Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 129 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 7767 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 49 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 61 Fig 35 RNA 19 figure 18 IFN 17 virus 14 cell 10 SARS 6 MHV 5 dna 4 protein 3 viral 3 stat1 3 host 3 gene 3 TCR 3 SINV 3 RSV 3 MERS 3 IAV 3 HIV-1 3 HCV 3 GFP 3 Ebola 3 EV71 3 CoV 3 CHIKV 3 CD8 3 CD4 3 A59 2 sting 2 specie 2 pathogen 2 ie1 2 human 2 a549 2 WNV 2 VSV 2 VEEV 2 TBSV 2 PR8 2 PCR 2 PBS 2 ORF 2 Nipah 2 MHV-3 2 MDCK 2 IFITM3 2 HCMV 2 H5N1 2 Golgi Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 9431 cell 9052 virus 5400 protein 4120 infection 2332 % 2325 mouse 2283 replication 2046 gene 1960 host 1898 expression 1577 activity 1496 response 1483 analysis 1431 level 1415 sequence 1394 type 1392 antibody 1377 study 1364 receptor 1264 datum 1240 site 1180 figure 1153 structure 1140 genome 1071 role 1069 particle 1059 interaction 1029 membrane 1012 result 1008 control 996 region 985 assay 971 influenza 954 time 940 fusion 931 factor 908 disease 876 domain 869 sample 857 entry 851 pathway 850 mutation 848 effect 839 h 808 residue 806 day 795 coronavirus 791 - 754 acid 750 model Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 3404 Fig 3278 RNA 1248 IFN 891 SARS 856 C 722 T 632 MHV 599 PCR 564 CoV 483 L 483 HA 481 PBS 460 HCV 428 EV71 421 WT 393 A 389 S1 386 NA 375 VSV 367 F 361 S 355 Table 348 IAV 344 RSV 344 D 334 HIV-1 334 . 322 CHIKV 319 M 313 G 308 CD8 306 B 305 MOI 301 RT 298 pH 293 mRNA 291 S2 269 Figure 265 GFP 257 Virus 257 N 255 ATPase 254 WNV 249 K 247 GP 246 b 246 NP 238 HIV 237 p.i 233 DI Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 3798 we 1360 it 760 i 411 they 111 them 103 us 51 itself 27 ifitm3 21 themselves 21 one 16 you 13 isg20 11 imagej 9 mrnas 6 he 5 pdcs 4 had37 3 orf16 3 mg 3 isgf3 3 hek-293ts 1 ™ 1 yourself 1 yjbh. 1 usp21 1 type- 1 she 1 s 1 rptx3 1 rps11 1 rhptx3 1 rad5-hdpp4-shcd9 1 r170h 1 pro507 1 pp38-gfp 1 p9-met 1 p62 1 ourselves 1 ours 1 nsp3d 1 nsp15 1 nsp13/ 1 ns3/4a 1 npi64 1 nms-873 1 mrna7 1 mrna3 1 me 1 leu114 1 kp071471-kp071680 Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 29887 be 4067 use 3367 have 2062 show 1671 bind 1563 infect 1272 contain 1244 indicate 1216 determine 1193 induce 1113 do 1083 observe 1069 suggest 1052 follow 1012 describe 924 express 918 include 837 increase 830 perform 828 compare 797 require 768 identify 757 inhibit 755 find 754 associate 740 detect 727 mediate 671 reduce 656 provide 633 result 632 demonstrate 624 reveal 600 generate 585 base 564 treat 555 signal 552 incubate 513 encode 490 involve 481 report 481 know 470 lead 466 obtain 463 purify 458 affect 455 analyze 451 transfecte 447 regulate 439 activate 438 occur Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 3916 viral 2989 not 2599 - 1883 also 1609 human 1219 specific 1182 other 1100 high 918 different 912 well 904 more 872 however 868 cellular 866 anti 850 previously 838 only 807 low 761 immune 753 then 733 infected 704 similar 688 non 649 such 616 further 604 dependent 601 antiviral 585 most 574 thus 572 infectious 569 structural 569 respiratory 566 as 565 first 550 early 526 single 526 significant 519 wild 501 same 484 important 480 recombinant 477 functional 458 like 457 respectively 455 likely 454 several 453 significantly 450 negative 448 small 438 new 433 positive Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 194 most 141 least 84 high 41 large 40 good 37 Most 17 close 15 low 15 great 11 early 8 strong 8 long 7 small 6 short 4 farth 3 rep)RNA 3 fast 2 rcDNA 2 pdqu 2 near 2 late 2 fit 2 dark 1 wilcox_t 1 weak 1 vRNA 1 tt 1 simple 1 rich 1 old 1 nt9300 1 new 1 narrow 1 mild 1 leftmost 1 furth 1 exactt 1 dense 1 deep 1 deadly 1 dII 1 cord-266078-h53zpjab 1 big 1 W504 1 K33- 1 CpAM 1 -v 1 -proximal 1 --b Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 391 most 133 least 29 well 2 smallest 2 long 2 highest 1 v617ngly 1 rcdna 1 fast 1 .256-fold Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 58 doi.org 7 www 4 www.ebi.ac.uk 3 www.ncbi.nlm.nih.gov 2 www.sigmaaldrich.com 2 www.matrixscience.com 2 www.expasy.org 2 www.ambion.com 2 urldefense.proofpoint.com 2 rsbweb.nih.gov 1 zdock.bu.edu 1 www.uniprot.org 1 www.stratagene.com 1 www.spotfire.com 1 www.southernbiotech.com 1 www.rosettabio.com 1 www.rochediagnostics.com.au 1 www.roche-applied-science.com 1 www.qualitybiological.com 1 www.qiagen.com 1 www.poxvirus.org 1 www.pdbj.org 1 www.omni-inc.com 1 www.ncbi 1 www.nanodrop.com 1 www.malacards.org 1 www.kinematica.ch 1 www.ingenuity.com 1 www.informatics.jax.org 1 www.imgenex.com 1 www.ictvonline.org 1 www.graphpad 1 www.fludb.org 1 www.fermentas.com 1 www.expasy.ch 1 www.eppendorf.com 1 www.epibio.com 1 www.ebi.ac 1 www.dako.com 1 www.clontech.com 1 www.chemicon.com 1 www.ch.embnet.org 1 www.cbs.dtu.dk 1 www.cambrex 1 www.broadinstitute.org 1 www.bioinformatics.babraham.ac.uk 1 www.bioinformatics 1 www.bdbiosciences.com 1 www.atcc.org 1 www.amershambiosciences.com Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 7 http://www 1 http://zdock.bu.edu 1 http://www.uniprot.org/ 1 http://www.stratagene.com 1 http://www.spotfire.com/ 1 http://www.southernbiotech.com/ 1 http://www.sigmaaldrich.com/ 1 http://www.sigmaaldrich.com 1 http://www.rosettabio.com/ 1 http://www.rochediagnostics.com.au 1 http://www.roche-applied-science.com 1 http://www.qualitybiological.com 1 http://www.qiagen.com 1 http://www.poxvirus.org 1 http://www.pdbj.org/) 1 http://www.omni-inc.com 1 http://www.ncbi.nlm.nih.gov/gene 1 http://www.ncbi.nlm.nih.gov/Genbank 1 http://www.ncbi.nlm.nih.gov/ 1 http://www.ncbi 1 http://www.nanodrop.com 1 http://www.matrixscience.com/ 1 http://www.matrixscience.com 1 http://www.malacards.org 1 http://www.kinematica.ch 1 http://www.ingenuity.com/ 1 http://www.informatics.jax.org/ 1 http://www.imgenex.com/ 1 http://www.ictvonline.org 1 http://www.graphpad 1 http://www.fludb.org/ 1 http://www.fermentas.com 1 http://www.expasy.org/sprot/ 1 http://www.expasy.org/ 1 http://www.expasy.ch/ 1 http://www.eppendorf.com 1 http://www.epibio.com 1 http://www.ebi.ac.uk/pdbe/prot_int/pistart.html 1 http://www.ebi.ac.uk/pdbe/prot_ 1 http://www.ebi.ac.uk/Tools/sss/ 1 http://www.ebi.ac.uk/ 1 http://www.ebi.ac 1 http://www.dako.com/ 1 http://www.clontech.com 1 http://www.chemicon.com 1 http://www.ch.embnet.org/software/ClustalW.html 1 http://www.cbs.dtu.dk/services/ 1 http://www.cambrex 1 http://www.broadinstitute.org/igv/ 1 http://www.bioinformatics.babraham.ac.uk/projects/ Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 70 cells were then 20 virus infected cells 16 cells were co 16 cells were transiently 15 virus inhibits dna 13 replication was not 10 cells were also 10 cells were mock 10 cells were pre 10 expression was also 9 cells was not 9 rna was then 8 receptor binding protein 7 cells do not 7 cells is not 7 mice did not 7 mice were not 7 rna binding proteins 7 virus was also 7 virus was not 6 cells did not 6 cells expressing gfp 6 cells were first 6 data are representative 6 infection is not 6 levels were significantly 6 receptor binding domain 5 cells are not 5 cells were subsequently 5 data provide evidence 5 expression is not 5 expression was not 5 infection does not 5 infection was also 5 levels were not 5 receptor binding proteins 5 virus binding rate 5 viruses did not 5 viruses is likely 4 activity is essential 4 activity is not 4 cells expressing wt 4 cells were either 4 cells were further 4 expression using flow 4 genes were not 4 infection has not 4 infection is also 4 infection was not 4 mice were also Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 4 infection is not clear 2 cells is not due 2 expression was not due 2 mice were not significantly 2 proteins was not due 1 activity had not much 1 activity has not yet 1 activity is not as 1 activity is not essential 1 activity was not significantly 1 analysis is not well 1 analysis provided no evidence 1 analysis showed no co 1 antibodies had no effect 1 antibody was not significantly 1 cells did not significantly 1 cells has not yet 1 cells is not easily 1 cells was not reproducible 1 cells were not thermolysin 1 data contained no evidence 1 expression have not yet 1 expression is not rate 1 expression was not impaired 1 expression was not substantially 1 gene are not likely 1 genes are not de 1 genes are not spatially 1 genes were not close 1 genes were not even 1 genome had not yet 1 genome is not heavily 1 host has not yet 1 infection do not spontaneously 1 infection does not drastically 1 infection does not formally 1 infection is not presently 1 infection was no longer 1 infections are not fully 1 infections is not well 1 interactions are not only 1 levels were not significant 1 mice are not more 1 mice is not due 1 mice were not different 1 particles are not empty 1 particles are not naked 1 particles has no sign 1 particles showed no apparent 1 protein is not directly A rudimentary bibliography -------------------------- id = cord-267149-5twx9y5c author = Abraham, Jonathan title = Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses date = 2009-04-03 keywords = AMAV; TCRV; human summary = doi = 10.1371/journal.ppat.1000358 id = cord-269466-9hnal9ad author = Agbeci, Maxime title = Contribution of Host Intracellular Transport Machineries to Intercellular Movement of Turnip Mosaic Virus date = 2013-10-03 keywords = Fig; RNA; movement summary = In this study, we used a novel dual gene cassette construct that differentiated primary infected cells from cells infected after virus intercellular movement to show that the early as well as the late secretory pathway, but not endocytosis, was important for TuMV transport. By using a dual cassette of genes encoding fluorescent proteins that can differentiate between primary infected cells and cells infected after intercellular transport, we provide evidence that turnip mosaic virus (TuMV) needs a functional secretory pathway where pre-and post-Golgi trafficking and the actomyosin network are important for its movement. Fig. 2E shows that that there was no significant difference in the ratio of red over green fluorescence during BFA and CMA treatments compared with the no inhibitor treatment (TuMV alone) at 4 dpinf, indicating that viral protein production in the primary infected cells was not affected by the drug treatments. doi = 10.1371/journal.ppat.1003683 id = cord-001859-d62iuk72 author = Baquero-Pérez, Belinda title = Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments date = 2015-11-20 keywords = BCBL1-RTA; DMSO; Fig; Hsc70; KSHV; RTA; dna summary = Similar Hsc70 localization was seen during early lytic replication (12 h reactivation), when RTA protein was diffuse in the nucleus, Successful enrichment of the nuclear envelope region and associated KSHV RTCs in HEK-293T rKSHV.219 cells. These results clearly demonstrate that KSHV specifically redistributes the molecular chaperones, Hsc70 and iHsp70, from the cytoplasm to the nucleus, in contrast to Grp78, which coincides with the initial formation of KSHV RTCs. Treatment with the small molecule inhibitor VER-155008 abrogated viral protein synthesis at non-cytotoxic concentrations Members of the HSP70 chaperone family possess an N-terminal nucleotide binding domain with ATPase activity which is essential for their function. Therefore to ascertain whether Hsp70 isoforms could stabilise the essential KSHV lytic proteins RTA and ORF57, TREx BCBL1-RTA cells were reactivated for 24 h to allow sufficient viral protein expression followed by addition of DMSO control or VER-155008 in conjunction with cycloheximide (CHX) at 50 μg/ml to block de novo protein synthesis. doi = 10.1371/journal.ppat.1005274 id = cord-325326-2bbqz4o7 author = Beitzel, Brett F. title = High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing date = 2010-10-14 keywords = RNA; Sindbis; VEEV; insertion; virus summary = We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. Toward this goal, we used transposon mutagenesis, reverse genetics, and fragment analysis by capillary electrophoresis to identify regions of the nsP3 gene that are important for replication and that result in temperature sensitive (ts) mutations. We used transposon mutagenesis to construct a cDNA library with small DNA fragments randomly inserted throughout the VEEV genome and then produced replication-competent virus through reverse genetics. Comparing transposon insertion sites in the resultant viruses to those in the starting library, we were able to produce a functional map of the entire genome of VEEV, and to identify several hundred potential ts mutations, including those we originally identified with the capillary electrophoresis method. doi = 10.1371/journal.ppat.1001146 id = cord-001636-khrx6rnh author = Bordería, Antonio V. title = Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype date = 2015-05-05 keywords = DAF; E76; Fig; a549 summary = The total number of minority variants within the P1 structural coding region also significantly increased over the passage series (Fig 1G) , yet there were no significant differences between the numbers observed in Hela and A549 cell passage. The mutations that arise from adaptive passage map to receptor binding sites in a cell-type specific manner Although the HeLa and A549 cell passage series presented similar mean genetic diversity at passage 40 (Fig 1E-1G , P = 0.314), we mined the deep sequence data for all minority variants above 1% frequency that might explain adaptation in each condition (Table 1 ). Given the different frequencies of minority variants observed at passage 40, we examined the patterns of emergence and sequential adaptation to novel environments by deep sequencing every second passage in the A549 cell series (Fig 3 and S1 Dataset). doi = 10.1371/journal.ppat.1004838 id = cord-312743-9e4yufo5 author = Breiman, Adrien title = Harnessing the natural anti-glycan immune response to limit the transmission of enveloped viruses such as SARS-CoV-2 date = 2020-05-21 keywords = SARS summary = These observations suggested that, when produced in cells that express the A or B blood group enzymes, infectious SARS virions are decorated by the corresponding glycan antigens and that the presence of anti-A and anti-B antibodies in blood group O individuals could prevent infection by blocking virus attachment and entry. We therefore hypothesize that as they are produced in cells coexpressing the ACE2 receptor and either the αGal, NeuGc, or A/B blood group antigens, both SARS-CoV and SARS-CoV2 harbor the corresponding glycan epitopes. Likewise, impairment of transmission by the anti-blood group antibodies may not work to its full potential because of their variable titers in the population and of the high affinity of the SARS-CoV2 for ACE2 [18] , rendering its neutralization more difficult. doi = 10.1371/journal.ppat.1008556 id = cord-321874-eenaixp0 author = Brennan, Greg title = Adaptive Gene Amplification As an Intermediate Step in the Expansion of Virus Host Range date = 2014-03-13 keywords = Fig; HFF; PKR; pro1190 summary = doi = 10.1371/journal.ppat.1004002 id = cord-000007-h8upyzb1 author = Butler, Noah S. title = Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant date = 2008-10-24 keywords = CTL; Q600Y; S598; figure summary = Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Enhancement strategies, which result in augmented responses to the native, subdominant epitope, have been described for both MHC class I and class II-restricted determinants, whereby the most common approaches involve generating a series of conserved and non-conserved mutations at MHC anchor residues, followed by an empiric determination of whether each individual substitution augments T cell effector function [12] . Immunization with the modified peptide resulted in an improved response to the native S598 epitope, demonstrating a true heteroclitic effect and suggesting that this strategy may have clinical applications for reducing viral titer and preventing CTL escape during chronic infections. Seven days following virus infection, brains were harvested from mice and the frequencies of epitope-specific CD8 T cells were determined by ex vivo stimulation and intracellular cytokine staining as described above. doi = 10.1371/journal.ppat.1000186 id = cord-001082-sufwsu77 author = Bär, Séverine title = Vesicular Transport of Progeny Parvovirus Particles through ER and Golgi Regulates Maturation and Cytolysis date = 2013-09-19 keywords = Fig; Golgi; MVM summary = doi = 10.1371/journal.ppat.1003605 id = cord-000103-3zh8jmc2 author = Caignard, Grégory title = Differential Regulation of Type I Interferon and Epidermal Growth Factor Pathways by a Human Respirovirus Virulence Factor date = 2009-09-18 keywords = EGF; ERK; GRB2; IFN; stat1 summary = doi = 10.1371/journal.ppat.1000587 id = cord-321957-ybtk9cp1 author = Carey, Brian D. title = Protein Kinase C subtype δ interacts with Venezuelan equine encephalitis virus capsid protein and regulates viral RNA binding through modulation of capsid phosphorylation date = 2020-03-09 keywords = CPD; Fig; RNA; TC-83; VEEV summary = doi = 10.1371/journal.ppat.1008282 id = cord-262248-q5eijunp author = Casadevall, Arturo title = The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases date = 2015-04-23 keywords = Ebola summary = Currently, there are no drugs to treat Ebola, but, in the urgency and emergency triggered by the epidemic, two types of Ab-based therapies have been used: convalescent sera from patients who have recovered and a mAb cocktail known as ZMapp produced in plants [3] . For example, given that there is increasing evidence that antibiotic-induced disruptions of the microbiota are associated with deleterious effects in the treatment of bacterial diseases, the high specificity of Ab-based therapies offers a tremendous advantage. Regarding the limitation that highly specific Abs can fail to bind highly related variants, particularly for viruses, there are two strategies to overcome this problem: the development of Abs that target broadly neutralizing epitopes, as has now been demonstrated for HIV [8] , dengue [9] , and influenza viruses [10] , and the generation of Ab cocktails composed of Abs against multiple serotypes or variants, as has been done for rabies virus [11] and Clostridium difficile toxin [12] . doi = 10.1371/journal.ppat.1004717 id = cord-000025-6zrv687k author = Chachu, Karen A. title = Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection date = 2008-12-12 keywords = CD4; CD8; figure; mnv summary = In the absence of a cell culture system for HuNV, virus like particles (VLPs) that assemble when the viral capsid protein is expressed have been important for evaluating norovirus immune responses [20] [21] [22] [23] . To determine the role of T cells in clearance of acute MNV infection we inoculated WT, MHC Class II-/-, and MHC Class I6b2M-/-mice orally with MNV1.CW3 and measured viral titers in the distal ileum and MLN three, five, seven and 21 days post-infection ( Figure 4B-4E) . Together, these data from primary challenges of non-immune mice lacking antigen presenting molecules or depleted of specific T cell subsets demonstrated that CD4 T cells are important for efficient MNV clearance in the distal ileum especially at days three Lack of any of the three components of the adaptive response: B cells, CD4 T cells, or CD8 T cells significantly diminished vaccine effects generated by either live virus or VP1 capsid protein immunization, and delayed viral clearance during primary infection. doi = 10.1371/journal.ppat.1000236 id = cord-000409-lpf9lpky author = Chen, Yongwen title = Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection date = 2011-07-07 keywords = FGL2; IFN; MHV-3; PD-1 summary = Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. In all, these results demonstrated that PD-1 deficiency led to enhanced pathological damage by MHV-3 in the liver, spleen, lymph node and thymus, where higher levels of PD-1-positive cells were found after infection. Results showed that the expression of FGL2 was principally associated with CD31-positive endothelial cells, CD68-positive macrophages and CD11c-positive DCs. Surprisingly, significantly higher levels of FGL2 were observed after infection in all of PD-1-deficient organs, including the liver, thymus, spleen, lymph nodes, and serum than that in those from WT littermates. However, the number of Foxp3-positive cells in the liver, spleen, lymph node or thymus was not significantly different between PD-1-deficient mice and their WT littermates after 72 h of MHV-3 infection (Fig. S3) . doi = 10.1371/journal.ppat.1001347 id = cord-297702-vxcj25sn author = Chen, Yuxin title = A comprehensive, longitudinal analysis of humoral responses specific to four recombinant antigens of SARS-CoV-2 in severe and non-severe COVID-19 patients date = 2020-09-10 keywords = SARS; covid-19 summary = We continuously monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the nucleoprotein (NP), receptor binding domain (RBD), S1 protein, and ectodomain (ECD) of the spike protein among non-severe and severe COVID-19 patients for seven weeks since disease onset. In this retrospective study, we successively monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the NP protein, RBD protein, S1 protein, and ECD protein in 19 non-severe and 7 severe COVID-19 patients during the disease progression. The severe patients and non-severe patients had comparable reduced fold of IgM, IgG, and IgA binding titer specific to RBD, ECD, S1, and NP protein and neutralization activities. Furthermore, 80.7% of the convalescent sea from COVID-19 patients displayed varying levels of neutralization activities against SARS-CoV-2, which correlated with S1-specific and ECD-specific IgA responses in non-severe patients. doi = 10.1371/journal.ppat.1008796 id = cord-316999-712rit8h author = Chinchio, Eleonora title = Invasive alien species and disease risk: An open challenge in public and animal health date = 2020-10-22 keywords = IAS; pathogen; specie summary = doi = 10.1371/journal.ppat.1008922 id = cord-342291-imn7g084 author = Ciminski, Kevin title = Bats reveal the true power of influenza A virus adaptability date = 2020-04-16 keywords = New; World summary = Indeed, the HA of the newly discovered Old World bat H9N2 virus binds to α2,3-sialic In contrast, the internal gene segments of the bat-derived IAVs form two outgroups that are located at a more basal position. Conventional IAVs and the bat H9N2 virus possess the surface glycoprotein neuraminidase (NA), which removes sialic acid residues from infected cells to facilitate the release of newly formed viral particles (Fig 2A) . The amazing ability of H18 to rapidly overcome the absence of a functional N11 suggests that the structure of H18 (and possibly H17) may provide a broader scope of evolutionary flexibility than that of conventional sialic acid-dependent IAVs. It is therefore tempting to speculate that bat IAV HA proteins, and in particular H18, might have the potential to adapt to novel and so far unknown entry receptors different from MHC-II (Fig 2D) . doi = 10.1371/journal.ppat.1008384 id = cord-000232-boto4h8x author = Danthi, Pranav title = Bid Regulates the Pathogenesis of Neurotropic Reovirus date = 2010-07-01 keywords = Bid; TRAIL; figure; reovirus summary = Blockade of NF-kB signaling, which diminishes apoptosis induction by reovirus [8, 28] , prevents cleavage of Bid. In comparison to wild-type mice, Bid-deficient mice display diminished susceptibility to reovirus-induced CNS disease following either peroral (PO) or intracranial (IC) inoculation. To directly test whether Bid is required for apoptosis induction following reovirus infection, we compared reovirus-induced apoptosis in wild-type and Bid-deficient MEFs. For these experiments, MEFs were infected with T3D, and apoptosis was assessed by chemiluminescent measurement of the activity of caspase-3 and caspase-7, which serve as effector caspases for both the extrinsic and intrinsic apoptotic pathways ( Figure 2A ). Increase in caspase-3/7 activity following treatment of each cell type with a broad-spectrum protein kinase inhibitor, staurosporine, was equivalent (,5-fold), demonstrating that although Bid-deficient cells possess functional death-signaling pathways, they resist apoptosis induction by reovirus. Analogous to treatment with TNFa, a control NF-kB agonist, reovirus infection resulted in equivalent (,2-to 3-fold) activation of NF-kB-driven gene expression in wild-type and Bid-deficient cells ( Figure 3A ). doi = 10.1371/journal.ppat.1000980 id = cord-000127-tkxpjlyn author = Dermody, Terence S. title = Immunoglobulin Superfamily Virus Receptors and the Evolution of Adaptive Immunity date = 2009-11-26 keywords = jam summary = The immunoglobulin superfamily (IgSF) of molecules contains several members that are expressed at the cell surface, bind diverse ligands, and contribute to a variety of cellular activities, including adhesion and immune responses. While structural information about com-plex formation is lacking for the IgSF receptors carcinoembryonic antigen-related cell adhesion molecule, nectin-1, nectin-2, and signaling lymphocyte-activation molecule (SLAM), biochemical studies also implicate their respective D1 domains in virus binding [11] [12] [13] [14] . The evolution of JAM family members prior to the biochemical means to efficiently and extensively diversify antigen receptor genes, along with the structural similarities in the binding surfaces of virus receptors and immunoglobulins, provides strong support for the contention that viruses and perhaps other pathogens that engage IgSF receptors contributed to the selection of humoral mediators of adaptive immunity. doi = 10.1371/journal.ppat.1000481 id = cord-325192-italbsed author = Desai, Tanay M. title = IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion date = 2014-04-03 keywords = Fig; IAV; IFITM3; MDCK; a549; cell summary = Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. Our results show that IFITM3 does not inhibit the lipid mixing stage of IAV fusion but blocks the release of viral contents into the cytosol, and that this phenotype does not correlate with cholesterol accumulation in intracellular compartments. Our results thus demonstrate that IFITM3 restricts the IAV fusion at a post-hemifusion step, most likely at the point of fusion pore opening, as evidenced by the dramatic decrease of the BlaM signal in A549 and MDCK cells expressing this protein (Fig. 1A ). Neither IAV lipid mixing (vDiD dequenching) nor fusion (BlaM signal) was inhibited by silencing NPC1 in A549 cells (Fig. 5E, F) . doi = 10.1371/journal.ppat.1004048 id = cord-263239-andje0wu author = Dorobantu, Cristina M. title = Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus date = 2015-09-25 keywords = EMCV; Fig; OSBP; PI4KA; PI4P; RNA summary = doi = 10.1371/journal.ppat.1005185 id = cord-265947-7j9qqi8w author = Du, Wenjuan title = The 2(nd) sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance date = 2019-06-10 keywords = 2SBS; Fig summary = NAs of avian, but not human viruses, contain a functional 2(nd) sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. Using a recently established BLI-based kinetic binding assay [37] an enhanced initial binding rate to 3''SLNLN but not 6''SLNLN ( Fig 4A and 4B ), was observed for hH3aN2 virus containing Role for 2 nd SIA-binding site of IAV NA in HA-NA-receptor balance a functional 2SBS in comparison to hH3hN2. We therefore studied the effect of the 2SBS in NA when combined with an avian-type Role for 2 nd SIA-binding site of IAV NA in HA-NA-receptor balance HA preferring binding to α2,3-linked SIAs. We generated the corresponding recombinant A/ Hong Kong/1/68 (H3N2) viruses containing 7 amino acid substitutions in the HA (see S8A Fig) . doi = 10.1371/journal.ppat.1007860 id = cord-011380-kfkp1zpn author = Duru, Adil Doganay title = Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination date = 2020-05-04 keywords = CD8; H-2D; P14; TCR summary = doi = 10.1371/journal.ppat.1008244 id = cord-309056-ul9q3ebx author = Dutch, Rebecca Ellis title = Entry and Fusion of Emerging Paramyxoviruses date = 2010-06-24 keywords = Nipah summary = doi = 10.1371/journal.ppat.1000881 id = cord-003441-810r5q03 author = Dzimianski, John V. title = Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity date = 2019-01-10 keywords = CCHFV; FARV; Fig; K48; QYBV; votu summary = Specifically, that CCHFV vOTU DUB activity is not as promiscuous towards ubiquitinated host proteins as it first seemed based on the overexpression studies, but appears to be restricted to a targeted subset of cellular substrates associated with suppression of RIG-I-mediated early cellular responses to infection. Additionally, a structure of the FARV vOTU provides details into the structural nature of the additional residues in Hughes orthonairovirus vOTUs. Structureinformed mutagenesis of FARV vOTU identified residues involved specifically in di-Ub binding, representing the first report of the role of a second site involved in di-Ub binding in nairovirus vOTUs. This novel enzymatic and structural data not only provides insight into the nature of vOTU diversity, but also lays a foundation for understanding the impact of the vOTU interaction with the innate immune response and its connection to viral pathogenesis. Intriguingly, the vOTUs showed a diverse range of activity towards Ub. In general, vOTUs can be divided into groups possessing high (CCHFV, HAZV, NSDV/GANV, TAGV), moderate (DUGV, KUPEV, FARV, QYBV, ISKV), or low activity (ERVEV, DGKV, LPHV, HpTV-1) (Fig 2A) . doi = 10.1371/journal.ppat.1007515 id = cord-315316-w7cn9iqp author = Earnest, James T. title = The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases date = 2017-07-31 keywords = CD9; DPP4; Fig; MERS; TMPRSS2; cell summary = doi = 10.1371/journal.ppat.1006546 id = cord-002125-anp238gu author = Effantin, Grégory title = Cryo-electron Microscopy Structure of the Native Prototype Foamy Virus Glycoprotein and Virus Architecture date = 2016-07-11 keywords = Env; Fig; Gag; PFV summary = Mature PFV particles have a distinct morphology with a capsid of constant dimension as well as a less ordered shell of density between the capsid and the membrane likely formed by the Gag N-terminal domain and the cytoplasmic part of the Env leader peptide gp18(LP). In order to obtain structural insight into PFV organization at medium resolution we used cryo-electron tomography (cryo-ET) and microscopy (cryo-EM) to analyze isolated wild-type particles and variants with mutations in PFV Gag and Env proteins. To gain more insights into the structure of the PFV glycoprotein, we use 3D reconstructions of iNAB and iFuse Env hexagonal assemblies of six trimers determined by subtomogram averaging as initial references for automatic particle selection of micrographs acquired by cryo-EM (S4 Fig) (see Material and Methods). doi = 10.1371/journal.ppat.1005721 id = cord-338400-30vl2hks author = Epstein, Jonathan H. title = Identification of GBV-D, a Novel GB-like Flavivirus from Old World Frugivorous Bats (Pteropus giganteus) in Bangladesh date = 2010-07-01 keywords = GBV; bat; virus summary = Phylogenetic analysis indicates that this first GBV-like flavivirus reported in bats constitutes a distinct species within the Flaviviridae family and is ancestral to the GBV-A and -C virus clades. GBV-A viruses have been described in New World primates and are not known to infect humans [17] [18] [19] , while GBV-C (also known as Hepatitis G virus (HGV)) have frequently been isolated from humans in many regions of the World, including India and Bangladesh [19] [20] [21] [22] [23] , and from wild chimpanzees (Pan troglodytes) in Africa [24, 25] . Our findings provide new insight into the range of known hosts for GB-like viruses and demonstrate the power of unbiased sequencing to characterize the diversity of potentially zoonotic pathogens carried by bats and other reservoirs. Molecular analyses of sera from Pteropus giganteus bats from Faridpur, Bangladesh led to the identification of a 9,633 nt sequence consistent in genomic organization with known GBV and other species within the family Flaviviridae [16] . doi = 10.1371/journal.ppat.1000972 id = cord-302340-pw2xqhwa author = Feeley, Eric M. title = IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry date = 2011-10-27 keywords = Fig; IFITM3; IFN; MDCK; cell summary = doi = 10.1371/journal.ppat.1002337 id = cord-000660-tsvzg0ax author = Fensterl, Volker title = Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis date = 2012-05-17 keywords = IFN; RNA; VSV; figure; ifit2 summary = doi = 10.1371/journal.ppat.1002712 id = cord-338053-8zlxsf1z author = Foo, Suan-Sin title = Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation date = 2015-02-19 keywords = Fig; HEK; PTX3; RRV summary = In summary, our data demonstrated the crucial role of PTX3 in modulating alphavirus-induced immune responses and disease manifestation through its N-terminal interaction with the virus particles leading to enhanced viral entry and replication. To confirm that the results of enhanced virus production was due to PTX3 enhancing RRV replication, HEK 293T cells transiently transfected with vector or hPTX3 plasmids were harvested at 20 hour post transfection (hpt) ( To further characterize the effect of PTX3 during alphaviral infection, we examined the potential of PTX3 to directly interact with the virus and enhance viral entry. To demonstrate that the effect of PTX3on enhancing RRV entry and replication contributed to the increased level of virus detected in the in vivo studies, we performed RRV infection on primary fibroblasts isolated from tails of PTX3 -/and WT C57BL/6 mice. doi = 10.1371/journal.ppat.1004649 id = cord-001700-c6elsnag author = Fusco, Marnie L. title = Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs date = 2015-06-26 keywords = Ebola; Fig; MARV; Ravn summary = Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. To generate MARV GP-specific mAbs, BALB/c mice were immunized with GPΔmuc antigens from either MARV strain Ci67, Musoke, Angola, or Ravn ( Fig 1A) . To characterize the binding of mAbs, we performed enzyme-linked immunosorbent assays (ELISAs) with recombinant GPs from four MARV strains, and determined EC50 values for binding with different forms of MARV Ravn GP: GP, GPΔmuc, GPcl (Fig 2A) . Two of the highly cross-reactive MARV antibodies, mAbs 40G1 and 2D8, also exhibit binding to Ebola, Sudan, Bundibugyo and Reston virus mucin-deleted GPs by ELISA (Fig 5A) . doi = 10.1371/journal.ppat.1005016 id = cord-275307-d7htyfcl author = Gaglia, Marta Maria title = Transcriptome-Wide Cleavage Site Mapping on Cellular mRNAs Reveals Features Underlying Sequence-Specific Cleavage by the Viral Ribonuclease SOX date = 2015-12-08 keywords = Fig; GFP; RNA; SOX; cut; site summary = doi = 10.1371/journal.ppat.1005305 id = cord-260949-w2xuf15h author = Galluzzi, Lorenzo title = Viral Control of Mitochondrial Apoptosis date = 2008-05-30 keywords = Bak; Bax; Bcl-2; MMP; PTPC; apoptosis; cell; protein summary = Bcl-2/Bcl-X L stabilizes mitochondrial membranes via multiple mechanisms, including (1) the sequestration into inactive complexes of its proapoptotic counterparts, Bax, Bak, and BH3only proteins (e.g., Bid) (for review: [S65,S78]), (2) inhibitory interactions with PTPC constituents, in particular with VDAC and the adenine nucleotide translocase (ANT) [12, 14] , (3) an enhancement of Cyt c oxidase activity and mitochondrial respiration [S79], and/or (4) indirect effects on intracellular Ca 2+ stores of the ER [S80,S81]. With regard to this, viral factors can be classified into one of the four following subgroups: proapoptotic proteins (1) that insert into mitochondrial membranes and hence trigger MMP through the action of amphipathic a-helical domains or (2) that promote MMP indirectly, through the activition of host-encoded factors (Table 1) , and antiapoptotic modulators (3) that exhibit sequence and/or structural similarity to multidomain BH1-4 members of the Bcl-2 family (so-called viral Bcl-2 proteins [vBcl-2s]) or (4) that inhibit apoptosis via other mechanisms (Table 2) . doi = 10.1371/journal.ppat.1000018 id = cord-353703-u86ggw11 author = Gao, Peng title = Reprogramming the unfolded protein response for replication by porcine reproductive and respiratory syndrome virus date = 2019-11-18 keywords = ATF4; Fig; GRP78; PRRSV; RNA; UPR summary = doi = 10.1371/journal.ppat.1008169 id = cord-281404-5a8au32c author = Gastaldello, Stefano title = Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells date = 2013-10-10 keywords = BPLF1; EBV; bx1; dna; figure summary = The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Here we report that induction of the productive virus cycle has no appreciable effects on the global levels of protein ubiquitination but is accompanied by a BPLF1-dependent decrease of cullin neddylation and stabilization of nuclear CRL substrates. The Akata-Bx1 cell line was used to study the contribution of the Ub-and NEDD8-specific deconjugase activities of the EBV large tegument protein BPLF1 to the productive virus cycle. In order to assess whether this regulatory interaction may operate during virus replication, the productive cycle was induced in Akata-Bx1 cells transiently transfected with plasmids expressing Myc-tagged CAND1 or the CAND1 Nterminus that compete for BPLF1 binding to cullins, or, as controls, the CAND1 C-terminus that binds to the opposite end of the cullin scaffold, and the empty vector ( Figure 5A ). doi = 10.1371/journal.ppat.1003664 id = cord-304747-ojyxs3cp author = Gaynor, Anne M title = Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections date = 2007-05-04 keywords = SV40; virus summary = doi = 10.1371/journal.ppat.0030064 id = cord-287219-qxkwjkif author = Geisbert, Thomas W. title = Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates date = 2008-11-28 keywords = Ebola; VSVDG; ZEBOV; ZEBOVGP summary = In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). Therefore, we conducted a study to assess the pathogenicity and protective efficacy of the recombinant VSVbased ZEBOV vaccine vector in rhesus macaques that were infected with simian-human immunodeficiency virus (SHIV) which is known to deplete the populations of naive CD4+ T cells, naive CD8+ T cells, and memory CD4+ T cells in these animals [22, 23] . Disease progressed in two of the VSVDG/ZEBOVGP-vaccinated SHIV-infected monkeys (Subject #5 and 6) and both of the placebo control animals with the development of additional evidence of clinical illness including increased levels of serum enzymes associated with liver function, depression, anorexia, and the appearance of macular rashes (Table 3 ). doi = 10.1371/journal.ppat.1000225 id = cord-002423-1u44tdrj author = Geoghegan, Jemma L. title = Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families date = 2017-02-08 keywords = Fig; RNA; host; virus summary = While this method does not explicitly model host-switching events, it does provide a simple means to compare multiple topologies of virus-host pairs, and accounts for differences in sample size and the fact that several viruses from a specific family can infect a single host species. Across the data set as a whole we found that all virus families displayed relatively large tree topological distances with nPH85 values of !0.6, suggesting that cross-species transmission is widespread, at least at the family-level (Fig 2; S3 Table) . As with the analysis of topological distances, this revealed that cross-species transmission was the most common evolutionary event in all virus families studied here, with co-divergence consistently less frequent (with the possible exception of the Hepadnaviridae-see below), and lineage duplication and extinction playing a much more minor role. To investigate the comparative prevalence of cross-species transmission among viruses we measured the congruence between virus and host phylogenetic trees using a normalized tree topological distance-based approach (nPH85, [14] ). doi = 10.1371/journal.ppat.1006215 id = cord-325825-0lyt8gfq author = Griffiths, Samantha J. title = A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication date = 2013-08-08 keywords = IFN; Med23; Mediator; cell; figure; hsv-1; protein; virus summary = Host factors (HFs) which positively or negatively regulate HSV-1 replication were identified by screening a druggable genome siRNA library (4 siRNAs per gene) targeting 7,237 human genes against a HSV-1 reporter virus expressing the enhanced green fluorescent protein (eGFP; HSV-1 strain C12) in the epithelial Hela cell line, due to their ease of transfection and susceptibility to HSV-1 infection [34] . Combined bioinformatic analyses of protein interaction and siRNA depletion screens found a significant functional enrichment for proteins involved in transcription, and identified multi-protein complexes enriched for pro-viral HFs which strongly inhibited HSV-1 upon depletion, including the RNA-polymerase II, eIF3 and Mediator complexes ( Figure 3a) . Furthermore, qPCR analysis found depletion of Med23 inhibited the induction of IFN-l expression following HSV-1 infection of A549 cells in comparison to cells transfected with the RSCF siRNA control ( Figure 4e ). doi = 10.1371/journal.ppat.1003514 id = cord-304815-3datxv8j author = Gronvall, Gigi Kwik title = The Scientific Response to a Pandemic date = 2006-02-24 keywords = SARS; laboratory summary = More than 150 scientists and public health practitioners from 25 countries gathered in Lyon, France, to hear speakers from the WHO, the European Commission, scientific journals, Interpol, and public health networks-many of the institutions and individuals who will likely play key roles in the global response to the next pandemic. By discussing the biosafety and biosecurity challenges presented by past epidemics such as SARS, participants recognized the importance of scientific and public health collaboration in combating disease-and the need to plan. Researchers will need to share biological samples between laboratories, sometimes internationally; decision makers and journalists will want the latest information, which may not be peer reviewed; and researchers will risk contracting the disease they research, which could then spread outside of the laboratory. Scientists need access to samples from patients and laboratories in order to conduct research and public health surveillance, as well as to develop diagnostic tests. doi = 10.1371/journal.ppat.0020009 id = cord-002706-m3y35ozx author = Guo, Fang title = HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways date = 2017-09-25 keywords = Fig; HBV; Hepatitis; dna; nucleocapsid summary = doi = 10.1371/journal.ppat.1006658 id = cord-003169-bdw5ke4i author = Guo, Hongbo title = Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces date = 2018-08-13 keywords = Fig; IAV; PR8; WSN summary = doi = 10.1371/journal.ppat.1007233 id = cord-013481-3zwq67do author = Guo, Kejun title = Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis date = 2020-10-16 keywords = CD4; Fig; HIV-1; IFN; PWH summary = doi = 10.1371/journal.ppat.1008986 id = cord-001769-2sdg5ll7 author = Guo, Sheng title = The NLRP3 Inflammasome and IL-1β Accelerate Immunologically Mediated Pathology in Experimental Viral Fulminant Hepatitis date = 2015-09-14 keywords = FGL2; Fig; MHV-3; NLRP3; ROS summary = doi = 10.1371/journal.ppat.1005155 id = cord-271692-60nlid3c author = Guo, Wen-Ping title = Phylogeny and Origins of Hantaviruses Harbored by Bats, Insectivores, and Rodents date = 2013-02-07 keywords = China; figure; virus summary = doi = 10.1371/journal.ppat.1003159 id = cord-288231-vg8bwed9 author = Haagmans, Bart L. title = The Application of Genomics to Emerging Zoonotic Viral Diseases date = 2009-10-26 keywords = SARS; host; virus summary = doi = 10.1371/journal.ppat.1000557 id = cord-289879-fh7ic0kp author = Hatesuer, Bastian title = Tmprss2 Is Essential for Influenza H1N1 Virus Pathogenesis in Mice date = 2013-12-05 keywords = H1N1; Tmprss2 summary = doi = 10.1371/journal.ppat.1003774 id = cord-286137-4cbh3u3z author = Honce, Rebekah title = They are what you eat: Shaping of viral populations through nutrition and consequences for virulence date = 2020-08-13 keywords = viral; virus summary = doi = 10.1371/journal.ppat.1008711 id = cord-355610-7xy4s483 author = Hu, Dan title = A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III date = 2019-06-26 keywords = DENV; DIII; Fig; antibody; m366.6 summary = Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate. Its fully human origin, the germline-like nature, combined with high-affinity and broad neutralizing activity toward all DENV serotypes, suggest that m366.6 is a promising candidate antiviral agent and may also provide a unique template for designing effective dengue vaccine immunogens. Two antibodies, designated as m360 and m366, bound potently to DENV DIIIs. Their scFv gene were fused with human IgG1 Fc for protein expression, and surface plasmon resonance (SPR) experiments were used to evaluate the antigens binding. doi = 10.1371/journal.ppat.1007836 id = cord-342419-liaihahj author = Huang, Jiachen title = Antibody recognition of the Pneumovirus fusion protein trimer interface date = 2020-10-09 keywords = MPV458; MPV465; RSV; hmpv summary = doi = 10.1371/journal.ppat.1008942 id = cord-332205-ydijp66b author = Hufsky, Franziska title = Virologists—Heroes need weapons date = 2018-02-08 keywords = virologist; virus summary = Nowadays, nearly everyone in the life sciences has used BLAST [8] at least once, or made an alignment, or asked a bioinformatician to analyze high-throughput sequencing data. Bioinformaticians routinely have to develop tailored, study-specific algorithms and tools used by a wide variety of scientists, including biochemists, biologists, geneticists, and molecular life scientists; but we rarely find virus-specific tools used by virologists. But astonishingly, we now know that the human genome consists of 8%-60% virus-derived sequences (depending on how this is measured: 8% can be directly traced back to viruses, whereas a figure of 60% includes LINEs and SINEs that are thought to be of viral origin [12] ). The EVBC aims to develop bioinformatical tools for nearly all areas: (1) for detection of viruses, e.g., from high-throughput sequencing data; (2) virus assembly; (3) quasispecies reconstruction; (4) intraviral interactions; (5) virus entry, i.e., protein-protein interaction; (6) virus -host interactions; (7) phylogeny/cophylogeny; and (8) therapy. doi = 10.1371/journal.ppat.1006771 id = cord-325624-6anybxnk author = Ireland, Derek D. C. title = RNase L Mediated Protection from Virus Induced Demyelination date = 2009-10-02 keywords = CNS; IFN; MHV; RNA summary = The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. RNase L specifically protected the brain stem from sustained infection and prevented spread of virus to microglia/macrophages located in spinal cord grey matter. The increased pathological changes in both brain stem and spinal cord thus correlated with the high mortality rates of RL 2/2 mice starting at day 9 p.i. The inability to directly link increased axonal damage with enhanced neuronal infection remains puzzling and supports dysregulation of oligodendrocyte function and/or neuroprotective functions of microglia as contributing factors to the severe pathological phenotype and clinical outcome. Numerous functions of RNase L, not directly associated with anti-viral activity, may contribute to the increased susceptibility of RL 2/2 mice to MHV-JHM infection. doi = 10.1371/journal.ppat.1000602 id = cord-333473-c1lykari author = Irigoyen, Nerea title = High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling date = 2016-02-26 keywords = A59; AUG; CHX; Fig; MHV; ORF; RNA; UTR summary = Also, it has been employed in the study of the replication of large DNA viruses; namely, human cytomegalovirus [17] [18] , Kaposi''s sarcoma-associated herpesvirus [19] , herpes simplex virus 1 [20] , vaccinia virus [21] , and bacteriophage lambda [22] , providing insights into the temporal regulation of gene expression in these viruses and identifying numerous previously unrecognized translated ORFs, including novel protein-coding ORFs and short regulatory uORFs. In this paper, we describe the first analysis of RNA virus replication and gene expression by ribosome profiling (and parallel RNASeq), using MHV as a model system. The latter are calculated on a per gene (rather than per transcript) basis, using RNASeq and RiboSeq reads contained entirely within annotated CDS regions (i.e. excluding 5 0 and 3 0 UTRs and also RPFs accumulating at or near to initiation or termination sites), and, like the virus values, are expressed relative to the mean levels for the cell (due to normalization by library size). doi = 10.1371/journal.ppat.1005473 id = cord-002542-f7l4ty2j author = Jaworski, Elizabeth title = Parallel ClickSeq and Nanopore sequencing elucidates the rapid evolution of defective-interfering RNAs in Flock House virus date = 2017-05-05 keywords = FHV; Fig; RNA; RNA1; RNA2 summary = Using a combination of longand short-read Next-Generation Sequencing, we have characterized the formation of DI-RNAs during serial passaging of Flock House virus (FHV) in cell-culture over a period of 30 days in order to elucidate the pathways and potential mechanisms of DI-RNA emergence and evolution. By combining these data, we aimed to determine the correlation of recombination events within single RNA virus genomes, characterize the distribution of defective RNA genomes, and determine the exact make-up of DI-RNAs during serial passaging of FHV in cell culture. This observation indicates the protection of cells from infection and/or CPE when supplied with a large dose of viral particles that contain a large proportion of DI-RNAs. In this manuscript, we sought to provide a thorough and comprehensive analysis of the frequency and identity of recombination events present during the serial passaging of Flock House virus in cell culture in order to elucidate the pathways and mechanism of DI-RNA emergence and evolution. doi = 10.1371/journal.ppat.1006365 id = cord-253783-3a1qde41 author = Johnson, Christopher J title = Prions Adhere to Soil Minerals and Remain Infectious date = 2006-04-14 keywords = Mte; TSE; prp summary = We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc)) with common soil minerals. X-ray diffraction analysis provided no evidence that PrP Sc entered Mte interlayer spaces (Mte d 001 spacings were 1.22 nm and 1.47 nm before and after PrP Sc adsorption, respectively); prion protein appeared to adsorb to only external clay surfaces. Prion protein desorbed from Kte and quartz did not exhibit a change in molecular mass ( Figure 1A ), suggesting that surface properties specific to Mte were responsible for the cleavage. To control for any unbound prion protein that may have cosedimented with Mte particles, mineral-free PrP Sc suspensions were processed in the same manner as in sorption experiments. Our results demonstrate that all soil mineral surfaces examined bound PrP Sc and that Mte and quartz have larger specific binding capacities for PrP Sc than does Kte (Figure 1 ). doi = 10.1371/journal.ppat.0020032 id = cord-351548-jvl63652 author = Juranic Lisnic, Vanda title = Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface date = 2013-09-26 keywords = MAT; MCMV; RNA; Seq; figure; gene; transcript summary = Finally, a recent transcriptomic analysis of newly synthesized RNA in MCMV infected fibroblasts [15] applied RNA-Seq technology to study regulation of viral gene expression and identified a very early peak of viral gene transcriptional activity at 1-2 hours post infection followed by rapid cellular countermeasures but did not attempt to re-annotate MCMV genome. The MCMV transcripts identified through our classical cDNA cloning and sequencing (green arrows) and the RNA-Seq expression profiles (gray histograms), showed complementary results to each other but diverged dramatically from current annotations. Because cDNA cloning and RNA-Seq identified significant differences between the MCMV transcriptome and current annotations, we performed an in depth analysis of several genomic regions by northern analyses ( Figure 5 , Figures S2, S3 , S4, S5) using our cDNA clones to generate strand specific riboprobes ( Table 1) . doi = 10.1371/journal.ppat.1003611 id = cord-278569-yr06jwm1 author = Karnam, Guruswamy title = CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection date = 2012-05-17 keywords = IFN; TLR7; cd200; figure summary = doi = 10.1371/journal.ppat.1002710 id = cord-342825-s8ddek2f author = Kim, Ye Ji title = Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators date = 2016-08-26 keywords = Fig; HCMV; Herc5; UL26; ie1; isg15 summary = RNA interference of UBE1L (E1), UbcH8 (E2), Herc5 (E3), and UBP43 (ISG15 protease) revealed that ISGylation inhibits HCMV growth by downregulating viral gene expression and virion release in a manner that is more prominent at low multiplicity of infection. This result suggests that an indirect effect of virus infection on neighboring uninfected cells is responsible for the greater induction of ISG15 and protein ISGylation by HCMV than by UV-HCMV at low MOIs. Since HCMV IE1 inhibits the activation of ISRE-containing promoters by sequestering STAT2 [58] [59] [60] and PML [61] , IE1 expression may be responsible for the suppression of free ISG15 and ISG15 conjugate levels during HCMV infection. In addition to IE1, the presence of additional viral functions that downregulate protein ISGylation was prompted by our observation that UV-HCMV infection resulted in a higher level of ISG15 conjugates than IE1-deleted mutant virus at late times (Fig 2B) . doi = 10.1371/journal.ppat.1005850 id = cord-280621-tph5n7ak author = Kim, Yunjeong title = Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor date = 2016-03-30 keywords = FIPV; Fig; GC376; SARS; npi64 summary = Shifts in tissue or cell tropism and resulting changes in virulence have also been reported for coronaviruses; porcine respiratory coronavirus causes mild respiratory infection in pigs and presumably arose from transmissible gastroenteritis virus (TGEV), the etiologic agent of gastroenteritis in young pigs with a high fatality, by spontaneous mutations and/or deletions in its genome [9] . Effective treatment intervention for coronavirus infections with an immunopathological component, such as SARS, MERS and FIP, is speculated to involve the judicious use of immunomodulatory agents to enhance protective host immunity and decrease pathological immune responses and antiviral drugs to directly inhibit viral replication. These results on viral titers show that FIPV 3CLpro is a valid target for FIPV antiviral drugs and GC376 can effectively reduce the virus load in the macrophages from the ascites and the omentum of cats with FIP. doi = 10.1371/journal.ppat.1005531 id = cord-343221-e29of29o author = Kindler, Eveline title = Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication date = 2017-02-03 keywords = A59; Fig; H277A; IFN; MHV; RNA summary = Specifically, we show that genetically engineered mutants of mouse hepatitis virus (MHV) and human coronavirus 229E (HCoV-229E), respectively, that encode an EndoU active-site substitution known to abolish nucleolytic activity, were severely attenuated and elicited an immediate and simultaneous activation of host cell dsRNA sensors. The severe attenuation of MHV H277A and HCoV-229E H250A replication in wild-type murine and human macrophages, respectively, precluded the use of primary macrophages to assess the sensitivity of EndoU-deficient coronaviruses to IFN-I pre-treatment. Our data suggest that direct restriction of replication of EndoU-deficient coronaviruses is mediated by RNase L-mediated RNA degradation and inhibition of host cell translation through activation of PKR. Notably, also in this case Xrn1 is required to further process the de-capped mRNAs. Our data show that early during coronavirus infection the EndoU activity conceptually fulfils the same task, namely the removal of dsRNA that would otherwise trigger host cell dsRNA responses, such as IFN-β expression and activation of PKR and OAS/RNase L. doi = 10.1371/journal.ppat.1006195 id = cord-004428-ob5igsv5 author = Kizziah, James L. title = Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage date = 2020-02-18 keywords = Dit; Fig; MTP; RBP; Tal summary = Crystal structures have also been determined for Bacillus phage SPP1 Dit [25] and the baseplates of lactococcal phages p2 and TP901-1, which include Dit, Tal, BppU, and receptor binding proteins that are not similar to the ϕ11 RBP [23, 26] . Atomic models for MTP (gp53), Dit (gp58), RBP (gp61), and parts of Tal (gp59), FibL (gp62), FibU (gp68) and TMP (gp57) were built into either the C6 or C3 baseplate reconstructions, using I-TASSER models as starting points [29] , complemented with real-space refinement in PHENIX [30] . RBP is a trimeric protein consisting of four domains: an N-terminal α-helical coiled-coil "stem" domain (residues 1-142) that is folded by 155˚at a central hinge; a fivebladed β-propeller "platform" domain (residues 143-442) that was previously suggested to bind to the GlcNAc residues of WTA on the host cell surface [21, 24] ; and two highly similar C-terminal "tower" domains (residues 443-636; S1 Table) , each consisting of a bent β-sheet superposed by an α-helix (Fig 5A) . doi = 10.1371/journal.ppat.1008314 id = cord-000578-jhetyd9t author = Kovalev, Nikolay title = A Co-Opted DEAD-Box RNA Helicase Enhances Tombusvirus Plus-Strand Synthesis date = 2012-02-16 keywords = CFE; FHV; RNA; TBSV; figure summary = doi = 10.1371/journal.ppat.1002537 id = cord-001257-t21l6i3f author = Kovalev, Nikolay title = The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication date = 2014-04-17 keywords = Fig; REN; RIII(2; RNA; TBSV summary = Novel pro-viral function of AtRH2, AtRH5 and the yeast Dbp3p and Fal1p is to bind to the viral replication enhancer present in the tombusvirus minus-strand RNA To test if AtRH2, AtRH5 and the yeast Dbp3p and Fal1p play a comparable role with the previously analyzed yeast Ded1p (human DDX3-like) and Dbp2p (human p68-like) and the ortologous AtRH20 DEAD-box helicases [30, 49] , first we performed in vitro RNA binding experiments with affinity-purified recombinant helicase proteins. The replication process leads to the production of abundant (+)RNA progeny, while the (2)RNA templates are likely sequestered in dsRNA forms within the VRCs. The presented in vitro data based on the solubilized/purified tombusvirus replicase and the CFE assay containing the membrane-bound VRC indicate that the eIF4AIIIlike RNA helicases can mainly stimulate TBSV (+)-strand synthesis, while their effects on (2)RNA synthesis have not been observed (not shown). doi = 10.1371/journal.ppat.1004051 id = cord-000933-nn9gj0z1 author = Krzyzaniak, Magdalena Anna title = Host Cell Entry of Respiratory Syncytial Virus Involves Macropinocytosis Followed by Proteolytic Activation of the F Protein date = 2013-04-11 keywords = FACS; Fig; GFP; RSV; Rab5; cell; virus summary = To study the entry process in human tissue culture cells (HeLa, A549), we used fluorescence microscopy and developed quantitative, FACS-based assays to follow virus binding to cells, endocytosis, intracellular trafficking, membrane fusion, and infection. To determine the pathway of RSV entry into HeLa and A549 cells, we developed quantitative fluorescence-activated cell sorting (FACS) assays and complemented them with confocal microscopy to monitor cell binding of RSV, endocytosis, fusion, and infection. Since we did not detect free capsids that would stain only for N or P (data not shown), we used the presence of the capsid antigens to distinguish between intact RSVs and VLPs. When purified virus preparations were incubated with HeLa cells at 4uC, immunoblotting after SDS-PAGE showed that more than half of the input N and P associated with the cells indicating that RSV binding in the cold was efficient (Fig. 1C) . doi = 10.1371/journal.ppat.1003309 id = cord-013526-6fip93l2 author = Labadie, Thomas title = A non-enveloped arbovirus released in lysosome-derived extracellular vesicles induces super-infection exclusion date = 2020-10-19 keywords = BTV; Fig; PBS; cell; virus summary = doi = 10.1371/journal.ppat.1009015 id = cord-076082-4kpkhz0o author = Lam, Tommy Tsan-Yuk title = Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia date = 2008-08-22 keywords = H5N1; Indonesia; Java; figure; virus summary = doi = 10.1371/journal.ppat.1000130 id = cord-000318-wk2u2a9w author = Lamb, Daniel title = Charge-Surrounded Pockets and Electrostatic Interactions with Small Ions Modulate the Activity of Retroviral Fusion Proteins date = 2011-02-03 keywords = BLV; Fig; HTLV-1; LHR summary = Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry. The BLV crystal structure and our analysis of HTLV-1 and BLV envelope-mediated membrane fusion reveal an important role for electrostatic interactions in binding of the LHR to the grooves of the coiled coil. doi = 10.1371/journal.ppat.1001268 id = cord-353353-njvalb44 author = Lau, Susanna K. P. title = Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model date = 2016-10-13 keywords = PCR; RASM14A; Rosavirus summary = Analysis of 13 complete genome sequences showed that "Rosavirus B" and "Rosavirus C" represent two potentially novel picornavirus species infecting different rodents. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Rosavirus C isolated from cell culture causes multisystemic diseases in a mouse model, with histopathological changes and positive viral antigen expression in lungs and liver of infected mice. A total of 13 complete genomes from samples of four different wild rodent species (chestnut spiny rat, Coxing''s white-bellied rat, roof rat and Indochinese forest rat) positive for "Rosavirus C" and one street rodent species (Norway rat) positive for "Rosavirus B" were sequenced directly from the positive respiratory or alimentary samples and characterized. Infected cell lines and tissues from challenged mice that were tested positive for rosavirus C RASM14A by RT-PCR were subject to viral load studies and immunohistochemical staining for viral VP1 protein as described previously [28, 69] . doi = 10.1371/journal.ppat.1005911 id = cord-324928-cpryxa6p author = Lello, Laura Sandra title = Cross-utilisation of template RNAs by alphavirus replicases date = 2020-09-04 keywords = CHIKV; Fig; RNA; SFV; SINV summary = The differences between outgroup viruses and those belonging to the SFV complex had an impact on the design of the template RNAs. The 5'' region of the CHIKV genome contains seven SL structures that affect genome replication in mammalian and/or mosquito cells [33] . Cross-utilisation of template RNAs by alphavirus replicases structures can be predicted for RNAs of other members of the SFV complex (S1 Fig), the 5'' ends of the template RNAs of SFV, MAYV, RRV and ONNV had an identical design to that of the previously constructed CHIKV template, i.e. the 5'' UTR was followed by 231nt encoding the N-terminus of nsP1 [43] . The levels of Fluc and Gluc expression in human cells, transfected with plasmids expressing template RNA and corresponding polymerase negative control replicase (P1234 GAA ), were similar for trans-replicases derived from different viruses and the same was observed for Ae albopictus cells. doi = 10.1371/journal.ppat.1008825 id = cord-002530-ao7kenbx author = Lin, Yao-Tang title = The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication date = 2017-05-11 keywords = HCMV; MIE; VCP; ie1; ie2 summary = doi = 10.1371/journal.ppat.1006329 id = cord-294342-7ycgd0h7 author = Markosyan, Ruben M. title = Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger date = 2016-01-05 keywords = EBOV; Fig; NPC1; cell summary = doi = 10.1371/journal.ppat.1005373 id = cord-000729-iq30z094 author = Marsh, Glenn A. title = Cedar Virus: A Novel Henipavirus Isolated from Australian Bats date = 2012-08-02 keywords = CedPV; Fig; Nipah; RNA; virus summary = The genome size (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and it uses the same receptor molecule (ephrinB2) for entry during infection. Preliminary challenge studies with CedPV in ferrets and guinea pigs, both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralizing antibodies although clinical disease was not observed. As part of our on-going field studies on HeV genetic diversity and infection dynamics in the Queensland flying fox populations, urine samples were collected on a regular basis for PCR and virus isolation. CedPV is more closely related to HeV and NiV than henipavirus-like sequences detected in African bats [26, 32] as shown in a phylogenetic tree based on the only sequences available of a 550-nt L gene fragment (Fig. S5) . doi = 10.1371/journal.ppat.1002836 id = cord-266078-h53zpjab author = McGuckin Wuertz, Kathryn title = STING is required for host defense against neuropathological West Nile virus infection date = 2019-08-15 keywords = CNS; Fig; Nile; WNV; West; sting summary = Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. In vivo, STING-/mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. In the CNS however, we observed a trend toward increased viral RNA and innate immune gene expression at 8 dpi in WNV-infected STING-/-mice, similar to that observed in BMDM (Fig 3A and 3D) . These observations suggest that STING plays a role in directing or maintaining the T cell response to specific loci within the CNS or that initial viral infection led to increased STING is required for host defense against neuropathological West Nile virus infection recruitment of a localized adaptive immune response that resulted in immunopathology. doi = 10.1371/journal.ppat.1007899 id = cord-002893-d7hetoq0 author = Meng, Xiangzhi title = A paralogous pair of mammalian host restriction factors form a critical host barrier against poxvirus infection date = 2018-02-15 keywords = Fig; SAMD9L; VACV summary = Human SAMD9, a tumor suppressor and a restriction factor for poxviruses in cell lines, is antagonized by two classes of poxvirus proteins, represented by vaccinia virus (VACV) K1 and C7. Both paralogs are antagonized by VACV K1, C7 and C7 homologs from diverse mammalian poxviruses, but mouse SAMD9L is resistant to the C7 homolog encoded by a group of poxviruses with a narrow host range in ruminants, indicating that host species-specific difference in SAMD9/SAMD9L genes serves as a barrier for cross-species poxvirus transmission. VACV K1, C7 and C7 homologs from diverse poxviruses could overcome hSAMD9L restriction, but the sheeppox virus C7 homolog has reduced potency due to the variation of two residues To find out whether mammalian poxviruses could overcome the restriction of hSAMD9L, we induced hSAMD9L expression in ΔhSAMD9 HeLa cells with 200 U/ml of IFN-β and then infected the cells with our panel of vK1L -C7L --derived VACVs. Viruses that expressed VACV-K1, VACV-C7, MYXV-M62, SPPV-063, SWPV-064 and YLDV-67 (but not MYXV-M63 and MYXV-M64) grew in IFN-treated ΔhSAMD9 cells (Fig 5A) , indicating that all known SAMD9 antagonists could also antagonize hSAMD9L. doi = 10.1371/journal.ppat.1006884 id = cord-350640-sz6xj5o3 author = Menzel, Nicolas title = MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles date = 2012-07-26 keywords = HCV; Py-2; RNA; figure; pla2g4a summary = doi = 10.1371/journal.ppat.1002829 id = cord-332747-u46xryoo author = Mingorance, Lidia title = Host phosphatidic acid phosphatase lipin1 is rate limiting for functional hepatitis C virus replicase complex formation date = 2018-09-18 keywords = Fig; HCV; LPIN1; RNA; cell; infection; ns3 summary = doi = 10.1371/journal.ppat.1007284 id = cord-280221-s6oxq772 author = Montelongo-Jauregui, Daniel title = Convalescent serum therapy for COVID-19: A 19th century remedy for a 21st century disease date = 2020-08-12 keywords = COVID-19; plasma summary = doi = 10.1371/journal.ppat.1008735 id = cord-334315-ymkrgj0h author = Moon, Stephanie L. title = Cytoplasmic Viruses: Rage against the (Cellular RNA Decay) Machine date = 2013-12-05 keywords = RNA; decay summary = This review describes the myriad ways that viruses deal with the general host RNA decay machinery that is active in the cell immediately upon viral infection-turning what, at first, appears to be very hostile territory for a foreign transcript into a sort of ''''promised land'''' for viral gene expression. Disparate RNA viruses have, therefore, evolved unique mechanisms by which they disarm host RNA decay pathways by inactivating or proteolytically degrading important nucleases to promote productive viral infections. In addition, to make a cell more amenable to virus production, these virally encoded nucleases may also create a new ''''sandbox'''' in the cytoplasm for viral RNAs by initiating the large-scale decay of cellular mRNAs and dramatically altering the landscape of host gene expression. Considering the importance of RNA stability in regulating transcript abundance, the inactivation or commandeering of cellular RNA decay factors by viruses is likely to significantly alter host gene expression. doi = 10.1371/journal.ppat.1003762 id = cord-310509-c8wp2m69 author = Morens, David M. title = Emerging Infectious Diseases: Threats to Human Health and Global Stability date = 2013-07-04 keywords = disease; human summary = doi = 10.1371/journal.ppat.1003467 id = cord-346053-mk1mzc5z author = Morris, Cindy E. title = Expanding the Paradigms of Plant Pathogen Life History and Evolution of Parasitic Fitness beyond Agricultural Boundaries date = 2009-12-24 keywords = evolution; factor; pathogen; plant; virulence summary = We present numerous examples of virulence traits in plant pathogenic microorganisms that also have a function in their survival and growth in nonagricultural and nonplant habitats. Adaptation to biotic and abiotic stresses, within or outside of agricultural habitats, likely plays as important a role in the evolution of parasitic fitness of plant pathogens as it does for human pathogens. As illustrated above, traits that confer fitness in response to biotic and abiotic environmental stress can have dual-use as virulence factors in human pathogens. In plant pathogens, the transport systems for toxins and antimicrobials can have broad spectrum activity, leading to resistance to agricultural fungicides and also contributing to virulence [12] . The examples listed above that describe traits that play roles in both environmental fitness and virulence to plants provide a compelling incentive to expand our paradigms concerning the forces that drive evolution of plant pathogenicity. doi = 10.1371/journal.ppat.1000693 id = cord-341034-2oigu75k author = Moser, Theresa S. title = AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis date = 2012-04-19 keywords = ACC; AMPK; LKB1; RNA; RVFV; figure summary = doi = 10.1371/journal.ppat.1002661 id = cord-262753-jld1ygxt author = Neidermyer, William J. title = Global analysis of polysome-associated mRNA in vesicular stomatitis virus infected cells date = 2019-06-21 keywords = Fig; RNA; VSV; cell; polysome; viral summary = doi = 10.1371/journal.ppat.1007875 id = cord-000018-amvlm09p author = Pauli, Eva-K. title = Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression date = 2008-11-07 keywords = IFN; RNA; SOCS-3; figure; stat1 summary = Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNα/β, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1) was strongly reduced. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. These results are consistent with data gained from previous experiments in Vero cells ( Figure 1E ) and indicate that neither induction of SOCS-3 mRNA nor inhibition of STAT phosphorylation is dependent on virus-induced type I IFN expression. To answer the question whether enhanced STAT phosphorylation in SOCS-3 deficient cells would also lead to enhanced expression of ISGs, total RNA was isolated at different time points p.i. from infected wild type and knock out cells and monitored for induction of SP110, IRF-1 and OAS1 ( Figure 7E, 7F and 7G ). doi = 10.1371/journal.ppat.1000196 id = cord-351952-lhhjax3s author = Pickering, Suzanne title = Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings date = 2020-09-24 keywords = ELISA; Fig; SARS summary = doi = 10.1371/journal.ppat.1008817 id = cord-290617-45be6gxe author = Poulain, Florian title = Footprint of the host restriction factors APOBEC3 on the genome of human viruses date = 2020-08-14 keywords = Fig; NTC; dna; virus summary = Certain viruses actively encode viral proteins antagonizing the APOBEC3s, others passively face the APOBEC3 selection pressure thanks to a depleted genome for APOBEC3-targeted motifs. By breaking down the human viruses into their respective Baltimore''s group (S3 Fig), we observed that NTC depletion is not present in reverse transcribing nor in negative sense single strand RNA viruses. We also observed a mild general NCC depletion in single strand DNA and double strand RNA viruses, justifying further investigation for a possible A3G-induced footprint (S1 Fig). In order to identify A3-footprinted viruses, we detailed the NTC and NNGANN ratios for 870 human viral species (Fig 4A) . B. The observed/expected ratios of TC dinucleotide at various codon positions and on both strands (i.e. NNTCNN, TCN, NTC, GAN, NGA and NNGANN) were calculated for the putative A3-footprinted viral species and depicted by a heatmap. doi = 10.1371/journal.ppat.1008718 id = cord-303403-9th2jiq6 author = Qing, Jie title = Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator date = 2014-10-02 keywords = CypA; EV71; Fig; RNA; VP1 summary = doi = 10.1371/journal.ppat.1004422 id = cord-254735-8reu45yz author = Reguera, Juan title = Structural Bases of Coronavirus Attachment to Host Aminopeptidase N and Its Inhibition by Neutralizing Antibodies date = 2012-08-02 keywords = APN; PRCV; RBD; TGEV; figure summary = doi = 10.1371/journal.ppat.1002859 id = cord-002142-tdgu9sr9 author = Reniere, Michelle L. title = An In Vivo Selection Identifies Listeria monocytogenes Genes Required to Sense the Intracellular Environment and Activate Virulence Factor Expression date = 2016-07-14 keywords = Fig; Listeria; Spx; gene summary = doi = 10.1371/journal.ppat.1005741 id = cord-001385-rb5vwolt author = Reuven, Eliran Moshe title = The HIV-1 Envelope Transmembrane Domain Binds TLR2 through a Distinct Dimerization Motif and Inhibits TLR2-Mediated Responses date = 2014-08-14 keywords = ENV; HIV-1; TLR2; TMD; figure summary = doi = 10.1371/journal.ppat.1004248 id = cord-314451-mqnqjn0c author = Roberts, Anjeanette title = A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice date = 2007-01-12 keywords = BALB; CoV; MA15; SARS; TCID; Urbani summary = To generate a model that satisfies these criteria, we have serially passaged SARS-CoV in the respiratory tract of young BALB/c mice, resulting in a lethal virus that causes dosedependent weight loss and mortality associated with higher viral titers in the respiratory tract than are seen with the wildtype virus and with histopathologic findings of severe pulmonary disease. Northern blot analysis of RNA from infected Vero E6 cells indicated that genomic vRNA and viral mRNA and all eight sub-genomic mRNAs were present in similar ratios for the recombinant viruses and MA15 virus as for SARS-CoV (Urbani) ( Figure 2A ). In order to evaluate whether changes in tissue tropism or levels of viral replication could contribute to the lethal phenotype of the MA15 virus, viral titers in lungs, spleen, liver, and brain of BALB/c mice were determined at various time points following intranasal inoculation with SARS-CoV (Urbani) or MA15. doi = 10.1371/journal.ppat.0030005 id = cord-290253-hxxizipk author = Roberts, Katherine E. title = Changes in temperature alter the potential outcomes of virus host shifts date = 2018-10-19 keywords = Drosophila; host; specie; temperature summary = doi = 10.1371/journal.ppat.1007185 id = cord-334947-pa0p5dif author = Rozen-Gagnon, Kathryn title = Alphavirus Mutator Variants Present Host-Specific Defects and Attenuation in Mammalian and Insect Models date = 2014-01-16 keywords = CHIKV; RNA; SINV; cell; figure; virus summary = Since residue 483 is conserved among alphaviruses, we examined the analogous mutations in Sindbis virus (SINV), which also reduced polymerase fidelity and generated replication defects in mosquito cells. To estimate the population diversity of variants by deep sequencing, cDNA libraries were prepared by Superscript III from RNA extracted from virus generated in BHK-21 or C6/36 cells, and the viral genome was amplified using a high fidelity polymerase (Phusion) to generate 5 overlapping amplicons 2-3 kb in length. To address the possibility that the fitness cost of defective replication, observed in mosquito cell culture, would favor the reversion of these mutant polymerases to wildtype, we deep sequenced virus from the body of an individual mosquito that presented the median titer from each group. doi = 10.1371/journal.ppat.1003877 id = cord-286072-kgpvdb42 author = Sa Ribero, Margarida title = Interplay between SARS-CoV-2 and the type I interferon response date = 2020-07-29 keywords = IFN; MERS; SARS; cell; response summary = doi = 10.1371/journal.ppat.1008737 id = cord-356115-vblgotjn author = Sawicki, Stanley G title = Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase Proteins date = 2005-12-09 keywords = A59; Alb; MHV; RNA summary = doi = 10.1371/journal.ppat.0010039 id = cord-355839-o0m71kvw author = Sedeyn, Koen title = Respiratory syncytial virus nonstructural proteins 1 and 2: Exceptional disrupters of innate immune responses date = 2019-10-17 keywords = IFN; NS2; RSV; ns1; rig summary = ATF2, activating transcription factor 2; CDS, cytoplasmic DNA sensor; ER, endoplasmic reticulum; IFN, interferon; IKK, inhibitor of nuclear factor kappa-B kinase; IKKε, inhibitor of nuclear factor kappa-B kinase subunit epsilon; IRF3, interferon regulatory factor 3; IRF7, interferon regulatory factor 7; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MAVS, mitochondrial antiviral-signaling protein; MDA5, melanoma differentiation-associated protein 5; MyD88, myeloid differentiation primary response protein MyD88; NF-kB, nuclear factor-kappa B; NOD2, nucleotide-binding oligomerization domain-containing protein 2; PAMP, pathogenassociated molecular pattern; PRR, pattern recognition receptor; RIG, retinoic-acid-inducible gene-I; RLR, RIG-I-like receptor; RSV, respiratory syncytial virus; STING, stimulator of interferon protein; TBK1, tank binding kinase 1; TICAM1, toll/interleukin-1 receptor domain-containing adapter molecule 1; TIRAP, toll/ interleukin-1 receptor domain-containing adapter protein; TLR, toll-like receptor; TRAF3, tumor necrosis factor receptor-associated factor 3; TRAF6, tumor necrosis factor receptor-associated factor 6; TRAM, toll-like receptor adaptor molecule. doi = 10.1371/journal.ppat.1007984 id = cord-316584-b1aa1lri author = Seiradake, Elena title = The Cell Adhesion Molecule “CAR” and Sialic Acid on Human Erythrocytes Influence Adenovirus In Vivo Biodistribution date = 2009-01-02 keywords = CAV-2; car; erythrocyte; fiber; figure; head summary = doi = 10.1371/journal.ppat.1000277 id = cord-292424-daj4zcm1 author = Shang, Jian title = Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry date = 2020-03-09 keywords = Fig; MHV summary = doi = 10.1371/journal.ppat.1008392 id = cord-323568-s0wmll4q author = Shang, Jian title = Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins date = 2018-04-23 keywords = Fig; IBV; S1-CTD summary = doi = 10.1371/journal.ppat.1007009 id = cord-268388-kkhuzf3p author = Sharif-Yakan, Ahmad title = Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives date = 2014-12-04 keywords = CoV; MERS; respiratory summary = Two years have passed since the initial description of the Middle East respiratory syndrome coronavirus (MERS-CoV), yet the epidemic is far from being controlled. First reported in 2012 [1] , Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus and the first lineage 2C Betacoronavirus known to infect humans [2] . Middle east respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, qatar Middle east respiratory syndrome coronavirus (MERS-CoV) in dromedary camels Epidemiological, demographic, and clinical characteristics of 47 cases of middle east respiratory syndrome coronavirus disease from saudi arabia: A descriptive study Clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: A report of nosocomial transmission Clinical features and virological analysis of a case of middle east respiratory syndrome coronavirus infection Ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome coronavirus: An observational study doi = 10.1371/journal.ppat.1004457 id = cord-001676-68y733y3 author = Shoemaker, Jason E. title = An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation date = 2015-06-05 keywords = Fig; H5N1; IFN; pfu; virus summary = doi = 10.1371/journal.ppat.1004856 id = cord-264579-csro48ks author = Sigalov, Alexander B. title = Novel Mechanistic Insights into Viral Modulation of Immune Receptor Signaling date = 2009-07-31 keywords = TCR summary = doi = 10.1371/journal.ppat.1000404 id = cord-002608-zn7tm1ww author = Sokoloski, Kevin J. title = Identification of Interactions between Sindbis Virus Capsid Protein and Cytoplasmic vRNA as Novel Virulence Determinants date = 2017-06-29 keywords = Fig; RNA; SINV; interaction; viral summary = doi = 10.1371/journal.ppat.1006473 id = cord-001655-uqw74ra0 author = Stenglein, Mark D. title = Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections date = 2015-05-20 keywords = Fig; PCR; RNA; genotype summary = doi = 10.1371/journal.ppat.1004900 id = cord-258234-qn8xp4v9 author = Striker, Rob title = Inhibitors of Peptidyl Proline Isomerases As Antivirals in Hepatitis C and Other Viruses date = 2014-11-06 keywords = HCV; NS5A summary = Cyclophilin inhibitors that reduce viral replication also block interactions between cyclophilin A and NS5A, suggesting that this association is important during the viral life cycle and might be the relevant target of the antiviral activity of cyclosporine [11] [12] [13] . HCV NS5A is a protein that is rich in both proline residues and disorder and that associates with cyclophilin A via domain 2. However, these regions share several common properties: the flexible cyclophilin-interacting loop in CA is also bracketed by prolines, just as the PAWARPDYNP motif in HCV; residues 86, 91, and 96 that surround the glycine-proline in CA influence viral susceptibility to cyclophillin inhibitors similar to mutations surrounding NS5A P319 [25] ; and the critical glycine-proline is amino-terminal to regions of CA that are actually more proline rich and predicted by bioinformatics analysis to be disordered, analogous to the positioning of the PAWARPDYNP motif in HCV NS5A. doi = 10.1371/journal.ppat.1004428 id = cord-000164-094d0rn6 author = Suthar, Mehul S. title = IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity date = 2010-02-05 keywords = Fig; IFN; IPS-1; WNV summary = Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1(−/−) mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. To define the role of IPS-1 in controlling virus replication and innate immunity in myeloid cells, we analyzed WNV infection and host responses in primary bone marrow-derived DC and Mw recovered from wild type and IPS-1 2/2 mice. doi = 10.1371/journal.ppat.1000757 id = cord-264225-vzcfeh7t author = Talbert-Slagle, Kristina title = Cellular Superspreaders: An Epidemiological Perspective on HIV Infection inside the Body date = 2014-05-08 keywords = CD4; HIV; HIV-1 summary = doi = 10.1371/journal.ppat.1004092 id = cord-311383-1aqt65cc author = Tan, Jinzhi title = The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes date = 2009-05-15 keywords = ADP; Nsp3; SARS; SUD summary = doi = 10.1371/journal.ppat.1000428 id = cord-001109-xs7df6a7 author = Tapia, Karla title = Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity date = 2013-10-31 keywords = Cantell; Fig; IFN; RNA summary = We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. To further investigate the cellular mechanisms responsible for the efficient activation of the antiviral response by SeV DVGs, we evaluated the phosphorylation of transcription factors that are critical for the expression of type I IFNs in cells infected with equivalent amounts of infectious particles of a SeV strain Cantell stock containing high levels of copy-back DVGs (SeV Cantell HD) or with SeV Cantell depleted of DVGs (SeV Cantell LD). Based on the potent ability of SeV stocks containing a high content of copy-back DVGs to induce the host response to infection in vitro [23, 24, 25, 28] (Fig. 1 ) and on our prior reports of strong host responses to DVGs regardless of the presence of functional virus-encoded antagonists [23, 24] , we hypothesized that DVGs that arise in situ during viral infections provide essential stimuli to initiate an antiviral immune response. doi = 10.1371/journal.ppat.1003703 id = cord-002835-qaogpxy9 author = Too, Issac Horng Khit title = Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis date = 2018-01-11 keywords = EV71; Fig; NSC-34; PHB; Roc; cell; protein summary = doi = 10.1371/journal.ppat.1006778 id = cord-000246-mlhd9zbs author = Valkenburg, Sophie A. title = Protective Efficacy of Cross-Reactive CD8(+) T Cells Recognising Mutant Viral Epitopes Depends on Peptide-MHC-I Structural Interactions and T Cell Activation Threshold date = 2010-08-12 keywords = CD8; Fig; NPN3A; TCR summary = doi = 10.1371/journal.ppat.1001039 id = cord-277566-j3ehiwn9 author = Verheije, Monique H. title = Mouse Hepatitis Coronavirus RNA Replication Depends on GBF1-Mediated ARF1 Activation date = 2008-06-13 keywords = ARF1; BFA; GBF1; Golgi; MHV; RNA summary = doi = 10.1371/journal.ppat.1000088 id = cord-353337-o302vxqm author = Visser, Linda J. title = Dissecting distinct proteolytic activities of FMDV L(pro) implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression date = 2020-07-15 keywords = EMCV; FMDV; IFN; RLR; TBK1 summary = To study the effects of L pro on the induction of type I IFN in picornavirus-infected cells, we used two previously generated recombinant viruses; EMCV-L Zn , which contains inactivating mutations in the zinc-finger domain of the Leader (i.e. EMCV''s RLR signaling antagonist) [1, 43, 44] , and EMCV-L pro , which was derived from EMCV-L Zn and additionally encodes FMDV L pro at the N-terminus of its polyprotein ( Fig 1A) [45]. Cleavage of RLR signaling proteins by FMDV L pro correlates with type I IFN suppression degradation of NF-κB p65 and DUB activity as well as to impair L pro ''s ability to reduce IFN-β mRNA expression [36, 39] , also affected L pro ''s ability to cleave MAVS and TBK1. Notably, infection with EMCV L pro L143A, which displayed wt deISGylase/DUB activity but is strongly impaired in its ability to cleave/degrade RLR signaling proteins MAVS, TBK1 and NFκB p65, failed to suppress the induction of IFN-β mRNA. doi = 10.1371/journal.ppat.1008702 id = cord-001541-5d64esp4 author = Walker, Peter J. title = Evolution of Genome Size and Complexity in the Rhabdoviridae date = 2015-02-13 keywords = Fig; ORF; RNA; gene summary = We demonstrate that remarkable changes in genome size and complexity have occurred in rhabdoviruses in a clade-specific manner, primarily by extension and insertion of additional transcriptional units in the structural protein gene junctions, followed by occasional losses. All rhabdovirus genomes contained the five canonical structural protein genes (N, P, M, G and L); however, there was remarkable diversity in the number and location of other long ORFs. Across the data set, we identified 179 additional ORFs 180 nt in length of which 142 shared no detectable protein sequence similarity with any other protein in our data set or with those in public databases (S2 Table) . Interestingly, although substantial variation in the length of gene junctions was observed in several genera (including ephemeroviruses and lyssaviruses), most variation in genome size occurred as the result of the presence of new, non-canonical ORFs in the regions between the structural protein genes (Table 1) . doi = 10.1371/journal.ppat.1004664 id = cord-278511-je1509ar author = Wang, David title = 5 challenges in understanding the role of the virome in health and disease date = 2020-03-26 keywords = virome; virus summary = An even more significant problem is that in most virome studies, more than 50% of the sequences in virus-enriched preparations have no detectable sequence similarity to any known reference sequences; these unalignable sequences are referred to as viral "dark matter" [8] and may include novel, highly divergent viruses that are unrecognizable. To illustrate this point, the United States National Institutes of Health (NIH) virology study sections address only "non-bacteriophage viral genetics, infection and replication, cellular and host responses to viral infections, and mechanisms of viral disease pathogenesis." Thus, there is a great need to bring these disparate communities together in order to collectively attack questions associated with the virome, especially as more complex trans-kingdom interactions are identified linking phages, bacteria, eukaryotic viruses, and eukaryotic cells. With new cell-culture systems and animal models for novel viruses, there will ideally be studies that attribute causal roles for some of the associations. doi = 10.1371/journal.ppat.1008318 id = cord-328947-3l9ydspz author = Webb, L. G. title = Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date = 2020-10-15 keywords = CHIKV; Fig; IFN; RNA; cgas; dna; sting summary = CHIKV is no exception, the type-I interferon (IFN) response has been demonstrated to be key in controlling CHIKV infection [21] [22] [23] [24] [25] [26] and primary sensing of the virus is via the pattern recognition receptor (PRR) retinoic acid-inducible gene I (RIG-I)-mitochondrial antiviral signaling protein (MAVS) axis [24, 26] . The lack of cGAS degradation seen in the exogenous expression system when compared to the infected cells shows that although there is a clear interaction of cGAS with nsP4, the degradation of cGAS observed is not mediated by the non-structural proteins of CHIKV, but must require other viral or host factors. Chikungunya virus inhibits DNA sensing by degrading cGAS both mock and infected cells by 4 hpi suggesting that the stress produced during the process of infection (mock or CHIKV) in HFF-1s stimulates increased translation at early timepoints ( Fig 4D, lanes 2 and 5) . doi = 10.1371/journal.ppat.1008999 id = cord-306624-1mjmttec author = Wodrich, Harald title = A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry date = 2010-03-19 keywords = MTOC; Nedd4.2; figure; protein summary = doi = 10.1371/journal.ppat.1000808 id = cord-010762-c01wgg4v author = Wu, Jiqin title = A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase date = 2020-05-01 keywords = Fig; JEV; RNA; denv2; ns5 summary = doi = 10.1371/journal.ppat.1008484 id = cord-348799-qu4zin3o author = Wu, Nannan title = The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation date = 2019-10-10 keywords = Fig; GFP; HEK293; ISG20; RNA; cell summary = This lack of specificity was not present in cells however, given that the ectopic expression of ISG20 did not lead to the indiscriminate degradation of cellular RNAs (ribosomal as well as small nucleolar RNAs previously shown to be associated to ISG20 [2] ), nor of an Hepatitis C virus (HCV)-derived Luciferase reporter mRNA produced in vitro and then transfected into cells (S4C and S4D Fig) , suggesting that in cells the RNase activity of ISG20 is tightly controlled. Self mimicry allows the escape of target genes'' mRNAs from the effects of ISG20 VSV infection and ectopic DNA or RNA transfection do not bear much in common apart from the fact that both represent artificial injections into the cell of non-self genetic material from without. To further determine whether ISG20 acted on translation initiation and more specifically through specific initiation factors (eIFs), capped and polyadenylated mRNAs coding luciferase under the control of several 5'' untranslated regions (5'' UTRs) were generated in vitro and directly transfected in ISG20-expressing cells (Fig 3D) . doi = 10.1371/journal.ppat.1008093 id = cord-331802-wo462anq author = Xia, Hongjie title = Human Enterovirus Nonstructural Protein 2C(ATPase) Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone date = 2015-07-28 keywords = ATP; ATPase; EV71; Fig; RNA summary = Herein, we report that the nonstructural protein 2C(ATPase) of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. Herein, we report that although bacterially expressed EV71 2C ATPase did not exhibit any RNA remodeling activity, eukaryotically expressed EV71 2C ATPase functions not only as an RNA helicase that unwinds RNA helices from 3 0 to 5 0 in an ATP-dependent manner but also as an RNA chaperone that destabilizes helices from either direction and facilitates strand annealing and complex RNA structure formation independently of ATP. doi = 10.1371/journal.ppat.1005067 id = cord-351389-48tszqh5 author = Xu, Kai title = Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody date = 2013-10-10 keywords = CDR; Hendra; hev summary = title: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. We used X-ray crystallography to determine the high-resolution structures of the Hendra virus G glycoprotein in complex with a cross-reactive neutralizing human monoclonal antibody. Taken together, the success of hmAb m102.4 in vivo as an effective post-exposure treatment against henipavirus disease in two different well-characterized animal models (the ferret and nonhuman primate), along with the new detailed structural findings on its viral G glycoprotein binding features that help explain its superior cross-reactive neutralizing activity, will facilitate efforts aimed at obtaining approved human use application to treat accidental exposure to HeV or NiV infection. doi = 10.1371/journal.ppat.1003684 id = cord-293164-i50cgkvq author = Zhou, Bin title = Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus date = 2014-10-02 keywords = Bat09; Fig; PB2; PR8 summary = doi = 10.1371/journal.ppat.1004420 id = cord-001992-m4k20i7g author = Ziegler, Christopher M. title = The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles date = 2016-03-24 keywords = Fig; LCMV; PPXY; VPS4B; Y88 summary = We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. Given the important role of the LCMV matrix protein and its late domain motif in regulating viral budding [10, 11] , we next investigated the specific effect these point mutations had on Z''s budding efficiency in a VLP release assay. To investigate the protein and genome composition of virions containing mutated late domains, an equivalent quantity of cell-free infectious virus particles from each rLCMV strain was concentrated for screening. Limiting dilutions of this UV-treated sample were applied to Vero E6 cells, followed by the addition of a fixed quantity of LCMV PFUs. As shown in Fig 5A, this allows for the determination of LCMV DI particle activity and is expressed as plaque interfering units 50 (PIU 50 ) per mL of a given sample. doi = 10.1371/journal.ppat.1005501 id = cord-260729-b12v3c8c author = de Lang, Anna title = Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques date = 2007-08-10 keywords = CoV; IFN; SARS; lung; stat1 summary = doi = 10.1371/journal.ppat.0030112 id = cord-000354-05lnj3w0 author = de Vries, Erik title = Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway date = 2011-03-31 keywords = DYNA; FCS; Fig; IAV; IND; PBS; entry summary = doi = 10.1371/journal.ppat.1001329