{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:00:43Z","timestamp":1776837643294,"version":"3.51.2"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council Australia","award":["1125704"],"award-info":[{"award-number":["1125704"]}]},{"name":"National Health and Medical Research Council Australia","award":["1079211"],"award-info":[{"award-number":["1079211"]}]},{"name":"National Health and Medical Research Council Australia","award":["1160838"],"award-info":[{"award-number":["1160838"]}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["DP150102569"],"award-info":[{"award-number":["DP150102569"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Miegunyah Trust Grimwade Fellowship"},{"name":"Australian Government Research Training Program"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Many viruses target signal transducers and activators of transcription (STAT) 1 and 2 to antagonise antiviral interferon signalling, but targeting of signalling by other STATs\/cytokines, including STAT3\/interleukin 6 that regulate processes important to Ebola virus (EBOV) haemorrhagic fever, is poorly defined. We report that EBOV potently inhibits STAT3 responses to interleukin-6 family cytokines, and that this is mediated by the interferon-antagonist VP24. Mechanistic analysis indicates that VP24 effects a unique strategy combining distinct karyopherin-dependent and karyopherin-independent mechanisms to antagonise STAT3-STAT1 heterodimers and STAT3 homodimers, respectively. This appears to reflect distinct mechanisms of nuclear trafficking of the STAT3 complexes, revealed for the first time by our analysis of VP24 function. These findings are consistent with major roles for global inhibition of STAT3 signalling in EBOV infection, and provide new insights into the molecular mechanisms of STAT3 nuclear trafficking, significant to pathogen-host interactions, cell physiology and pathologies such as cancer.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009636","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T13:26:47Z","timestamp":1624541207000},"page":"e1009636","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Antagonism of STAT3 signalling by Ebola virus"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0331-9522","authenticated-orcid":true,"given":"Angela R.","family":"Harrison","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn","family":"Todd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Dearnley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5571-6733","authenticated-orcid":true,"given":"Cassandra T.","family":"David","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M.","family":"Rawlinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-8875","authenticated-orcid":true,"given":"Gough G.","family":"Au","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3469-1837","authenticated-orcid":true,"given":"Glenn A.","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4516-3906","authenticated-orcid":true,"given":"Gregory W.","family":"Moseley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"ppat.1009636.ref001","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev-pathol-052016-100506","article-title":"The Pathogenesis of Ebola Virus Disease","volume":"12","author":"L Baseler","year":"2017","journal-title":"Annu Rev Pathol"},{"issue":"4","key":"ppat.1009636.ref002","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1093\/femsre\/fuw010","volume":"40","author":"R Burk","year":"2016","journal-title":"FEMS Microbiol Rev"},{"key":"ppat.1009636.ref003","unstructured":"World Health Organization. Ebola situation report. 2016."},{"key":"ppat.1009636.ref004","unstructured":"World Health Organization. Ebola situation reports: Democratic Republic of the Congo. 2020."},{"key":"ppat.1009636.ref005","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.3389\/fimmu.2017.01758","article-title":"Interplay between Janus Kinase\/Signal Transducer and Activator of Transcription Signaling Activated by Type I Interferons and Viral Antagonism","volume":"8","author":"Y Nan","year":"2017","journal-title":"Front Immunol"},{"issue":"6","key":"ppat.1009636.ref006","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1128\/JVI.80.6.3009-3020.2006","article-title":"Global suppression of the host antiviral response by Ebola- and Marburgviruses: increased antagonism of the type I interferon response is associated with enhanced virulence","volume":"80","author":"JC Kash","year":"2006","journal-title":"Journal of virology"},{"issue":"7","key":"ppat.1009636.ref007","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1371\/journal.ppat.0020073","article-title":"Molecular determinants of Ebola virus virulence in mice","volume":"2","author":"H Ebihara","year":"2006","journal-title":"PLoS pathogens"},{"issue":"23","key":"ppat.1009636.ref008","doi-asserted-by":"crossref","first-page":"7067","DOI":"10.1093\/emboj\/16.23.7067","article-title":"Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1","volume":"16","author":"T Sekimoto","year":"1997","journal-title":"The EMBO journal"},{"issue":"19","key":"ppat.1009636.ref009","doi-asserted-by":"crossref","first-page":"16447","DOI":"10.1074\/jbc.M008821200","article-title":"Arginine\/lysine-rich structural element is involved in interferon-induced nuclear import of STATs","volume":"276","author":"K Melen","year":"2001","journal-title":"The Journal of biological chemistry"},{"issue":"30","key":"ppat.1009636.ref010","doi-asserted-by":"crossref","first-page":"28193","DOI":"10.1074\/jbc.M303571200","article-title":"Importin alpha nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein","volume":"278","author":"K Melen","year":"2003","journal-title":"The Journal of biological chemistry"},{"issue":"2","key":"ppat.1009636.ref011","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3109\/08977194.2012.660936","article-title":"Biology and significance of the JAK\/STAT signalling pathways","volume":"30","author":"H Kiu","year":"2012","journal-title":"Growth Factors"},{"issue":"11","key":"ppat.1009636.ref012","doi-asserted-by":"crossref","first-page":"5156","DOI":"10.1128\/JVI.02349-05","article-title":"Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation","volume":"80","author":"SP Reid","year":"2006","journal-title":"Journal of virology"},{"issue":"24","key":"ppat.1009636.ref013","doi-asserted-by":"crossref","first-page":"13469","DOI":"10.1128\/JVI.01097-07","article-title":"Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin alpha proteins with activated STAT1","volume":"81","author":"SP Reid","year":"2007","journal-title":"Journal of virology"},{"issue":"2","key":"ppat.1009636.ref014","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1128\/JVI.01372-09","article-title":"Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling","volume":"84","author":"M Mateo","year":"2010","journal-title":"Journal of virology"},{"issue":"2","key":"ppat.1009636.ref015","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.chom.2014.07.008","article-title":"Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1","volume":"16","author":"W Xu","year":"2014","journal-title":"Cell Host Microbe"},{"issue":"11","key":"ppat.1009636.ref016","doi-asserted-by":"crossref","first-page":"6385","DOI":"10.1128\/JVI.77.11.6385-6393.2003","article-title":"STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling","volume":"77","author":"CM Ulane","year":"2003","journal-title":"Journal of virology"},{"issue":"13","key":"ppat.1009636.ref017","doi-asserted-by":"crossref","first-page":"7635","DOI":"10.1128\/JVI.77.13.7635-7644.2003","article-title":"STAT protein interference and suppression of cytokine signal transduction by measles virus V protein","volume":"77","author":"H Palosaari","year":"2003","journal-title":"Journal of virology"},{"issue":"14","key":"ppat.1009636.ref018","doi-asserted-by":"crossref","first-page":"8261","DOI":"10.1128\/JVI.00989-13","article-title":"The rabies virus interferon antagonist P protein interacts with activated STAT3 and inhibits Gp130 receptor signaling","volume":"87","author":"KG Lieu","year":"2013","journal-title":"Journal of virology"},{"issue":"1","key":"ppat.1009636.ref019","doi-asserted-by":"crossref","first-page":"e53881","DOI":"10.1371\/journal.pone.0053881","article-title":"The V protein of Tioman virus is incapable of blocking type I interferon signaling in human cells","volume":"8","author":"G Caignard","year":"2013","journal-title":"PloS one"},{"issue":"9","key":"ppat.1009636.ref020","doi-asserted-by":"crossref","first-page":"e1008767","DOI":"10.1371\/journal.ppat.1008767","article-title":"Lyssavirus P-protein selectively targets STAT3-STAT1 heterodimers to modulate cytokine signalling","volume":"16","author":"AR Harrison","year":"2020","journal-title":"PLoS pathogens"},{"issue":"11","key":"ppat.1009636.ref021","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/nrmicro3524","article-title":"Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus","volume":"13","author":"I Messaoudi","year":"2015","journal-title":"Nat Rev Microbiol"},{"issue":"10","key":"ppat.1009636.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0000837","article-title":"Human fatal zaire ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis","volume":"4","author":"N Wauquier","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"7601","key":"ppat.1009636.ref023","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature17949","article-title":"Unique human immune signature of Ebola virus disease in Guinea","volume":"533","author":"P Ruibal","year":"2016","journal-title":"Nature"},{"issue":"23","key":"ppat.1009636.ref024","doi-asserted-by":"crossref","first-page":"8150","DOI":"10.1073\/pnas.0501643102","article-title":"STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-alpha 3","volume":"102","author":"L Liu","year":"2005","journal-title":"PNAS"},{"issue":"4","key":"ppat.1009636.ref025","doi-asserted-by":"crossref","first-page":"e27080","DOI":"10.4161\/jkst.27080","article-title":"STATs get their move on","volume":"2","author":"NC Reich","year":"2013","journal-title":"Jak-stat"},{"issue":"8","key":"ppat.1009636.ref026","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.cellsig.2005.06.016","article-title":"Regulation of Stat3 nuclear import by importin alpha5 and importin alpha7 via two different functional sequence elements","volume":"18","author":"J Ma","year":"2006","journal-title":"Cellular signalling"},{"issue":"3","key":"ppat.1009636.ref027","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.bbrc.2005.03.063","article-title":"Extracellular signal-dependent nuclear import of STAT3 is mediated by various importin alphas","volume":"330","author":"R Ushijima","year":"2005","journal-title":"Biochemical and biophysical research communications"},{"issue":"8","key":"ppat.1009636.ref028","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.cellsig.2016.03.011","article-title":"Dissecting functions of the N-terminal domain and GAS-site recognition in STAT3 nuclear trafficking","volume":"28","author":"A Martincuks","year":"2016","journal-title":"Cellular signalling"},{"issue":"1","key":"ppat.1009636.ref029","doi-asserted-by":"crossref","first-page":"e23060","DOI":"10.4161\/jkst.23060","article-title":"STAT heterodimers in immunity: A mixed message or a unique signal?","volume":"2","author":"GM Delgoffe","year":"2013","journal-title":"Jak-stat"},{"key":"ppat.1009636.ref030","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/srep01206","article-title":"The spatio-temporal distribution dynamics of Ebola virus proteins and RNA in infected cells","volume":"3","author":"A Nanbo","year":"2013","journal-title":"Sci Rep"},{"issue":"2","key":"ppat.1009636.ref031","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.bbrc.2004.09.081","article-title":"STAT3 induces anti-hepatitis C viral activity in liver cells","volume":"324","author":"H Zhu","year":"2004","journal-title":"Biochemical and biophysical research communications"},{"issue":"4","key":"ppat.1009636.ref032","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1189\/jlb.4A1016-199RR","article-title":"Signal transducer and activator of transcription 3 (Stat3) regulates host defense and protects mice against herpes simplex virus-1 (HSV-1) infection","volume":"101","author":"HC Hsia","year":"2017","journal-title":"Journal of leukocyte biology"},{"issue":"22","key":"ppat.1009636.ref033","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1161\/CIRCULATIONAHA.106.642454","article-title":"Innate defense mechanism against virus infection within the cardiac myocyte requiring gp130-STAT3 signaling","volume":"114","author":"T Yajima","year":"2006","journal-title":"Circulation"},{"issue":"9","key":"ppat.1009636.ref034","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1007\/s00018-016-2435-3","article-title":"A novel anti-viral role for STAT3 in IFN-alpha signalling responses","volume":"74","author":"R Mahony","year":"2017","journal-title":"Cell Mol Life Sci"},{"issue":"5","key":"ppat.1009636.ref035","doi-asserted-by":"crossref","first-page":"954","DOI":"10.4269\/ajtmh.2010.09-0636","article-title":"Comprehensive panel of real-time TaqMan polymerase chain reaction assays for detection and absolute quantification of filoviruses, arenaviruses, and New World hantaviruses","volume":"82","author":"AR Trombley","year":"2010","journal-title":"Am J Trop Med Hyg"},{"issue":"5155","key":"ppat.1009636.ref036","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1126\/science.8140422","article-title":"Stat3: A STAT Family Member Activated by Tyrosine Phosphorylation in Response to Epidermal Growth Factor and Interleukin-6","volume":"264","author":"Z Zhong","year":"1994","journal-title":"Science"},{"issue":"11","key":"ppat.1009636.ref037","first-page":"4605","article-title":"Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway","volume":"9","author":"S Pellegrini","year":"1989","journal-title":"Molecular and cellular biology"},{"issue":"24","key":"ppat.1009636.ref038","doi-asserted-by":"crossref","first-page":"11455","DOI":"10.1073\/pnas.88.24.11455","article-title":"High-frequency mutagenesis of human cells and characterization of a mutant unresponsive to both alpha and gamma interferons","volume":"88","author":"R McKendry","year":"1991","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"ppat.1009636.ref039","doi-asserted-by":"crossref","first-page":"7698","DOI":"10.1038\/s41598-017-08167-8","article-title":"Ebola virus VP24 interacts with NP to facilitate nucleocapsid assembly and genome packaging","volume":"7","author":"L Banadyga","year":"2017","journal-title":"Sci Rep"},{"issue":"8","key":"ppat.1009636.ref040","doi-asserted-by":"crossref","first-page":"4227","DOI":"10.1128\/JVI.00154-15","article-title":"Disruption of type I interferon signaling by the nonstructural protein of severe fever with thrombocytopenia syndrome virus via the hijacking of STAT2 and STAT1 into inclusion bodies","volume":"89","author":"YJ Ning","year":"2015","journal-title":"Journal of virology"},{"issue":"6","key":"ppat.1009636.ref041","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1128\/JVI.03510-13","article-title":"Evasion of antiviral immunity through sequestering of TBK1\/IKKepsilon\/IRF3 into viral inclusion bodies","volume":"88","author":"X Wu","year":"2014","journal-title":"Journal of virology"},{"issue":"22","key":"ppat.1009636.ref042","doi-asserted-by":"crossref","first-page":"e00856","DOI":"10.1128\/JVI.00856-20","article-title":"The dynamic interface of viruses with STATs","volume":"94","author":"AR Harrison","year":"2020","journal-title":"Journal of virology"},{"issue":"18","key":"ppat.1009636.ref043","doi-asserted-by":"crossref","first-page":"10194","DOI":"10.1128\/JVI.01249-12","article-title":"Conservation of a unique mechanism of immune evasion across the Lyssavirus genus","volume":"86","author":"L Wiltzer","year":"2012","journal-title":"Journal of virology"},{"issue":"7","key":"ppat.1009636.ref044","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1016\/j.celrep.2019.10.020","article-title":"Structural Elucidation of Viral Antagonism of Innate Immunity at the STAT1 Interface","volume":"29","author":"MA Hossain","year":"2019","journal-title":"Cell Rep"},{"issue":"8","key":"ppat.1009636.ref045","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1128\/JVI.01930-06","article-title":"The nucleocytoplasmic rabies virus P protein counteracts interferon signaling by inhibiting both nuclear accumulation and DNA binding of STAT1","volume":"81","author":"A Vidy","year":"2007","journal-title":"Journal of virology"},{"issue":"13","key":"ppat.1009636.ref046","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1002\/j.1460-2075.1990.tb07898.x","article-title":"The SIF binding element confers sis\/PDGF inducibility onto the c-fos promoter","volume":"9","author":"BJ Wagner","year":"1990","journal-title":"The EMBO journal"},{"issue":"10","key":"ppat.1009636.ref047","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.bcp.2010.01.001","article-title":"A novel small-molecule disrupts Stat3 SH2 domain\u2013phosphotyrosine interactions and Stat3-dependent tumor processes","volume":"79","author":"X Zhang","year":"2010","journal-title":"Biochemical Pharmacology"},{"issue":"11","key":"ppat.1009636.ref048","doi-asserted-by":"crossref","first-page":"e13927","DOI":"10.1371\/journal.pone.0013927","article-title":"Influenza virus non-structural protein 1 (NS1) disrupts interferon signaling","volume":"5","author":"D Jia","year":"2010","journal-title":"PloS one"},{"issue":"2","key":"ppat.1009636.ref049","doi-asserted-by":"crossref","first-page":"e1002550","DOI":"10.1371\/journal.ppat.1002550","article-title":"The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold","volume":"8","author":"AP Zhang","year":"2012","journal-title":"PLoS pathogens"},{"issue":"11","key":"ppat.1009636.ref050","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1021\/pr500556d","article-title":"Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host-cell protein function","volume":"13","author":"I Garcia-Dorival","year":"2014","journal-title":"J Proteome Res"},{"issue":"7408","key":"ppat.1009636.ref051","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature11289","article-title":"Viral immune modulators perturb the human molecular network by common and unique strategies","volume":"487","author":"A Pichlmair","year":"2012","journal-title":"Nature"},{"key":"ppat.1009636.ref052","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1042\/bj20030708","article-title":"Analysis of Stat3 (signal transducer and activator of transcription 3) dimerization by fluorescence resonance energy transfer in living cells","volume":"377","author":"AK Kretzschmar","year":"2004","journal-title":"The Biochemical journal"},{"key":"ppat.1009636.ref053","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1046\/j.1365-2249.2002.01800.x","article-title":"Inflammatory responses in Ebola virus-infected patients","volume":"128","author":"S Baize","year":"2002","journal-title":"Clin Exp Immunol"},{"key":"ppat.1009636.ref054","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1086\/514283","article-title":"Markedly Elevated Levels of Interferon (IFN)-g, IFN-a, Interleukin (IL)-2, IL- 10, and Tumor Necrosis Factor-a Associated with Fatal Ebola Virus Infection","volume":"179","author":"F Villinger","year":"1999","journal-title":"The Journal of infectious diseases"},{"issue":"11","key":"ppat.1009636.ref055","doi-asserted-by":"crossref","DOI":"10.3390\/v11111016","article-title":"A Single Point Mutation in the Mumps V Protein Alters Targeting of the Cellular STAT Pathways Resulting in Virus Attenuation","volume":"11","author":"T Malik","year":"2019","journal-title":"Viruses"},{"key":"ppat.1009636.ref056","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.3389\/fimmu.2019.01843","article-title":"Influenza Virus-Induced Robust Expression of SOCS3 Contributes to Excessive Production of IL-6","volume":"10","author":"S Liu","year":"2019","journal-title":"Front Immunol"},{"issue":"1","key":"ppat.1009636.ref057","doi-asserted-by":"crossref","first-page":"e1000721","DOI":"10.1371\/journal.ppat.1000721","article-title":"Marburg virus evades interferon responses by a mechanism distinct from ebola virus","volume":"6","author":"C Valmas","year":"2010","journal-title":"PLoS pathogens"},{"issue":"1","key":"ppat.1009636.ref058","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12985-018-0985-8","article-title":"Ebolavirus diagnosis made simple, comparable and faster than molecular detection methods: preparing for the future","volume":"15","author":"AS James","year":"2018","journal-title":"Virol J"},{"issue":"11","key":"ppat.1009636.ref059","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1093\/infdis\/jit829","article-title":"Interaction of Rabies Virus P-Protein With STAT Proteins is Critical to Lethal Rabies Disease","volume":"209","author":"L Wiltzer","year":"2014","journal-title":"The Journal of infectious diseases"},{"issue":"18","key":"ppat.1009636.ref060","doi-asserted-by":"crossref","first-page":"9499","DOI":"10.1073\/pnas.93.18.9499","article-title":"Inhibition of cytokines and JAK-STAT activation by distinct signaling pathways","volume":"93","author":"TK Sengupta","year":"1996","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"ppat.1009636.ref061","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1128\/JB.182.1.57-66.2000","article-title":"The VirR Response Regulator from Clostridium perfringens Binds Independently to Two Imperfect Direct Repeats Located Upstream of the pfoA Promoter","volume":"182","author":"JK Cheung","year":"2000","journal-title":"J Bacteriol"},{"issue":"6","key":"ppat.1009636.ref062","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"TD Schmittgen","year":"2008","journal-title":"Nature protocols"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009636","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T13:27:41Z","timestamp":1624541261000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009636"}},"subtitle":[],"editor":[{"given":"Alexander","family":"Bukreyev","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":62,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009636","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.10.245464","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,24]]}}}