{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T20:13:05Z","timestamp":1780344785282,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008874","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U24 EB028887"],"award-info":[{"award-number":["U24 EB028887"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM122424"],"award-info":[{"award-number":["R01 GM122424"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1720625"],"award-info":[{"award-number":["1720625"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006976","name":"lilly endowment","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006976","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1943777"],"award-info":[{"award-number":["1943777"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Respiratory viruses present major public health challenges, as evidenced by the 1918 Spanish Flu, the 1957 H2N2, 1968 H3N2, and 2009 H1N1 influenza pandemics, and the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Severe RNA virus respiratory infections often correlate with high viral load and excessive inflammation. Understanding the dynamics of the innate immune response and its manifestations at the cell and tissue levels is vital to understanding the mechanisms of immunopathology and to developing strain-independent treatments. Here, we present a novel spatialized multicellular computational model of RNA virus infection and the type-I interferon-mediated antiviral response that it induces within lung epithelial cells. The model is built using the CompuCell3D multicellular simulation environment and is parameterized using data from influenza virus-infected cell cultures. Consistent with experimental observations, it exhibits either linear radial growth of viral plaques or arrested plaque growth depending on the local concentration of type I interferons. The model suggests that modifying the activity of signaling molecules in the JAK\/STAT pathway or altering the ratio of the diffusion lengths of interferon and virus in the cell culture could lead to plaque growth arrest. The dependence of plaque growth arrest on diffusion lengths highlights the importance of developing validated spatial models of cytokine signaling and the need for <jats:italic>in vitro<\/jats:italic> measurement of these diffusion coefficients. Sensitivity analyses under conditions leading to continuous or arrested plaque growth found that plaque growth is more sensitive to variations of most parameters and more likely to have identifiable model parameters when conditions lead to plaque arrest. This result suggests that cytokine assay measurements may be most informative under conditions leading to arrested plaque growth. The model is easy to extend to include SARS-CoV-2-specific mechanisms or to use as a component in models linking epithelial cell signaling to systemic immune models.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008874","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T17:35:16Z","timestamp":1635183316000},"page":"e1008874","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Multicellular spatial model of RNA virus replication and interferon responses reveals factors controlling plaque growth dynamics"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5959-6302","authenticated-orcid":true,"given":"Josua O.","family":"Aponte-Serrano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2606-4147","authenticated-orcid":true,"given":"Jordan J. A.","family":"Weaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4274-656X","authenticated-orcid":true,"given":"T. J.","family":"Sego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3634-190X","authenticated-orcid":true,"given":"James A.","family":"Glazier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3315-7103","authenticated-orcid":true,"given":"Jason E.","family":"Shoemaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"key":"pcbi.1008874.ref001","unstructured":"World Health Organisation. Global Influenza Strategy Summary 2019\u20132030 Influenza. Glob Influ Strateg 2019\u20132030 Influ [Internet]. 2019 [cited 2020 Aug 5];1:1. Available from: https:\/\/apps.who.int\/iris\/handle\/10665\/311184"},{"key":"pcbi.1008874.ref002","unstructured":"THE GEOGRAPHY AND MORTALITY OF THE 1918 INFLUENZA PANDEMIC on JSTOR [Internet]. [cited 2020 Nov 30]. Available from: https:\/\/www.jstor.org\/stable\/44447656?seq=1#metadata_info_tab_contents"},{"key":"pcbi.1008874.ref003","unstructured":"Centro de Control y prevenci\u00f3n de enfermedades. 1957\u20131958 Pandemic (H2N2 virus) | Pandemic Influenza (Flu) | CDC [Internet]. CDC-Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases (NCIRD). 2019 [cited 2021 May 18]. Available from: https:\/\/www.cdc.gov\/flu\/pandemic-resources\/1957-1958-pandemic.html"},{"key":"pcbi.1008874.ref004","unstructured":"Centre for Disease Control and Prevention. 1968 Pandemic (H3N2 virus) | Pandemic Influenza (Flu) | CDC [Internet]. U.S. Department of Health & Human Services. 2019 [cited 2021 May 18]. Available from: https:\/\/www.cdc.gov\/flu\/pandemic-resources\/1968-pandemic.html"},{"key":"pcbi.1008874.ref005","unstructured":"CDC. 2009 H1N1 Pandemic (H1N1pdm09 virus) | Pandemic Influenza (Flu) | CDC [Internet]. Centers for Disease Control and Prevention. 2009 [cited 2021 May 18]. Available from: https:\/\/www.cdc.gov\/flu\/pandemic-resources\/2009-h1n1-pandemic.html"},{"key":"pcbi.1008874.ref006","unstructured":"World Health Organization. Weekly epidemiological update on COVID-19\u201322 June 2021 [Internet]. World Health Organization. 2020 [cited 2021 Jun 30]. Available from: https:\/\/www.who.int\/publications\/m\/item\/weekly-epidemiological-update-on-covid-19\u201429-june-2021"},{"issue":"4","key":"pcbi.1008874.ref007","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/cmi.2016.1","article-title":"Aberrant coagulation causes a hyper-inflammatory response in severe influenza pneumonia","volume":"13","author":"Y Yang","year":"2016","journal-title":"Cell Mol Immunol"},{"issue":"2","key":"pcbi.1008874.ref008","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/cei.13523","article-title":"Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage","volume":"202","author":"S Amor","year":"2020","journal-title":"Clin Exp Immunol"},{"key":"pcbi.1008874.ref009","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2147\/JIR.S267280","article-title":"Role of ifn and complements system: Innate immunity in sars-cov-2","volume":"13","author":"T Shibabaw","year":"2020","journal-title":"Journal of Inflammation Research"},{"key":"pcbi.1008874.ref010","article-title":"Possible molecular and paracrine involvement underlying the pathogenesis of COVID-19 cardiovascular complications.","author":"AF AbdelMassih","year":"2020","journal-title":"Cardiovasc Endocrinol Metab"},{"issue":"7125","key":"pcbi.1008874.ref011","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nature05495","article-title":"Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus","volume":"445","author":"D Kobasa","year":"2007","journal-title":"Nature"},{"issue":"9","key":"pcbi.1008874.ref012","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1073\/pnas.0813234106","article-title":"Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus","volume":"106","author":"CR Baskin","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"15","key":"pcbi.1008874.ref013","doi-asserted-by":"crossref","first-page":"7613","DOI":"10.1128\/JVI.00553-10","article-title":"Lethal Dissemination of H5N1 Influenza Virus Is Associated with Dysregulation of Inflammation and Lipoxin Signaling in a Mouse Model of Infection","volume":"84","author":"C Cilloniz","year":"2010","journal-title":"J Virol"},{"issue":"12","key":"pcbi.1008874.ref014","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.it.2009.09.004","article-title":"Innate immune responses to influenza A H5N1: friend or foe?","volume":"30","author":"JSM Peiris","year":"2009","journal-title":"Trends Immunol"},{"key":"pcbi.1008874.ref015","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1743-422X-8-97","article-title":"Toll-like receptor pre-stimulation protects mice against lethal infection with highly pathogenic influenza viruses","volume":"8","author":"K Shinya","year":"2011","journal-title":"Virol J"},{"key":"pcbi.1008874.ref016","article-title":"Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV.","author":"K Lokugamage","year":"2020","journal-title":"J Virol"},{"issue":"4","key":"pcbi.1008874.ref017","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.bpj.2009.10.049","article-title":"Immune response modeling of interferon beta-pretreated influenza virus-infected human dendritic cells","volume":"98","author":"L Qiao","year":"2010","journal-title":"Biophys J"},{"key":"pcbi.1008874.ref018","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.3389\/fimmu.2020.01061","article-title":"Interferon-\u03b12b Treatment for COVID-19.","volume":"11","author":"Q Zhou","year":"2020","journal-title":"Front Immunol"},{"key":"pcbi.1008874.ref019","unstructured":"Covid: Large trial of new treatment begins in UK\u2014BBC News [Internet]. [cited 2021 Jan 15]. Available from: https:\/\/www.bbc.com\/news\/health-55639096"},{"key":"pcbi.1008874.ref020","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jtbi.2018.11.001","article-title":"Mathematical modeling of the cGAS pathway reveals robustness of DNA sensing to TREX1 feedback","volume":"462","author":"RW Gregg","year":"2019","journal-title":"J Theor Biol"},{"issue":"6","key":"pcbi.1008874.ref021","doi-asserted-by":"crossref","first-page":"e1002588","DOI":"10.1371\/journal.pcbi.1002588","article-title":"Modeling within-host dynamics of influenza virus infection including immune responses","volume":"8","author":"KA Pawelek","year":"2012","journal-title":"PLoS Comput Biol"},{"issue":"4","key":"pcbi.1008874.ref022","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1006\/jtbi.1994.1074","article-title":"Mathematical Model of Antiviral Immune Response III. Influenza A Virus Infection","volume":"167","author":"GA Bocharov","year":"1994","journal-title":"J Theor Biol"},{"key":"pcbi.1008874.ref023","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.coisb.2018.10.005","article-title":"Validated models of immune response to virus infection","volume":"12","author":"AM Smith","year":"2018","journal-title":"Current Opinion in Systems Biology."},{"issue":"4","key":"pcbi.1008874.ref024","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3109\/08916934.2011.523267","article-title":"Design considerations in building in silico equivalents of common experimental influenza virus assays","volume":"44","author":"BP Holder","year":"2011","journal-title":"Autoimmunity"},{"issue":"8","key":"pcbi.1008874.ref025","doi-asserted-by":"crossref","first-page":"3974","DOI":"10.1128\/JVI.02078-09","article-title":"Dynamics of Influenza Virus Infection and Pathology","volume":"84","author":"RA Saenz","year":"2010","journal-title":"J Virol"},{"issue":"1","key":"pcbi.1008874.ref026","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jtbi.2006.12.015","article-title":"A dynamical model of human immune response to influenza A virus infection","volume":"246","author":"B Hancioglu","year":"2007","journal-title":"J Theor Biol"},{"issue":"6","key":"pcbi.1008874.ref027","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1172\/JCI132583","article-title":"Tissue-resident T cell-derived cytokines eliminate herpes simplex virus-2-infected cells","volume":"130","author":"P Roychoudhury","year":"2020","journal-title":"J Clin Invest"},{"issue":"10","key":"pcbi.1008874.ref028","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1093\/bioinformatics\/btaa969","article-title":"Agent-based modeling reveals benefits of heterogeneous and stochastic cell populations during cGAS-mediated IFN\u03b2 production","volume":"37","author":"RW Gregg","year":"2021","journal-title":"Bioinformatics"},{"key":"pcbi.1008874.ref029","first-page":"325","article-title":"Multi-Scale Modeling of Tissues Using CompuCell3D","author":"MH Swat","year":"2012","journal-title":"In: Methods in Cell Biology"},{"issue":"3","key":"pcbi.1008874.ref030","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1128\/am.26.3.344-348.1973","article-title":"In Vitro Studies with Modoc Virus in Vero Cells: Plaque Assay and Kinetics of Growth, Neutralization, and Thermal Inactivation.","volume":"26","author":"JW Davis","year":"1973","journal-title":"Appl Microbiol"},{"key":"pcbi.1008874.ref031","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-60327-164-6_7","article-title":"Enumeration of bacteriophages by double agar overlay plaque assay","volume":"501","author":"AM Kropinski","year":"2009","journal-title":"Methods Mol Biol"},{"issue":"1","key":"pcbi.1008874.ref032","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/BF02123574","article-title":"Permanent canine kidney (MDCK) cells for isolation and plaque assay of influenza B viruses.","volume":"162","author":"K. Tobita","year":"1975","journal-title":"Med Microbiol Immunol"},{"issue":"7098","key":"pcbi.1008874.ref033","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/S0140-6736(59)91362-5","article-title":"A SIMPLE PLAQUE INHIBITION TEST FOR ANTIVIRAL AGENTS: APPLICATION TO ASSAY OF INTERFERON","volume":"274","author":"JS Porterfield","year":"1959","journal-title":"Lancet"},{"issue":"2","key":"pcbi.1008874.ref034","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3181\/00379727-132-34264","article-title":"Antitrinitrophenyl (TNP) Plaque Assay. Primary Response of Balb\/c Mice to Soluble and Particulate Immunogen.","volume":"132","author":"MB Rittenberg","year":"1969","journal-title":"Exp Biol Med"},{"issue":"3","key":"pcbi.1008874.ref035","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/0042-6822(63)90068-0","article-title":"Studies on vaccinia virus plaque formation and its inhibition by interferon. III. A simplified plaque inhibition assay of interferon","volume":"19","author":"J Lindenmann","year":"1963","journal-title":"Virology"},{"issue":"5","key":"pcbi.1008874.ref036","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1128\/AAC.17.5.865","article-title":"Plaque inhibition assay for drug susceptibility testing of influenza viruses","volume":"17","author":"FG Hayden","year":"1980","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"pcbi.1008874.ref037","first-page":"1","article-title":"Mathematical modeling of rna virus sensing pathways reveals paracrine signaling as the primary factor regulating excessive cytokine production","volume":"8","author":"JJA Weaver","year":"2020","journal-title":"Processes"},{"key":"pcbi.1008874.ref038","first-page":"429","article-title":"Influenza A virus infection kinetics: Quantitative data and models","volume":"3","author":"AM Smith","year":"2011","journal-title":"Internet]Wiley Interdisciplinary Reviews: Systems Biology and Medicine"},{"issue":"3","key":"pcbi.1008874.ref039","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.cell.2010.01.041","article-title":"SnapShot: Pathways of Antiviral Innate Immunity","volume":"140","author":"L Sun","year":"2010","journal-title":"Cell"},{"key":"pcbi.1008874.ref040","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.3389\/fimmu.2018.01581","article-title":"Influenza A virus cell entry, replication, virion assembly and movement [Internet].","author":"D Dou","year":"2018","journal-title":"9, Frontiers in Immunology."},{"issue":"1","key":"pcbi.1008874.ref041","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0042-6822(66)90195-4","article-title":"Early events in the eclipse phase of influenza and parainfluenza virus infection","volume":"29","author":"DO White","year":"1966","journal-title":"Virology"},{"issue":"15","key":"pcbi.1008874.ref042","doi-asserted-by":"crossref","first-page":"7590","DOI":"10.1128\/JVI.01623-05","article-title":"Kinetics of influenza A virus infection in humans","volume":"80","author":"P Baccam","year":"2006","journal-title":"J Virol"},{"key":"pcbi.1008874.ref043","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: A complex web of host defenses","volume":"32","author":"WM Schneider","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"pcbi.1008874.ref044","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.coviro.2012.04.004","article-title":"SARS coronavirus pathogenesis: Host innate immune responses and viral antagonism of interferon","volume":"2","author":"AL Totura","year":"2012","journal-title":"Current Opinion in Virology."},{"issue":"10","key":"pcbi.1008874.ref045","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1084\/jem.20101664","article-title":"Type I interferon: friend or foe?","volume":"207","author":"G. Trinchieri","year":"2010","journal-title":"J Exp Med"},{"issue":"4","key":"pcbi.1008874.ref046","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1111\/j.1462-5822.2006.00841.x","article-title":"IFN\u03b2 induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein","volume":"9","author":"B Opitz","year":"2007","journal-title":"Cell Microbiol"},{"key":"pcbi.1008874.ref047","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.virol.2015.03.048","article-title":"RIG-I and TLR3 are both required for maximum interferon induction by influenza virus in human lung alveolar epithelial cells","volume":"482","author":"W Wu","year":"2015","journal-title":"Virology"},{"issue":"6","key":"pcbi.1008874.ref048","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.chom.2014.11.002","article-title":"Influenza virus-host interactome screen as a platform for antiviral drug development","volume":"16","author":"T Watanabe","year":"2014","journal-title":"Cell Host Microbe"},{"issue":"7","key":"pcbi.1008874.ref049","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.cell.2009.12.018","article-title":"A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection","volume":"139","author":"SD Shapira","year":"2009","journal-title":"Cell"},{"issue":"6","key":"pcbi.1008874.ref050","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1529\/biophysj.107.109736","article-title":"Time and length scales of autocrine signals in three dimensions","volume":"93","author":"M Coppey","year":"2007","journal-title":"Biophys J"},{"issue":"1","key":"pcbi.1008874.ref051","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/dnares\/dsn030","article-title":"Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells","volume":"16","author":"L V. Sharova","year":"2009","journal-title":"DNA Res"},{"issue":"1","key":"pcbi.1008874.ref052","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bbrc.2006.01.122","article-title":"Regulation of IRF7 through cell type-specific protein stability","volume":"342","author":"A Prakash","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"pcbi.1008874.ref053","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/jcp.1040690309","article-title":"Correlation between cell enlargement and nucleic acid and protein content of hela cells in unbalanced growth produced by inhibitors of DNA synthesis","volume":"69","author":"LS Cohen","year":"1967","journal-title":"J Cell Physiol"},{"issue":"12","key":"pcbi.1008874.ref054","doi-asserted-by":"crossref","first-page":"5275","DOI":"10.1021\/pr101183k","article-title":"Systems-wide proteomic analysis in mammalian cells reveals conserved, functional protein turnover","volume":"10","author":"SB Cambridge","year":"2011","journal-title":"J Proteome Res"},{"issue":"12","key":"pcbi.1008874.ref055","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.micinf.2017.08.009","article-title":"Andrographolide inhibits influenza A virus-induced inflammation in a murine model through NF-\u03baB and JAK-STAT signaling pathway","volume":"19","author":"Y Ding","year":"2017","journal-title":"Microbes Infect"},{"issue":"5","key":"pcbi.1008874.ref056","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.chom.2009.04.006","article-title":"Influenza A Virus NS1 Targets the Ubiquitin Ligase TRIM25 to Evade Recognition by the Host Viral RNA Sensor RIG-I.","volume":"5","author":"MU Gack","year":"2009","journal-title":"Cell Host Microbe"},{"issue":"11","key":"pcbi.1008874.ref057","doi-asserted-by":"crossref","first-page":"e1003059","DOI":"10.1371\/journal.ppat.1003059","article-title":"Species-Specific Inhibition of RIG-I Ubiquitination and IFN Induction by the Influenza A Virus NS1 Protein","volume":"8","author":"R Rajsbaum","year":"2012","journal-title":"PLoS Pathog"},{"issue":"6","key":"pcbi.1008874.ref058","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.molcel.2020.10.034","article-title":"Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA","volume":"80","author":"S Yuan","year":"2020","journal-title":"Mol Cell"},{"issue":"1","key":"pcbi.1008874.ref059","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1128\/JVI.06168-11","article-title":"The TLR4-TRIF Pathway Protects against H5N1 Influenza Virus Infection.","volume":"86","author":"K Shinya","year":"2012","journal-title":"J Virol"},{"issue":"1","key":"pcbi.1008874.ref060","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms4864","article-title":"Pathogenic potential of interferon \u03b1\u03b2 in acute influenza infection.","volume":"5","author":"S Davidson","year":"2014","journal-title":"Nat Commun"},{"issue":"5801","key":"pcbi.1008874.ref061","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1126\/science.1132998","article-title":"RIG-I-mediated antiviral responses to single-stranded RNA bearing 5\u2032-phosphates","volume":"314","author":"A Pichlmair","year":"2006","journal-title":"Science (80-)"},{"issue":"3","key":"pcbi.1008874.ref062","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1084\/jem.79.3.267","article-title":"The size of influenza virus","volume":"79","author":"WM Stanley","year":"1944","journal-title":"J Exp Med"},{"issue":"5779","key":"pcbi.1008874.ref063","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/287193a0","article-title":"Expression of human fibroblast interferon gene in escherichia coli","volume":"287","author":"R Derynck","year":"1980","journal-title":"Nature"},{"issue":"14","key":"pcbi.1008874.ref064","article-title":"Influenza A Virus Infection Triggers Pyroptosis and Apoptosis of Respiratory Epithelial Cells through the Type I Interferon Signaling Pathway in a Mutually Exclusive Manner","volume":"92","author":"S Lee","year":"2018","journal-title":"J Virol"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1008874","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008874","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T18:38:12Z","timestamp":1637606292000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008874"}},"subtitle":[],"editor":[{"given":"Sergei L.","family":"Kosakovsky Pond","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,25]]},"references-count":64,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1008874","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1008874","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,25]]}}}