission and potential to establish zoonoses remain to be determined. url: https://doi.org/10.3390/v10030102 doi: 10.3390/v10030102 id: cord-272391-0imlae98 author: Van der Gucht, Winke title: Isolation and Characterization of Clinical RSV Isolates in Belgium during the Winters of 2016–2018 date: 2019-11-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Respiratory Syncytial Virus (RSV) is a very important viral pathogen in children, immunocompromised and cardiopulmonary diseased patients and the elderly. Most of the published research with RSV was performed on RSV Long and RSV A2, isolated in 1956 and 1961, yet recent RSV isolates differ from these prototype strains. Additionally, these viruses have been serially passaged in cell culture, which may result in adaptations that affect virus–host interactions. We have isolated RSV from mucosal secretions of 12 patients in the winters 2016–2017 and 2017–2018, of which eight RSV-A subtypes and four RSV-B subtypes. Passage 3 of the isolates was assessed for viral replication kinetics and infectious virus production in HEp-2, A549 and BEAS-2B cells, thermal stability at 37 °C, 32 °C and 4 °C, syncytia formation, neutralization by palivizumab and mucin mRNA expression in infected A549 cells. We observed that viruses isolated in one RSV season show differences on the tested assays. Furthermore, comparison with RSV A2 and RSV B1 reveals for some RSV isolates differences in viral replication kinetics, thermal stability and fusion capacity. Major differences are, however, not observed and differences between the recent isolates and reference strains is, overall, similar to the observed variation in between the recent isolates. One clinical isolate (BE/ANT-A11/17) replicated very efficiently in all cell lines, and remarkably, even better than RSV A2 in the HEp-2 cell line. url: https://www.ncbi.nlm.nih.gov/pubmed/31698728/ doi: 10.3390/v11111031 id: cord-353609-no3mbg5d author: Vandegrift, Kurt J. title: An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses date: 2011-04-15 words: 6925.0 sentences: 350.0 pages: flesch: 42.0 cache: ./cache/cord-353609-no3mbg5d.txt txt: ./txt/cord-353609-no3mbg5d.txt summary: Conducting viral surveillance in animal reservoirs and invertebrate vectors can help explain circulation within host species; observed patterns of zoonotic transmission; and even allow for the prediction of periods of increased risk of zoonotic transmission (e.g., Rift valley fever and rainfall [25] ; West Nile virus (WNV) and American robin (Turdus turdus) migration [26] ; as well as hantavirus in mice [27, 28] ). Globalization, host ecology, host-virus dynamics, climate change, and anthropogenic landscape changes all contribute to the complexity of zoonotic viral emergence and disease, and create significant conservation and public health challenges. While the lasting efficacy of wildlife vaccination efforts has yet to be demonstrated with either endangered species or in breaking the transmission cycle of human pathogens, an increasing number of researchers are drawing attention to systems where it seems feasible [99, 103] ; demonstrating that intricate knowledge of host and virus ecology can greatly reduce the amount of vaccine coverage that is necessary to control these viruses. abstract: The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today’s globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues. url: https://doi.org/10.3390/v3040379 doi: 10.3390/v3040379 id: cord-307046-ko3bdvo0 author: Vasilakis, Nikos title: Exploiting the Legacy of the Arbovirus Hunters date: 2019-05-23 words: 17749.0 sentences: 879.0 pages: flesch: 44.0 cache: ./cache/cord-307046-ko3bdvo0.txt txt: ./txt/cord-307046-ko3bdvo0.txt summary: Complete genome sequences are now available for many of the archived isolates, allowing more accurate taxonomic assignments, analysis of their phylogenetic and evolutionary relationships with other viruses, and evaluation of the potential risks they may present to humans and wild or domestic animal populations. Scientists in these field laboratories were involved in the detection and investigation of human diseases in their respective geographic regions, surveying human and animal populations for serologic evidence of past viral infection, and searching for viruses in a wide variety of arthropods, mammals, birds, reptiles, and amphibians [2] . The family contains several serious human pathogens, including dengue, yellow fever, Zika, Japanese encephalitis, West Nile, and tick-borne encephalitis viruses (all arboviruses in the genus Flavivirus) and the hepatitis C virus (a member of the genus Hepacivirus). abstract: In recent years, it has become evident that a generational gap has developed in the community of arbovirus research. This apparent gap is due to the dis-investment of training for the next generation of arbovirologists, which threatens to derail the rich history of virus discovery, field epidemiology, and understanding of the richness of diversity that surrounds us. On the other hand, new technologies have resulted in an explosion of virus discovery that is constantly redefining the virosphere and the evolutionary relationships between viruses. This paradox presents new challenges that may have immediate and disastrous consequences for public health when yet to be discovered arboviruses emerge. In this review we endeavor to bridge this gap by providing a historical context for the work being conducted today and provide continuity between the generations. To this end, we will provide a narrative of the thrill of scientific discovery and excitement and the challenges lying ahead. url: https://doi.org/10.3390/v11050471 doi: 10.3390/v11050471 id: cord-330767-jja2wcfz author: Voigt, Kathleen title: Fusogenicity of the Ghana Virus (Henipavirus: Ghanaian bat henipavirus) Fusion Protein is Controlled by the Cytoplasmic Domain of the Attachment Glycoprotein date: 2019-08-29 words: 6059.0 sentences: 263.0 pages: flesch: 48.0 cache: ./cache/cord-330767-jja2wcfz.txt txt: ./txt/cord-330767-jja2wcfz.txt summary: Here, we generated truncated as well as chimeric GhV G proteins and investigated the influence of the structural domains (cytoplasmic tail, transmembrane domain, ectodomain) of this protein on the intracellular transport and the fusogenicity following coexpression with the GhV fusion protein (F). In previous studies, it has been shown that the transport of GhV G to the cell surface is significantly reduced compared to NiV G and that the majority of the GhV G protein accumulates in the endoplasmic reticulum (ER), suggesting that the amount of surface-expressed GhV G is not efficient enough to trigger conformational changes in the F protein that are required to acquire the fusion-active form of F [35, 36] . However, whereas the glycoproteins of NiV and HeV induce cell-to-cell fusion in a broad variety of cells from different host species, syncytium formation upon expression of GhV F and G proteins is restricted to certain bat cells [32] [33] [34] [35] . abstract: The Ghana virus (GhV) is phylogenetically related to the zoonotic henipaviruses Nipah (NiV) and Hendra virus. Although GhV uses the highly conserved receptor ephrin-B2, the fusogenicity is restricted to cell lines of bat origin. Furthermore, the surface expression of the GhV attachment glycoprotein (G) is reduced compared to NiV and most of this protein is retained in the endoplasmic reticulum (ER). Here, we generated truncated as well as chimeric GhV G proteins and investigated the influence of the structural domains (cytoplasmic tail, transmembrane domain, ectodomain) of this protein on the intracellular transport and the fusogenicity following coexpression with the GhV fusion protein (F). We demonstrate that neither the cytoplasmic tail nor the transmembrane domain is responsible for the intracellular retention of GhV G. Furthermore, the cytoplasmic tail of GhV G modulates the fusogenicity of GhV F and therefore controls the species-restricted fusogenicity of the GhV surface glycoproteins. url: https://doi.org/10.3390/v11090800 doi: 10.3390/v11090800 id: cord-321080-pgxxkfc0 author: Wang, Cong title: Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD date: 2019-01-06 words: 4553.0 sentences: 191.0 pages: flesch: 49.0 cache: ./cache/cord-321080-pgxxkfc0.txt txt: ./txt/cord-321080-pgxxkfc0.txt summary: We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. As shown in Figure 2 and Table 1 , combining HR2P-M2 and m336 resulted in strong synergistic inhibitory activity against MERS-CoV pseudovirus infection with CI values of 0.13-0.20 for 50-90% inhibition, including potency enhancement of 12.9-to 18.9-fold for m336 and 8.4-to 12.9-fold for HR2P-M2. abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. Thus, this combinatorial strategy could be used in clinics for the urgent treatment of MERS-CoV-infected patients. url: https://www.ncbi.nlm.nih.gov/pubmed/30621343/ doi: 10.3390/v11010031 id: cord-345651-admlzeu4 author: Wang, Gang title: The N-Terminal Domain of Spike Protein Is Not the Enteric Tropism Determinant for Transmissible Gastroenteritis Virus in Piglets date: 2019-03-30 words: 6220.0 sentences: 265.0 pages: flesch: 49.0 cache: ./cache/cord-345651-admlzeu4.txt txt: ./txt/cord-345651-admlzeu4.txt summary: Using a novel approach, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems efficiently and rapidly rescued another recombinant virus with a 224-amino-acid deletion in the N-terminal domain of the TGEV Spike gene (S_NTD224), which is analogous to the N-terminal domain of porcine respiratory coronavirus. Homologous recombination was then performed using the ClonExpress II One Step Cloning Kit (Vazyme, Nanjing, Jiangsu, China) according to the manufacturer''s instructions using 200 ng of recycled linearized pTGEV-GFP BAC, 45 ng of PCR products of S_NTD and two pairs of primers (rec-672SF/δS-NTDR and rec-672SR/δS-NTDF) ( Table 2) . To construct an infectious clone of TGEV, six overlapping cDNA fragments designated A to F were generated by reverse transcriptase PCR (RT-PCR) using total RNA extracted from PK-15 cells infected with TGEV WH-1 ( Figure 1A ,B). Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus abstract: Transmissible gastroenteritis virus (TGEV) is the etiologic agent of transmissible gastroenteritis in pigs, and the N-terminal domain of TGEV spike protein is generally recognized as both the virulence determinant and enteric tropism determinant. Here, we assembled a full-length infectious cDNA clone of TGEV in a bacterial artificial chromosome. Using a novel approach, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems efficiently and rapidly rescued another recombinant virus with a 224-amino-acid deletion in the N-terminal domain of the TGEV Spike gene (S_NTD224), which is analogous to the N-terminal domain of porcine respiratory coronavirus. S_NTD224 notably affected the TGEV growth kinetics in PK-15 cells but was not essential for recombinant virus survival. In animal experiments with 13 two-day-old piglets, the TGEV recombinant viruses with/without S_NTD224 deletion induced obvious clinical signs and mortality. Together, our results directly demonstrated that S_NTD224 of TGEV mildly influenced TGEV virulence but was not the enteric tropism determinant and provide new insights for the development of a new attenuated vaccine against TGEV. Importantly, the optimized reverse genetics platform used in this study will simplify the construction of mutant infectious clones and help accelerate progress in coronavirus research. url: https://www.ncbi.nlm.nih.gov/pubmed/30935078/ doi: 10.3390/v11040313 id: cord-259916-gr6v098c author: Wang, Hongliang title: Mechanisms of Cellular Membrane Reorganization to Support Hepatitis C Virus Replication date: 2016-05-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Like all positive-sense RNA viruses, hepatitis C virus (HCV) induces host membrane alterations for its replication termed the membranous web (MW). Assembling replication factors at a membranous structure might facilitate the processes necessary for genome replication and packaging and shield viral components from host innate immune defenses. The biogenesis of the HCV MW is a complex process involving a concerted effort of HCV nonstructural proteins with a growing list of host factors. Although a comprehensive understanding of MW formation is still missing, a number of important viral and host determinants have been identified. This review will summarize the recent studies that have led to our current knowledge of the role of viral and host factors in the biogenesis of the MWs and discuss how HCV uses this specialized membrane structure for its replication. url: https://doi.org/10.3390/v8050142 doi: 10.3390/v8050142 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: nan sentences: nan pages: flesch: nan cache: txt: summary: 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-001972-1zisomq5 author: Wang, Xue title: Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells date: 2016-02-02 words: 3921.0 sentences: 197.0 pages: flesch: 46.0 cache: ./cache/cord-001972-1zisomq5.txt txt: ./txt/cord-001972-1zisomq5.txt summary: These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways. Cells treated with pH1N1 had higher level of NF-kB phosphorylation and increased protein expression of NFAT and AP-1 ( Figure 3B ) relative to HIV-1 infection alone, suggesting pH1N1 infection can activate host transcription factors required for HIV-1 replication in Jurkat cells. These data indicate that pandemic influenza A (H1N1) infection can increase accumulation of CD4 protein and induce T cell signaling and activate host transcription factors required for HIV-1 replication. In conclusion, our results demonstrate that pandemic influenza A (H1N1) virus infection can induce cell death through apoptotic signaling pathways and promote HIV-1 replication through the MAPK and TCR-related signaling pathways in HIV-1-infected Jurkat cells. Pandemic influenza A (H1N1) virus infection is also able to reactivate HIV-1 replication from its state of latent infection through activating apoptosis and TCR-signaling pathways. abstract: Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776188/ doi: 10.3390/v8020033 id: cord-351228-hpo8bboi author: Wasilenko, Shawn T. title: Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis? date: 2013-01-24 words: 4260.0 sentences: 210.0 pages: flesch: 36.0 cache: ./cache/cord-351228-hpo8bboi.txt txt: ./txt/cord-351228-hpo8bboi.txt summary: Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. Nevertheless, a major conclusion of most series documenting outcomes in patients with PBC following liver transplantation is that CsA is associated with a lower incidence of recurrent disease [10] [11] [12] [13] [14] [15] [16] 18] . Other agents, such as hepatitis C virus (HCV) rely on cyclophilin A interactions with viral components of the replication complex to produce RNA transcripts, a process also blocked by CsA [64] [65] [66] [67] [68] [69] [70] [71] . Cyclosporine A protects against primary biliary cirrhosis recurrence after liver transplantation Long-term follow-up after recurrence of primary biliary cirrhosis after liver transplantation in 100 patients De novo autoimmune hepatitis following liver transplantation for primary biliary cirrhosis abstract: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are poorly understood autoimmune liver diseases. Immunosuppression is used to treat AIH and ursodeoxycholic acid is used to slow the progression of PBC. Nevertheless, a proportion of patients with both disorders progress to liver failure. Following liver transplantation, up to a third of patients with PBC experience recurrent disease. Moreover a syndrome referred to as “de novo AIH” occurs in a proportion of patients regardless of maintenance immunosuppression, who have been transplanted for disorders unrelated to AIH. Of note, the use of cyclosporine A appears to protect against the development of recurrent PBC and de novo AIH even though it is a less potent immunosuppressive compared to tacrolimus. The reason why cyclosporine A is protective has not been determined. However, a virus resembling mouse mammary tumor virus (MMTV) has been characterized in patients with PBC and AIH. Accordingly, we hypothesized that the protective effect of cyclosporine A in liver transplant recipients may be mediated by the antiviral activity of this cyclophilin inhibitor. Treatment of the MMTV producing MM5MT cells with different antivirals and immunosuppressive agents showed that both cyclosporine A and the analogue NIM811 inhibited MMTV production from the producer cells. Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. We also review the mechanisms of how both cyclosporine A and NIM811 may inhibit betaretrovirus production in vitro. url: https://doi.org/10.3390/v5020423 doi: 10.3390/v5020423 id: cord-256713-tlluxd11 author: Welch, David title: Is Network Clustering Detectable in Transmission Trees? date: 2011-06-03 words: 5841.0 sentences: 306.0 pages: flesch: 57.0 cache: ./cache/cord-256713-tlluxd11.txt txt: ./txt/cord-256713-tlluxd11.txt summary: [15] show that for a class of networks known as random intersection graphs in which individuals belong to one or more overlapping groups and groups form fully connected cliques, an increase in clustering reduces the epidemic threshold, that is, major outbreaks may occur at lower levels of transmissibility in highly clustered networks. They demonstrate that a rewiring of random intersection graphs that preserves the degree sequence but decreases clustering produces networks with similarly lowered epidemic thresholds and even smaller mean outbreak sizes. From a statistical point of view, these results indicate that even with full data from a particular epidemic outbreak, such as complete knowledge of the transmission tree, it is unlikely that the level of clustering in the underlying contact network could be accurately inferred independently of the degree distribution. abstract: Networks are often used to model the contact processes that allow pathogens to spread between hosts but it remains unclear which models best describe these networks. One question is whether clustering in networks, roughly defined as the propensity for triangles to form, affects the dynamics of disease spread. We perform a simulation study to see if there is a signal in epidemic transmission trees of clustering. We simulate susceptible-exposed-infectious-removed (SEIR) epidemics (with no re-infection) over networks with fixed degree sequences but different levels of clustering and compare trees from networks with the same degree sequence and different clustering levels. We find that the variation of such trees simulated on networks with different levels of clustering is barely greater than those simulated on networks with the same level of clustering, suggesting that clustering can not be detected in transmission data when re-infection does not occur. url: https://www.ncbi.nlm.nih.gov/pubmed/21731813/ doi: 10.3390/v3060659 id: cord-306004-amv0los1 author: Widagdo, W. title: Host Determinants of MERS-CoV Transmission and Pathogenesis date: 2019-03-19 words: 4525.0 sentences: 242.0 pages: flesch: 46.0 cache: ./cache/cord-306004-amv0los1.txt txt: ./txt/cord-306004-amv0los1.txt summary: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. MERS-CoV infection in these animals merely causes mild upper respiratory tract infection [17, 18] , but seroepidemiological studies showed that this virus has been circulating in dromedary camels for decades, suggesting the efficient transmission of MERS-CoV in this species [19] [20] [21] [22] . Given the fact that experimental in vivo infection studies and DPP4 expression analysis in different animal species revealed that dromedary camels are not the only animals in which MERS-CoV has an upper respiratory tract tropism [17, 18, 83, 84] , it is then relevant to question whether other animals can potentially spread MERS-CoV as well. abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. In dromedary camels, the virus only causes a mild infection but it spreads efficiently between animals. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. One of these host factors, the MERS-CoV receptor dipeptidyl peptidase-4 (DPP4), may be a critical determinant because it is variably expressed in MERS-CoV-susceptible species as well as in humans. This could partially explain inter- and intraspecies differences in the tropism, pathogenesis, and transmissibility of MERS-CoV. In this review, we explore the role of DPP4 and other host factors in MERS-CoV transmission and pathogenesis—such as sialic acids, host proteases, and interferons. Further characterization of these host determinants may potentially offer novel insights to develop intervention strategies to tackle ongoing outbreaks. url: https://www.ncbi.nlm.nih.gov/pubmed/30893947/ doi: 10.3390/v11030280 id: cord-320921-eumuid3r author: Widagdo, W. title: Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits date: 2019-04-24 words: 4829.0 sentences: 239.0 pages: flesch: 51.0 cache: ./cache/cord-320921-eumuid3r.txt txt: ./txt/cord-320921-eumuid3r.txt summary: Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission. Besides dromedary camels, other animal species, i.e. llamas, alpacas, and pigs have been shown to be susceptible and develop upper respiratory tract infection upon experimental intranasal MERS-CoV inoculation [9] [10] [11] . We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ). We found that rabbits inoculated with the MERS-CoV EMC strain and those with the Qatar15 strain developed an equally mild infection and shed similar levels of viral RNA in their nasal and throat swabs (Figure 3 ). abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission. url: https://www.ncbi.nlm.nih.gov/pubmed/31022948/ doi: 10.3390/v11040381 id: cord-004337-jtaz1gdp author: Wu, Fangfang title: A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses date: 2020-01-03 words: 5721.0 sentences: 283.0 pages: flesch: 53.0 cache: ./cache/cord-004337-jtaz1gdp.txt txt: ./txt/cord-004337-jtaz1gdp.txt summary: title: A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses Here, we report that production of SUDV VLPs has been accomplished in insect cells by the co-infection with recombinant baculoviruses rBV-GP-GP and rBV-VP40-VP40, and evaluate the ability of SUDV-VLPs to induce SUDV-specific humoral and cellular immune responses in vaccinated mice. To detect a SUDV-VLP-induced humoral immune response in vaccinated BALB/c mice, indirect ELISA and virus neutralization assay were performed to evaluate the production of SUDV GP-specific antibodies and neutralizing antibodies. Analysis of SUDV-VLP-induced specific IgG antibody response by indirect ELISA at two weeks after every immunization of vaccinated mice (C). Moreover, our study revealed that the B cells of mice of the group vaccinated with SUDV VLPs mixed with an ISA 201 adjuvant were activated at one week after the primary immunization (Figure 7 ). abstract: Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates; and human fatality rates are as high as 67%–90%. Since the Ebola virus was discovered in 1976, the only available treatments have been medical support or the emergency administration of experimental drugs. The absence of licensed vaccines and drugs against the Ebola virus impedes the prevention of viral infection. In this study, we generated recombinant baculoviruses (rBV) expressing the Sudan virus (SUDV) matrix structural protein (VP40) (rBV-VP40-VP40) or the SUDV glycoprotein (GP) (rBV-GP-GP), and SUDV virus-like particles (VLPs) were produced by co-infection of Sf9 cells with rBV-SUDV-VP40 and rBV-SUDV-GP. The expression of SUDV VP40 and GP in SUDV VLPs was demonstrated by IFA and Western blot analysis. Electron microscopy results demonstrated that SUDV VLPs had a filamentous morphology. The immunogenicity of SUDV VLPs produced in insect cells was evaluated by the immunization of mice. The analysis of antibody responses showed that mice vaccinated with SUDV VLPs and the adjuvant Montanide ISA 201 produced SUDV GP-specific IgG antibodies. Sera from SUDV VLP-immunized mice were able to block infection by SUDV GP pseudotyped HIV, indicating that a neutralizing antibody against the SUDV GP protein was produced. Furthermore, the activation of B cells in the group immunized with VLPs mixed with Montanide ISA 201 was significant one week after the primary immunization. Vaccination with the SUDV VLPs markedly increased the frequency of antigen-specific cells secreting type 1 and type 2 cytokines. To study the therapeutic effects of SUDV antibodies, horses were immunized with SUDV VLPs emulsified in Freund’s complete adjuvant or Freund’s incomplete adjuvant. The results showed that horses could produce SUDV GP-specific antibodies and neutralizing antibodies. These results showed that SUDV VLPs demonstrate excellent immunogenicity and represent a promising approach for vaccine development against SUDV infection. Further, these horse anti-SUDV purified immunoglobulins lay a foundation for SUDV therapeutic drug research. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019897/ doi: 10.3390/v12010064 id: cord-309635-1tgovkr7 author: Wu, Nicholas C. title: Structural Biology of Influenza Hemagglutinin: An Amaranthine Adventure date: 2020-09-22 words: 5497.0 sentences: 289.0 pages: flesch: 42.0 cache: ./cache/cord-309635-1tgovkr7.txt txt: ./txt/cord-309635-1tgovkr7.txt summary: Hemagglutinin (HA) glycoprotein is an important focus of influenza research due to its role in antigenic drift and shift, as well as its receptor binding and membrane fusion functions, which are indispensable for viral entry. Similarly, RBS of influenza B HA is composed of the 140-loop, 190-helix, and 240-loop, which are structurally equivalent to the 130-loop, 150-loop, and 190-helix Receptor specificity can also continue to evolve when seasonal viruses circulate in the human population, due to natural mutations that are likely a response to immune selection pressure. A broadly neutralizing human monoclonal antibody that recognizes a conserved, novel epitope on the globular head of the influenza H1N1 virus hemagglutinin Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin Design of nanoparticulate group 2 influenza virus hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages abstract: Hemagglutinin (HA) glycoprotein is an important focus of influenza research due to its role in antigenic drift and shift, as well as its receptor binding and membrane fusion functions, which are indispensable for viral entry. Over the past four decades, X-ray crystallography has greatly facilitated our understanding of HA receptor binding, membrane fusion, and antigenicity. The recent advances in cryo-EM have further deepened our comprehension of HA biology. Since influenza HA constantly evolves in natural circulating strains, there are always new questions to be answered. The incessant accumulation of knowledge on the structural biology of HA over several decades has also facilitated the design and development of novel therapeutics and vaccines. This review describes the current status of the field of HA structural biology, how we got here, and what the next steps might be. url: https://www.ncbi.nlm.nih.gov/pubmed/32971825/ doi: 10.3390/v12091053 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-352007-3djwbivp author: Xiang, Qi title: Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication date: 2020-07-14 words: 6873.0 sentences: 353.0 pages: flesch: 48.0 cache: ./cache/cord-352007-3djwbivp.txt txt: ./txt/cord-352007-3djwbivp.txt summary: Here, we primarily found that Beclin1 facilitates EV71 replication in human rhabdomyosarcoma (RD) cells and the autophagy was actually induced, but Beclin1 was not significantly affected at either mRNA level or protein level during early EV71 infection. The results show that the mRNA level and protein level of Beclin1 were significantly reduced in RD cells; moreover, knockdown of BECN1 inhibited EV71 replication ( Figure 3A,B) . Our group has previously reported several host factors regulating EV71 replication; for example, SIRT1 can inhibit EV71 replication and RNA translation by interfering with the viral polymerase and 5 UTR RNA [57] , and PolyC-Binding Protein 1 interacts with 5 -untranslated region of EV71 RNA in membrane-associated complex to facilitate viral replication [58] . In FMDV (Foot-and-mouth disease virus)-infected cells, the largest viral protein in the replication complex, 2C, would bind to Beclin1 to prevent the fusion of lysosomes to autophagosomes, allowing for virus survival [35] . abstract: Enterovirus 71 (EV71) is the main pathogen causing hand-foot-mouth disease (HFMD) in infants and children, which can also lead to severe neurological diseases and even death. Therefore, understanding the replication mechanism of EV71 is of great significance for the prevention and control of EV71-induced diseases. Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) is an important core protein for the initiation and the normal process of autophagy in cells. In addition to its involvement in autophagy, Beclin1 has also been reported to play an important role in cancer and innate immune signaling pathways. However, the role of Beclin1 in EV71 replication remains elusive. Here, we primarily found that Beclin1 facilitates EV71 replication in human rhabdomyosarcoma (RD) cells and the autophagy was actually induced, but Beclin1 was not significantly affected at either mRNA level or protein level during early EV71 infection. Further studies discovered that Beclin1 could interacts with EV71 non-structural protein 3D mainly through its evolutionary conserved domain (ECD) and coiled-coiled domain (CCD), thus promoting the replication of EV71 in human rhabdomyosarcoma (RD) cells and human astroglioma (U251) cells. Collectively, we reveal a novel regulatory mechanism associated with Beclin1 to promote EV71 replication, thus providing a potential therapeutic target for the prevention and control of EV71-associated diseases. url: https://doi.org/10.3390/v12070756 doi: 10.3390/v12070756 id: cord-339752-o6atz33c author: Xiao, Li title: ACE2: The Key Molecule for Understanding the Pathophysiology of Severe and Critical Conditions of COVID-19: Demon or Angel? date: 2020-04-28 words: 3937.0 sentences: 257.0 pages: flesch: 49.0 cache: ./cache/cord-339752-o6atz33c.txt txt: ./txt/cord-339752-o6atz33c.txt summary: According to a report based on 72,314 cases (test confirmed cases: 44,672 (62%) from the Chinese Center for Disease Control and Prevention, 81% of COVID-19 patients have cold-like symptoms and mild pneumonia, 14% have severe respiratory inflammation, and 5% have critical conditions including respiratory failure, septic shock, and/or multiple organ dysfunction or failure. Similar to SARS (severe acute respiratory syndrome, [2002] [2003] coronavirus (SARS-CoV) [3] , SARS-CoV-2 primarily uses the S protein to invade host cells through ACE2, an enzyme which is known to be important in the renin-angiotensin-aldosterone system (RAAS) [4, 5] . Since TMPRSS2 plays a very important role in SARS-CoV-2 cell entry and ACE2 dysfunction, blocking the activity of TMPRSS2 should be the primary strategy for preventing severe and critical conditions of COVID-19. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) abstract: Recently, the SARS-CoV-2 induced disease COVID-19 has spread all over the world. Nearly 20% of the patients have severe or critical conditions. SARS-CoV-2 exploits ACE2 for host cell entry. ACE2 plays an essential role in the renin–angiotensin–aldosterone system (RAAS), which regulates blood pressure and fluid balance. ACE2 also protects organs from inflammatory injuries and regulates intestinal functions. ACE2 can be shed by two proteases, ADAM17 and TMPRSS2. TMPRSS2-cleaved ACE2 allows SARS-CoV-2 cell entry, whereas ADAM17-cleaved ACE2 offers protection to organs. SARS-CoV-2 infection-caused ACE2 dysfunction worsens COVID-19 and could initiate multi-organ failure. Here, we will explain the role of ACE2 in the pathogenesis of severe and critical conditions of COVID-19 and discuss auspicious strategies for controlling the disease. url: https://doi.org/10.3390/v12050491 doi: 10.3390/v12050491 id: cord-338973-73a7uvyz author: Xu, Jiabao title: Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV date: 2020-02-22 words: 7110.0 sentences: 426.0 pages: flesch: 57.0 cache: ./cache/cord-338973-73a7uvyz.txt txt: ./txt/cord-338973-73a7uvyz.txt summary: After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The source of unexplained pneumonia was first discovered in Wuhan in Dec, 2019, and SARS-CoV-2, a new coronavirus, was isolated from the respiratory epithelium of patients. Hong Kong scholars found that, compared with ribavirin alone, patients treated with lopinavir/ritonavir and ribavirin had lower risk of acute respiratory distress syndrome (ARDS) or death caused by SARS-CoV [76, 77] . A high-resolution crystal structure of SARS-CoV-2 coronavirus 3CL hydrolase (Mpro) was announced after the outbreak of COVID-19 in the world [80] , and human coronaviruses (HCoVs) have been treated as severe pathogens in respiratory tract infections. abstract: After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/32098422/ doi: 10.3390/v12020244 id: cord-335614-qh98622y author: Xu, Puzhi title: A Multi-Omics Study of Chicken Infected by Nephropathogenic Infectious Bronchitis Virus date: 2019-11-16 words: 6543.0 sentences: 352.0 pages: flesch: 41.0 cache: ./cache/cord-335614-qh98622y.txt txt: ./txt/cord-335614-qh98622y.txt summary: These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout. The results of PCA and OPLA-DA analysis showed that there was an obvious separation between the content of the Con and Dis groups, revealing significant changes in the concentrations of metabolites in the kidney induced by NIBV infection. In addition, the transcriptomic analysis showed that NIBV infection also activated the RIG-I-like receptor signalling pathway (Figure 3f , signal 2), which included the transcriptional upregulation of genes such as MDA5, IPS-1, TRAF3, and IκB. In the present study, the ABCG2 mRNA was downregulated in the model group chicken kidneys, partially explaining the significantly increased uric acid levels caused by NIBV infection. abstract: Chicken gout resulting from nephropathogenic infectious bronchitis virus (NIBV) has become a serious kidney disease problem in chicken worldwide with alterations of the metabolic phenotypes in multiple metabolic pathways. To investigate the mechanisms in chicken responding to NIBV infection, we examined the global transcriptomic and metabolomic profiles of the chicken’s kidney using RNA-seq and GC–TOF/MS, respectively. Furthermore, we analyzed the alterations in cecal microorganism composition in chickens using 16S rRNA-seq. Integrated analysis of these three phenotypic datasets further managed to create correlations between the altered kidney transcriptomes and metabolome, and between kidney metabolome and gut microbiome. We found that 2868 genes and 160 metabolites were deferentially expressed or accumulated in the kidney during NIBV infection processes. These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. In addition, the comprehensive correlations between the kidney metabolome and cecal microbial community showed contributions of gut microbiota in the progression of NIBV-infection. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout. url: https://doi.org/10.3390/v11111070 doi: 10.3390/v11111070 id: cord-323569-ksodnkic author: Xu, Shengnan title: A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice date: 2019-12-11 words: 5550.0 sentences: 316.0 pages: flesch: 56.0 cache: ./cache/cord-323569-ksodnkic.txt txt: ./txt/cord-323569-ksodnkic.txt summary: title: A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. Immunization of mice with ISA 201VG mixed with Poly (I:C)-adjuvanted SBLP resulted in significant increases in SUDV GP-specific IgG, IgG1, and IgG2a and SUDV pseudotyped virus-neutralizing antibody titers, which are considered to be important correlates of protection [34, 49] . Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice abstract: Sudan virus (SUDV) causes severe lethal hemorrhagic fever in humans and nonhuman primates. The most effective and economical way to protect against Sudan ebolavirus disease is prophylactic vaccination. However, there are no licensed vaccines to prevent SUDV infections. In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. Expression of the recombinant GEM-displayed eGP (eGP-PA-GEM) was verified by Western blotting and immunofluorescence assays. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. The SBLP also elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. These data indicate that the SBLP subunit vaccine has the potential to be developed into a promising candidate vaccine against SUDV infections. url: https://doi.org/10.3390/v11121149 doi: 10.3390/v11121149 id: cord-259658-rgrt6e6r author: Yan, Bingpeng title: Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication date: 2019-01-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC–MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections. url: https://www.ncbi.nlm.nih.gov/pubmed/30654597/ doi: 10.3390/v11010073 id: cord-321441-t1v0pu0w author: Yang, Yiming title: Polycistronic Genome Segment Evolution and Gain and Loss of FAST Protein Function during Fusogenic Orthoreovirus Speciation date: 2020-06-29 words: 8639.0 sentences: 363.0 pages: flesch: 41.0 cache: ./cache/cord-321441-t1v0pu0w.txt txt: ./txt/cord-321441-t1v0pu0w.txt summary: New phylogenetic analyses that included the atypical waterfowl subgroup of avian reoviruses and recently identified new orthoreovirus species indicate a more complex relationship between reovirus speciation and fusogenic capacity, with numerous predicted internal indels and 5''-terminal extensions driving the evolution of the orthoreovirus'' polycistronic genome segments and their encoded FAST and fiber proteins. We further show that two distinct post-speciation genetic events led to the loss of fusion in the waterfowl isolates of avian reovirus, a recombination event that replaced the p10 FAST protein with a heterologous, non-fusogenic protein and point substitutions in a conserved motif that destroyed the p10 assembly into multimeric fusion platforms. MdRVs are divided into two subgroups, the "classical" and "novel" MdRVs. Classical Muscovy duck reoviruses (MdRVc) possess a bicistronic S4 genome segment encoding a truncated fiber protein of 269 residues and a p11 protein that lacks sequence similarity to the p10 FAST proteins of ARV, ARVN, and NBV ( Figure 1B ) [50] . abstract: The Reoviridae family is the only non-enveloped virus family with members that use syncytium formation to promote cell–cell virus transmission. Syncytiogenesis is mediated by a fusion-associated small transmembrane (FAST) protein, a novel family of viral membrane fusion proteins. Previous evidence suggested the fusogenic reoviruses arose from an ancestral non-fusogenic virus, with the preponderance of fusogenic species suggesting positive evolutionary pressure to acquire and maintain the fusion phenotype. New phylogenetic analyses that included the atypical waterfowl subgroup of avian reoviruses and recently identified new orthoreovirus species indicate a more complex relationship between reovirus speciation and fusogenic capacity, with numerous predicted internal indels and 5’-terminal extensions driving the evolution of the orthoreovirus’ polycistronic genome segments and their encoded FAST and fiber proteins. These inferred recombination events generated bi- and tricistronic genome segments with diverse gene constellations, they occurred pre- and post-orthoreovirus speciation, and they directly contributed to the evolution of the four extant orthoreovirus FAST proteins by driving both the gain and loss of fusion capability. We further show that two distinct post-speciation genetic events led to the loss of fusion in the waterfowl isolates of avian reovirus, a recombination event that replaced the p10 FAST protein with a heterologous, non-fusogenic protein and point substitutions in a conserved motif that destroyed the p10 assembly into multimeric fusion platforms. url: https://doi.org/10.3390/v12070702 doi: 10.3390/v12070702 id: cord-336536-ie5ok0lz author: Yeh, Ming Te title: Mapping Attenuation Determinants in Enterovirus-D68 date: 2020-08-08 words: 8258.0 sentences: 401.0 pages: flesch: 56.0 cache: ./cache/cord-336536-ie5ok0lz.txt txt: ./txt/cord-336536-ie5ok0lz.txt summary: A single amino acid change from isoleucine to valine at position 88 in VP3 attenuated neurovirulence by reducing virus replication in the brain and spinal cord of infected mice. To identify the potential virulence determinant, sequences of NR-49129, NR-49130, NR-49131 and CA/14-4231 were aligned to reveal conserved genetic changes that we defined as nucleotides in 5 -UTR and amino acids in the coding region that are present only in the non-pathogenic strain but not in pathogenic ones (Supplementary Data S1 and S2). While mutation VP1-L1P allowed a 50% survival of infected mice, VP3-I88V did not cause disease, suggesting its role as major virulence determinant for EV-D68 in this mouse model ( Figure 5E ). While mutation VP1-L1P allowed a 50% survival of infected mice, VP3-I88V did not cause disease, suggesting its role as major virulence determinant for EV-D68 in this mouse model ( Figure 5E ). abstract: Enterovirus (EV)-D68 has been associated with epidemics in the United Sates in 2014, 2016 and 2018. This study aims to identify potential viral virulence determinants. We found that neonatal type I interferon receptor knockout mice are susceptible to EV-D68 infection via intraperitoneal inoculation and were able to recapitulate the paralysis process observed in human disease. Among the EV-D68 strains tested, strain US/MO-14-18949 caused no observable disease in this mouse model, whereas the other strains caused paralysis and death. Sequence analysis revealed several conserved genetic changes among these virus strains: nucleotide positions 107 and 648 in the 5′-untranslated region (UTR); amino acid position 88 in VP3; 1, 148, 282 and 283 in VP1; 22 in 2A; 47 in 3A. A series of chimeric and point-mutated infectious clones were constructed to identify viral elements responsible for the distinct virulence. A single amino acid change from isoleucine to valine at position 88 in VP3 attenuated neurovirulence by reducing virus replication in the brain and spinal cord of infected mice. url: https://doi.org/10.3390/v12080867 doi: 10.3390/v12080867 id: cord-003961-gs75ebo4 author: Yin, Xin title: Hepatitis E Virus Entry date: 2019-09-20 words: 5141.0 sentences: 261.0 pages: flesch: 47.0 cache: ./cache/cord-003961-gs75ebo4.txt txt: ./txt/cord-003961-gs75ebo4.txt summary: The enteric route of transmission, EM evidence of naked virions in the feces, and the lack of coding capacity for envelope proteins all suggest that HEV is a nonenveloped virus. The enteric route of transmission, EM evidence of naked virions in the feces, and the lack of coding capacity for envelope proteins all suggest that HEV is a nonenveloped virus. However, recent studies show that the virus released from infected cells and circulating in the blood adopts a membrane associated, "quasienveloped" form, named "eHEV" [10, 11, 22] (Figure 1b ). However, recent studies show that the virus released from infected cells and circulating in the blood adopts a membrane associated, "quasienveloped" form, named "eHEV" [10, 11, 22] (Figure 1b ). The available evidence suggests that naked and quasienveloped HEV particles use different mechanisms for cell entry, and that entry of eHEV requires lysosomal degradation of the viral membrane. ORF3 protein of hepatitis E virus is essential for virion release from infected cells abstract: Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. It is transmitted enterically but replicates in the liver. Recent studies indicate that HEV exists in two forms: naked, nonenveloped virions that are shed into feces to mediate inter-host transmission, and membrane-cloaked, quasienveloped virions that circulate in the bloodstream to mediate virus spread within a host. Both virion types are infectious, but differ in the way they infect cells. Elucidating the entry mechanism for both virion types is essential to understand HEV biology and pathogenesis, and is relevant to the development of treatments and preventions for HEV. This review summarizes the current understanding of the cell entry mechanism for these two HEV virion types. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832200/ doi: 10.3390/v11100883 id: cord-309693-f2htekhz author: Yu, Meiling title: Immunogenicity of eGFP-Marked Recombinant Lactobacillus casei against Transmissible Gastroenteritis Virus and Porcine Epidemic Diarrhea Virus date: 2017-09-25 words: 5934.0 sentences: 234.0 pages: flesch: 45.0 cache: ./cache/cord-309693-f2htekhz.txt txt: ./txt/cord-309693-f2htekhz.txt summary: To develop an effective bivalent oral vaccine against TGEV and PEDV infection, the D antigenic site of the TGEV spike (S) protein and the major antigen site (core neutralizing epitope—COE) of the PEDV S protein were used as immunogens, and the enhanced green fluorescent protein (eGFP) gene was used as a reporter to construct genetically engineered Lactobacillus casei rLpPG(F)-T7g10-eGFP-6D-COE. The results showed that levels of anti-PEDV and anti-TGEV serum immunoglobulin G (IgG) and mucosal secreted immunoglobulin A (sIgA) antibodies obtained from the mice immunized with rLpPG(F)-T7g10-eGFP-6D-COE, as well as the proliferation levels of lymphocytes, were significantly higher than those in mice orally administered phosphate-buffered saline (PBS) or rLpPG-T7g10. This was evidenced by significantly higher levels of virus-neutralizing antibodies, anti-PEDV/TGEV serum IgG, and mucosal sIgA in mice orally immunized with rLpPG F -T7g10-eGFP-6D-COE, compared to the levels for the rLpPG-T7g10 or PBS groups. abstract: Porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) are the causative agents of highly fatal acute diarrhea in pigs, resulting in enormous losses in the pig industry worldwide. To develop an effective bivalent oral vaccine against TGEV and PEDV infection, the D antigenic site of the TGEV spike (S) protein and the major antigen site (core neutralizing epitope—COE) of the PEDV S protein were used as immunogens, and the enhanced green fluorescent protein (eGFP) gene was used as a reporter to construct genetically engineered Lactobacillus casei rLpPG(F)-T7g10-eGFP-6D-COE. The expression of proteins of interest by the recombinant L. casei was confirmed by confocal laser scanning microscopy and a Western blot assay, and the immunogenicity of rLpPG(F)-T7g10-eGFP-6D-COE in orally immunized mice was evaluated. The results showed that levels of anti-PEDV and anti-TGEV serum immunoglobulin G (IgG) and mucosal secreted immunoglobulin A (sIgA) antibodies obtained from the mice immunized with rLpPG(F)-T7g10-eGFP-6D-COE, as well as the proliferation levels of lymphocytes, were significantly higher than those in mice orally administered phosphate-buffered saline (PBS) or rLpPG-T7g10. Moreover, the serum IgG antibodies showed neutralizing effects against PEDV and TGEV. Our data suggest that the antibiotic resistance-free genetically engineered L. casei bivalent oral vaccine provides a safe and promising strategy for vaccine development against PEDV and TGEV. url: https://doi.org/10.3390/v9100274 doi: 10.3390/v9100274 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-326319-3538jmqd author: Yuan, Yuan title: Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins date: 2018-06-27 words: 7470.0 sentences: 370.0 pages: flesch: 54.0 cache: ./cache/cord-326319-3538jmqd.txt txt: ./txt/cord-326319-3538jmqd.txt summary: title: Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). At 14 dpv, IBV-specific antibody levels in birds immunized with subunit vaccines rHBM-S1-N, rHBM-S1, rHBM-N and inactivated vaccine strain H120 started to rise (p > 0.05). At 14 dpv, IBV-specific antibody levels in birds immunized with subunit vaccines rHBM-S1-N, rHBM-S1, rHBM-N and inactivated vaccine strain H120 started to rise (p > 0.05). Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus The S1 glycoprotein but not the N or M proteins of avian infectious bronchitis virus induces protection in vaccinated chickens abstract: Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which results in considerable economic losses. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing the S1 and N proteins and mono-expressing S1 or N proteins of the GX-YL5 strain of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels, as well as the percentages of CD4+ and CD8+ T lymphocytes, were detected within 28 days post-vaccination (dpv). The morbidity, mortality and re-isolation of the virus from the tracheas and kidneys of challenged birds were evaluated at five days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocytes were higher in the rHBM-S1-N vaccinated birds compared to birds vaccinated with the rHBM-S1 and rHBM-N vaccines. At 5 dpc, the mortality, morbidity and virus re-isolation rate of the birds vaccinated with the rHBM-S1-N vaccine were slightly higher than those vaccinated with the H120 control vaccine but were lower than those vaccinated with the rHBM-S1 and rHBM-N vaccines. The present study demonstrated that the protection of the recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing the S1 or N protein. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine. url: https://doi.org/10.3390/v10070347 doi: 10.3390/v10070347 id: cord-252466-usrpodjx author: Yun, Nadezhda E. title: Pathogenesis of Lassa Fever date: 2012-10-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents. url: https://doi.org/10.3390/v4102031 doi: 10.3390/v4102031 id: cord-311008-b7xjlqg3 author: Zapatero-Belinchón, Francisco J. title: Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors date: 2019-03-19 words: 10350.0 sentences: 556.0 pages: flesch: 52.0 cache: ./cache/cord-311008-b7xjlqg3.txt txt: ./txt/cord-311008-b7xjlqg3.txt summary: Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. The remarkable diversity of plasma membrane proteins implicated in filovirus cell entry prompted us to analyze twelve cell lines for a potential correlation of host factor expression to filovirus susceptibility. We could show that the neuroblastoma SH-SY5Y cell line is specifically resistant to filovirus infection although all intracellular proteins known to be essential were expressed, and although its overall transcriptome was very similar to that of susceptible cell lines. Heterokaryon assays revealed that SH-SY5Y cells did not express a dominant restriction factor that inhibited filovirus GP-driven cell entry, but recombinant GP could not bind to their plasma membrane. In SH-SY5Y cells, however, an ectopic expression of any potential attachment-promoting plasma membrane protein of filoviruses, such as DC-SIGN, Axl, Mer, or TIM-1, conferred susceptibility to filovirus GP-driven transduction or infection. abstract: Filoviruses infect a wide range of cell types with the exception of lymphocytes. The intracellular proteins cathepsin B and L, two-pore channel 1 and 2, and bona fide receptor Niemann–Pick Disease C1 (NPC1) are essential for the endosomal phase of cell entry. However, earlier steps of filoviral infection remain poorly characterized. Numerous plasma membrane proteins have been implicated in attachment but it is still unclear which ones are sufficient for productive entry. To define a minimal set of host factors required for filoviral glycoprotein-driven cell entry, we screened twelve cell lines and identified the nonlymphocytic cell line SH-SY5Y to be specifically resistant to filovirus infection. Heterokaryons of SH-SY5Y cells fused to susceptible cells were susceptible to filoviruses, indicating that SH-SY5Y cells do not express a restriction factor but lack an enabling factor critical for filovirus entry. However, all tested cell lines expressed functional intracellular factors. Global gene expression profiling of known cell surface entry factors and protein expression levels of analyzed attachment factors did not reveal any correlation between susceptibility and expression of a specific host factor. Using binding assays with recombinant filovirus glycoprotein, we identified cell attachment as the step impaired in filovirus entry in SH-SY5Y cells. Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. Our study reveals that a lack of attachment factors limits filovirus entry and provides direct experimental support for a model of filoviral cell attachment where host factor usage at the cell surface is highly promiscuous. url: https://www.ncbi.nlm.nih.gov/pubmed/30893855/ doi: 10.3390/v11030275 id: cord-003516-l1lq8yga author: Zhang, Jing title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations date: 2019-01-31 words: 2357.0 sentences: 133.0 pages: flesch: 38.0 cache: ./cache/cord-003516-l1lq8yga.txt txt: ./txt/cord-003516-l1lq8yga.txt summary: title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations A signature of these "old" HAdV-E4 is the absence of a critical replication motif, NF-I, which is found in all HAdV respiratory pathogens and most HAdVs. However, our recent survey of flu-like disease in children in Hong Kong reveals that the emergent HAdV-E4 pathogens circulating in civilian populations contain NF-I, indicating recombination and reflecting host-adaptation that enables the "new" HAdV-E4 to replicate more efficiently in human cells and foretells more potential HAdV-E4 outbreaks in immune-naïve civilian populations. Recent isolates are recombinants containing this HAdV replication motif [1] , presumably permitting an expansion of the virus range into the immune-naïve populations [5] [6] [7] [21] [22] [23] , and should be noted as a molecular evolution example of a post-zoonotic, host-adaptation of a "novel" and "emergent" human pathogen. abstract: Human adenovirus type 4 (HAdV-E4), which is intriguingly limited to military populations, causes acute respiratory disease with demonstrated morbidity and mortality implications. This respiratory pathogen contains genome identity with chimpanzee adenoviruses, indicating zoonotic origins. A signature of these “old” HAdV-E4 is the absence of a critical replication motif, NF-I, which is found in all HAdV respiratory pathogens and most HAdVs. However, our recent survey of flu-like disease in children in Hong Kong reveals that the emergent HAdV-E4 pathogens circulating in civilian populations contain NF-I, indicating recombination and reflecting host-adaptation that enables the “new” HAdV-E4 to replicate more efficiently in human cells and foretells more potential HAdV-E4 outbreaks in immune-naïve civilian populations. Special attention should be paid by clinicians to this emergent and recombinant HAdV-E4 circulating in civilian populations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410123/ doi: 10.3390/v11020129 id: cord-348968-0yoq0geu author: Zhang, Maodong title: Assessment of Metagenomic Sequencing and qPCR for Detection of Influenza D Virus in Bovine Respiratory Tract Samples date: 2020-07-28 words: 5718.0 sentences: 270.0 pages: flesch: 46.0 cache: ./cache/cord-348968-0yoq0geu.txt txt: ./txt/cord-348968-0yoq0geu.txt summary: The objective of this study was to assess the detection of influenza D virus (IDV) in bovine respiratory tract samples using two sequencing platforms (MiSeq and Nanopore (GridION)), and species-specific qPCR. In this study, IDV was used as a representative BRD-associated virus to examine the feasibility of using metagenomic sequencing for detection of viruses in clinical bovine respiratory samples. The proportion of viral reads per sample was 0.1% to 18.4% (Nanopore, WIMP analysis) compared to 0.03% to 3.1% for the previously generated MiSeq data; however, with both sequencing approaches, the majority of reads obtained were identified as host-derived or other (bacteria, fungi, unclassified) ( Figure 3 ). Taken together our results demonstrate the potential of metagenomic sequencing on the Illumina MiSeq and Oxford Nanopore platforms for detection of viruses, including IDV, in clinical samples from naturally infected animals with a wide range of viral loads. abstract: High throughput sequencing is currently revolutionizing the genomics field and providing new approaches to the detection and characterization of microorganisms. The objective of this study was to assess the detection of influenza D virus (IDV) in bovine respiratory tract samples using two sequencing platforms (MiSeq and Nanopore (GridION)), and species-specific qPCR. An IDV-specific qPCR was performed on 232 samples (116 nasal swabs and 116 tracheal washes) that had been previously subject to virome sequencing using MiSeq. Nanopore sequencing was performed on 19 samples positive for IDV by either MiSeq or qPCR. Nanopore sequence data was analyzed by two bioinformatics methods: What’s In My Pot (WIMP, on the EPI2ME platform), and an in-house developed analysis pipeline. The agreement of IDV detection between qPCR and MiSeq was 82.3%, between qPCR and Nanopore was 57.9% (in-house) and 84.2% (WIMP), and between MiSeq and Nanopore was 89.5% (in-house) and 73.7% (WIMP). IDV was detected by MiSeq in 14 of 17 IDV qPCR-positive samples with Cq (cycle quantification) values below 31, despite multiplexing 50 samples for sequencing. When qPCR was regarded as the gold standard, the sensitivity and specificity of MiSeq sequence detection were 28.3% and 98.9%, respectively. We conclude that both MiSeq and Nanopore sequencing are capable of detecting IDV in clinical specimens with a range of Cq values. Sensitivity may be further improved by optimizing sequence data analysis, improving virus enrichment, or reducing the degree of multiplexing. url: https://doi.org/10.3390/v12080814 doi: 10.3390/v12080814 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: 9294.0 sentences: 567.0 pages: flesch: 41.0 cache: ./cache/cord-011438-imbpgsub.txt txt: ./txt/cord-011438-imbpgsub.txt summary: Upon IAV infection, host innate immune system is triggered and activated to restrict virus replication and clear pathogens. 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. Host innate immunity, including phagocytic cells, interferons (IFNs), proinflammatory cytokines, etc., applies multiple mechanisms in defending IAV infection [105] . Influenza A virus nucleoprotein induces apoptosis in human airway epithelial cells: Implications of a novel interaction between nucleoprotein and host protein Clusterin Antiviral response elicited against avian influenza virus infection following activation of toll-like receptor (TLR)7 signaling pathway is attributable to interleukin (IL)-1β production The human interferon-induced MxA protein inhibits early stages of influenza A virus infection by retaining the incoming viral genome in the cytoplasm Cell death regulation during influenza A virus infection by matrix (M1) protein: A model of viral control over the cellular survival pathway 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-307110-eiobmxp2 author: Zhao, Shan title: Serological Screening for Coronavirus Infections in Cats date: 2019-08-13 words: 6732.0 sentences: 382.0 pages: flesch: 57.0 cache: ./cache/cord-307110-eiobmxp2.txt txt: ./txt/cord-307110-eiobmxp2.txt summary: In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Synthetic sequences of 12 coronavirus spike S1 subunits (HCoV-HKU1 (GB: YP_173238.1), MERS-CoV (GB:YP_009047204.1), SARS-CoV (GB: AAX16192.1), HCoV-OC43 (GB: AAR01015.1), HCoV-229E (GB: NP_073551.1), HCoV-NL63 (GB: YP_003767.1), TGEV (GB: ABG89325.1), PEDV (GB: AOG30832.1), BCoV (GB: P15777.1), PDCoV (GB: AML40825.1), FCoV type 1 (GB: FJ938060.1), FCoV type 2 (GB: AY994055.1)) and different domains of PEDV S1 subunit (S1 0 and S1 A-D , as identified and described in [40] ) were cloned into pCAGGS expression plasmids as described previously [41] . abstract: Coronaviruses (CoVs) are widespread among mammals and birds and known for their potential for cross-species transmission. In cats, infections with feline coronaviruses (FCoVs) are common. Several non-feline coronaviruses have been reported to infect feline cells as well as cats after experimental infection, supported by their ability to engage the feline receptor ortholog for cell entry. However, whether cats might become naturally infected with CoVs of other species is unknown. We analyzed coronavirus infections in cats by serological monitoring. In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Seventy-eight sera were positive for antibodies that recognized one or more coronavirus S1s whereas 1 serum exclusively reacted with human coronavirus 229E (HCoV-229E) and two sera exclusively reacted with porcine delta coronavirus (PDCoV). We observed antigenic cross-reactivity between S1s of type 1 and type 2 FCoVs, and between FCoV type 1 and porcine epidemic diarrhea virus (PEDV). Domain mapping of antibody epitopes indicated the presence of conserved epitope(s) particularly in the CD domains of S1. The cross-reactivity of FCoV type 1 and PEDV was also observed at the level of virus neutralization. To conclude, we provide the first evidence of antigenic cross-reactivity among S1 proteins of coronaviruses, which should be considered in the development of serological diagnoses. In addition, the potential role of cats in cross-species transmission of coronaviruses cannot be excluded. url: https://www.ncbi.nlm.nih.gov/pubmed/31412572/ doi: 10.3390/v11080743 id: cord-317026-9zgc6xrb author: Zhao, Shan title: Development and Validation of a S1 Protein-Based ELISA for the Specific Detection of Antibodies against Equine Coronavirus date: 2019-11-30 words: 6223.0 sentences: 317.0 pages: flesch: 55.0 cache: ./cache/cord-317026-9zgc6xrb.txt txt: ./txt/cord-317026-9zgc6xrb.txt summary: In this study, an indirect enzyme-linked immunosorbent assay (ELISA) method utilizing ECoV spike S1 protein was developed in two formats, and further validated by analyzing 27 paired serum samples (acute and convalescent sera) from horses involved in an ECoV outbreak and 1084 sera of horses with unknown ECoV exposure. On the other hand, serological assays can be used to support the diagnosis of a clinical ECoV infection by showing seroconversion or a significant increase in antibody titer in paired serum samples. For the six horses that did not show a significant rise in VNT, five serum samples collected at the acute stage already had high antibody levels as shown by ELISA and neutralization assay (mean OD value > 2.6, mean VNT > 9, Table S1 ). For the six horses that did not show a significant rise in VNT, five serum samples collected at the acute stage already had high antibody levels as shown by ELISA and neutralization assay (mean OD value > 2.6, mean VNT > 9, Table S1 ). abstract: Equine coronavirus (ECoV) is considered to be involved in enteric diseases in foals. Recently, several outbreaks of ECoV infection have also been reported in adult horses from the USA, France and Japan. Epidemiological studies of ECoV infection are still limited, and the seroprevalence of ECoV infection in Europe is unknown. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) method utilizing ECoV spike S1 protein was developed in two formats, and further validated by analyzing 27 paired serum samples (acute and convalescent sera) from horses involved in an ECoV outbreak and 1084 sera of horses with unknown ECoV exposure. Both formats showed high diagnostic accuracy compared to virus neutralization (VN) assay. Receiver-operating characteristic (ROC) analyses were performed to determine the best cut-off values for both ELISA formats, assuming a test specificity of 99%. Employing the developed ELISA method, we detected seroconversion in 70.4% of horses from an ECoV outbreak. Among the 1084 horse sera, seropositivity varied from 25.9% (young horses) to 82.8% (adult horses) in Dutch horse populations. Further, sera of Icelandic horses were included in this study and a significant number of sera (62%) were found to be positive. Overall, the results demonstrated that the ECoV S1-based ELISA has reliable diagnostic performance compared to the VN assay and is a useful assay to support seroconversion in horses involved with ECoV outbreaks and to estimate ECoV seroprevalence in populations of horses. url: https://www.ncbi.nlm.nih.gov/pubmed/31801275/ doi: 10.3390/v11121109 id: cord-003865-24lz9tf1 author: Zhou, Hongzhuan title: Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells date: 2019-08-13 words: 5582.0 sentences: 281.0 pages: flesch: 50.0 cache: ./cache/cord-003865-24lz9tf1.txt txt: ./txt/cord-003865-24lz9tf1.txt summary: To evaluate the antiviral effects of the three drugs of Nitazoxanide, Closantel Sodium and Closantel, F81 cells were seeded in 6-well plates at 7.5 × 10 5 cells per well and pretreated with the 3 drugs at a final concentrations of 5 µM, 10 µM, and 20 µM, respectively, for 1 h, then treated cells were infected with CPV at MOI of 0.076 as described above. As mentioned above, the identified drugs Nitazoxanide, Closantel Sodium, and Closantel can reduce the copy numbers of CPV viral DNA to 0.07%, 24.04%, and 20.83%, respectively, compared with the 0.1% DMSO-treated control ( Figure 3) . Our CPE-based screening assay showed that the percentage CPE inhibition of Oseltamivir and Cidofovir were 2.13 ± 2.41 and −1.28 ± 1.03 (Table S1 ), respectively, and that these two drugs had no anti-CPV effects on F81 cells. abstract: Canine parvovirus (CPV) is a common etiological agent of acute enteritis, which occurs globally in domestic and wild carnivores. Despite the widespread use of inactivated or live attenuated vaccines, the emergence of antigenic variants and the influence of maternal antibodies have raised some concerns regarding the efficacy of commercial vaccines. While no specific antiviral therapy for CPV infection exists, the only treatment option for the infection is supportive therapy based on symptoms. Thus, there is an urgent medical need to develop antiviral therapeutic options to reduce the burden of CPV-related disease. In this study, a cytopathic effect (CPE)-based high-throughput screening assay was used to screen CPV inhibitors from a Food and Drug Administration (FDA)-approved drug library. After two rounds of screening, seven out of 1430 screened drugs were found to have >50% CPE inhibition. Three drugs—Nitazoxanide, Closantel Sodium, and Closantel—with higher anti-CPV effects were further evaluated in F81 cells by absolute PCR quantification and indirect immunofluorescence assay (IFA). The inhibitory effects of all three drugs were dose-dependent. Time of addition assay indicated that the drugs inhibited the early processes of the CPV replication cycle, and the inhibition effects were relatively high within 2 h postinfection. Western blot assay also showed that the three drugs had broad-spectrum antiviral activity against different subspecies of three CPV variants. In addition, antiapoptotic effects were observed within 12 h in Nitazoxanide-treated F81 cells regardless of CPV infection, while Closantel Sodium- or Closantel-treated cells had no pro- or antiapoptotic effects. In conclusion, Nitazoxanide, Closantel Sodium, and Closantel can effectively inhibit different subspecies of CPV. Since the safety profiles of FDA-approved drugs have already been extensively studied, these three drugs can potentially become specific and effective anti-CPV drugs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724046/ doi: 10.3390/v11080742 id: cord-003962-lg6gvgwt author: Zhou, Shaochuan title: Characterizing the PRRSV nsp2 Deubiquitinase Reveals Dispensability of Cis-Activity for Replication and a Link of nsp2 to Inflammation Induction date: 2019-09-26 words: 10723.0 sentences: 517.0 pages: flesch: 56.0 cache: ./cache/cord-003962-lg6gvgwt.txt txt: ./txt/cord-003962-lg6gvgwt.txt summary: The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined. Further reverse genetics analyses revealed the following findings: (i) mutations that largely blocked the DUB activity were all lethal to the virus, (ii) a point mutation T88G that selectively blocked the cis-cleavage activity of PLP2 did not affect viral viability in cell culture, and (iii) an E90Q mutation that did not affect either of the PLP2 activities led to rescue of WT-like virus but displayed significantly reduced ability to induce TNF-α production. The results showed that the mutations of the residues D84 and E90 (e.g., D84N, D84R, E90R, E90Q, etc.) did not have much effect on PLP2 DUB activity, as the corresponding mutants could efficiently cleave K63 or K48 polyubiquitin chains into monomers ( Figure 4A , lanes 3, 4, 7, and 8). abstract: The papain-like cysteine protease 2 (PLP2) within the N-terminus of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp2 replicase protein specifies a deubiquitinating enzyme (DUB), but its biochemical properties and the role in infection have remained poorly defined. By using in vitro assays, we found that the purified PLP2 could efficiently cleave K63 and K48 linked polyubiquitin chains Ub3-7 in vitro although displaying a differential activity in converting the respective ubiquitin dimers to monomer. The subsequent mutagenesis analyses revealed that the requirement for PLP2 DUB activity surprisingly resembled that for cis-cleavage activity, as several mutations (e.g., D91R, D85R, etc.) that largely ablated the DUB function also blocked the cis- but not trans-proteolytic cleavage of nsp2/3 polyprotein. Moreover, the analyses identified key mutations that could differentiate DUB from PLP2 cis- and trans-cleavage activities. Further reverse genetics analyses revealed the following findings: (i) mutations that largely blocked the DUB activity were all lethal to the virus, (ii) a point mutation T88G that selectively blocked the cis-cleavage activity of PLP2 did not affect viral viability in cell culture, and (iii) an E90Q mutation that did not affect either of the PLP2 activities led to rescue of WT-like virus but displayed significantly reduced ability to induce TNF-α production. Our findings support the possibility that the PLP2 DUB activity, but not cis-cleavage activity, is essential for PRRSV replication. The data also establish a strong link of nsp2 to pro-inflammatory cytokine induction during infection that operates in a manner independent of PLP2 DUB activity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832237/ doi: 10.3390/v11100896 id: cord-352527-eeyqh9nc author: Zhou, Yusen title: Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain date: 2019-01-14 words: 5834.0 sentences: 277.0 pages: flesch: 44.0 cache: ./cache/cord-352527-eeyqh9nc.txt txt: ./txt/cord-352527-eeyqh9nc.txt summary: A number of MERS vaccines have been developed based on viral RBD, including nanoparticles, virus-like particles (VLPs), and recombinant proteins, and their protective efficacy has been evaluated in animal models, including mice with adenovirus 5 (Ad5)-directed expression of human DPP4 (Ad5/hDPP4), hDPP4-transgenic (hDPP4-Tg) mice, and non-human primates (NHPs) [88] [89] [90] [91] [92] [93] [94] . Receptor usage of a novel bat lineage C Betacoronavirus reveals evolution of Middle East respiratory syndrome-related coronavirus spike proteins for human dipeptidyl peptidase 4 binding Recombinant receptor-binding domains of multiple Middle East respiratory syndrome coronaviruses (MERS-CoVs) induce cross-neutralizing antibodies against divergent human and camel MERS-CoVs and antibody escape mutants A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein A novel nanobody targeting Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain has potent cross-neutralizing activity and protective efficacy against MERS-CoV abstract: Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy. url: https://www.ncbi.nlm.nih.gov/pubmed/30646569/ doi: 10.3390/v11010060 id: cord-314340-ltx4w9zh author: Zhu, Liqian title: The Involvement of Histone H3 Acetylation in Bovine Herpesvirus 1 Replication in MDBK Cells date: 2018-09-27 words: 6002.0 sentences: 282.0 pages: flesch: 44.0 cache: ./cache/cord-314340-ltx4w9zh.txt txt: ./txt/cord-314340-ltx4w9zh.txt summary: During bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures, partial of intranuclear viral DNA is present in nucleosomes, and viral protein VP22 associates with histones and decreases histone H4 acetylation, indicating the involvement of histone H4 acetylation in virus replication. In this study, we demonstrated that BoHV-1 infection at the late stage (at 24 h after infection) dramatically decreased histone H3 acetylation [at residues K9 (H3K9ac) and K18 (H3K18ac)], which was supported by the pronounced depletion of histone acetyltransferases (HATs) including CBP/P300 (CREB binding protein and p300), GCN5L2 (general control of amino acid synthesis yeast homolog like 2) and PCAF (P300/CBP-associated factor). Indeed, 5 µM of AA treatment could inhibit histone H3 acetylation as demonstrated by the reduced levels of H3K9ac relative to the control, but AA increased the levels of H3K9ac in the context of virus infection in comparison to the mock treated but infected cells ( Figure 3E ,F). abstract: During bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures, partial of intranuclear viral DNA is present in nucleosomes, and viral protein VP22 associates with histones and decreases histone H4 acetylation, indicating the involvement of histone H4 acetylation in virus replication. In this study, we demonstrated that BoHV-1 infection at the late stage (at 24 h after infection) dramatically decreased histone H3 acetylation [at residues K9 (H3K9ac) and K18 (H3K18ac)], which was supported by the pronounced depletion of histone acetyltransferases (HATs) including CBP/P300 (CREB binding protein and p300), GCN5L2 (general control of amino acid synthesis yeast homolog like 2) and PCAF (P300/CBP-associated factor). The depletion of GCN5L2 promoted by virus infection was partially mediated by ubiquitin-proteasome pathway. Interestingly, the viral replication was enhanced by HAT (histone acetyltransferase) activator CTPB [N-(4-Chloro-3-trifluoromethylphenyl)-2-ethoxy-6-pentadecylbenzamide], and vice versa, inhibited by HAT inhibitor Anacardic acid (AA), suggesting that BoHV-1 may take advantage of histone acetylation for efficient replication. Taken together, we proposed that the HAT-dependent histone H3 acetylation plays an important role in BoHV-1 replication in MDBK (Madin-Darby bovine kidney) cells. url: https://doi.org/10.3390/v10100525 doi: 10.3390/v10100525 id: cord-003697-vmmlxr0o author: Zhu, Yang title: Efficient Production of Human Norovirus-Specific IgY in Egg Yolks by Vaccination of Hens with a Recombinant Vesicular Stomatitis Virus Expressing VP1 Protein date: 2019-05-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Human norovirus (HuNoV) is responsible for more than 95% of outbreaks of acute nonbacterial gastroenteritis worldwide. Despite major efforts, there are no vaccines or effective therapeutic interventions against this virus. Chicken immunoglobulin Y (IgY)-based passive immunization has been shown to be an effective strategy to prevent and treat many enteric viral diseases. Here, we developed a highly efficient bioreactor to generate high titers of HuNoV-specific IgY in chicken yolks using a recombinant vesicular stomatitis virus expressing HuNoV capsid protein (rVSV-VP1) as an antigen. We first demonstrated that HuNoV VP1 protein was highly expressed in chicken cells infected by rVSV-VP1. Subsequently, we found that White Leghorn hens immunized intramuscularly with rVSV-VP1 triggered a high level of HuNoV-specific yolk IgY antibodies. The purified yolk IgY was efficiently recognized by HuNoV virus-like particles (VLPs). Importantly, HuNoV-specific IgY efficiently blocked the binding of HuNoV VLPs to all three types (A, B, and O) of histo-blood group antigens (HBGAs), the attachment factors for HuNoV. In addition, the receptor blocking activity of IgY remained stable at temperature below 70 °C and at pH ranging from 4 to 9. Thus, immunization of hens with VSV-VP1 could be a cost-effective and practical strategy for large-scale production of anti-HuNoV IgY antibodies for potential use as prophylactic and therapeutic treatment against HuNoV infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563233/ doi: 10.3390/v11050444 ==== 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