{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:22Z","timestamp":1787022202459,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1007867","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R21 AI111115"],"award-info":[{"award-number":["R21 AI111115"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01 AI095436"],"award-info":[{"award-number":["R01 AI095436"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"crossref","award":["HDTRA1-15-01-0047"],"award-info":[{"award-number":["HDTRA1-15-01-0047"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R21 AI132909"],"award-info":[{"award-number":["R21 AI132909"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1007867","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T13:41:03Z","timestamp":1572270063000},"page":"e1007867","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Cooperativity between the 3\u2019 untranslated region microRNA binding sites is critical for the virulence of eastern equine encephalitis virus"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7312-0260","authenticated-orcid":true,"given":"Derek W.","family":"Trobaugh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengqun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishank","family":"Bhalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3475-8966","authenticated-orcid":true,"given":"Christina L.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4506-7842","authenticated-orcid":true,"given":"William B.","family":"Klimstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"ppat.1007867.ref001","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1056\/NEJM199706263362604","article-title":"Clinical and neuroradiographic manifestations of eastern equine encephalitis","volume":"336","author":"RL Deresiewicz","year":"1997","journal-title":"N Engl J Med"},{"key":"ppat.1007867.ref002","doi-asserted-by":"crossref","first-page":"10634","DOI":"10.1128\/JVI.01323-08","article-title":"Eastern and Venezuelan equine encephalitis viruses differ in their ability to infect dendritic cells and macrophages: impact of altered cell tropism on pathogenesis","volume":"82","author":"CL Gardner","year":"2008","journal-title":"J Virol"},{"key":"ppat.1007867.ref003","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1182\/blood-2012-07-445999","article-title":"Mononuclear phagocyte miRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis","volume":"121","author":"A Mildner","year":"2013","journal-title":"Blood"},{"key":"ppat.1007867.ref004","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nature12869","article-title":"RNA viruses can hijack vertebrate microRNAs to suppress innate immunity","volume":"506","author":"DW Trobaugh","year":"2014","journal-title":"Nature"},{"key":"ppat.1007867.ref005","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: genomics, biogenesis, mechanism, and function","volume":"116","author":"DP Bartel","year":"2004","journal-title":"Cell"},{"key":"ppat.1007867.ref006","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1126\/science.1073827","article-title":"A microRNA in a multiple-turnover RNAi enzyme complex","volume":"297","author":"G Hutv\u00e1gner","year":"2002","journal-title":"Science"},{"key":"ppat.1007867.ref007","doi-asserted-by":"crossref","first-page":"9779","DOI":"10.1073\/pnas.1630797100","article-title":"MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms","volume":"100","author":"Y Zeng","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"ppat.1007867.ref008","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: Target Recognition and Regulatory Functions","volume":"136","author":"DP Bartel","year":"2009","journal-title":"Cell"},{"key":"ppat.1007867.ref009","doi-asserted-by":"crossref","first-page":"101","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"V Agarwal","year":"2015","journal-title":"Elife"},{"key":"ppat.1007867.ref010","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nature09267","article-title":"Mammalian microRNAs predominantly act to decrease target mRNA levels","volume":"466","author":"H Guo","year":"2010","journal-title":"Nature"},{"key":"ppat.1007867.ref011","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.molcel.2014.08.028","article-title":"mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues","volume":"56","author":"SW Eichhorn","year":"2014","journal-title":"Mol Cell"},{"key":"ppat.1007867.ref012","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1126\/science.1113329","article-title":"Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA","volume":"309","author":"CL Jopling","year":"2005","journal-title":"Science"},{"key":"ppat.1007867.ref013","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.chom.2016.02.007","article-title":"A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration","volume":"19","author":"TKH Scheel","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ppat.1007867.ref014","doi-asserted-by":"crossref","first-page":"8849","DOI":"10.1128\/JVI.00456-10","article-title":"Cellular microRNAs inhibit replication of the H1N1 influenza A virus in infected cells","volume":"84","author":"L Song","year":"2010","journal-title":"J Virol"},{"key":"ppat.1007867.ref015","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1177\/1535370215589051","article-title":"Human miR-3145 inhibits influenza A viruses replication by targeting and silencing viral PB1 gene","volume":"240","author":"K Khongnomnan","year":"2015","journal-title":"Exp Biol Med (Maywood)"},{"key":"ppat.1007867.ref016","doi-asserted-by":"crossref","first-page":"ra126","DOI":"10.1126\/scisignal.aab3183","article-title":"The microRNA miR-485 targets host and influenza virus transcripts to regulate antiviral immunity and restrict viral replication","volume":"8","author":"H Ingle","year":"2015","journal-title":"Sci Signal"},{"key":"ppat.1007867.ref017","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.1128\/JVI.02655-12","article-title":"Human microRNA hsa-miR-296-5p suppresses enterovirus 71 replication by targeting the viral genome","volume":"87","author":"Z Zheng","year":"2013","journal-title":"J Virol"},{"key":"ppat.1007867.ref018","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1159\/000348504","article-title":"MicroRNA-23b Inhibits Enterovirus 71 Replication through Downregulation of EV71 VPl Protein","volume":"56","author":"B-P Wen","year":"2013","journal-title":"Intervirology"},{"key":"ppat.1007867.ref019","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.molmed.2016.11.003","article-title":"MicroRNA Regulation of RNA Virus Replication and Pathogenesis","volume":"23","author":"DW Trobaugh","year":"2017","journal-title":"Trends Mol Med"},{"key":"ppat.1007867.ref020","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1073\/pnas.1112263109","article-title":"Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex","volume":"109","author":"T Shimakami","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"ppat.1007867.ref021","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nrg3462","article-title":"Argonaute proteins: functional insights and emerging roles","volume":"14","author":"G. Meister","year":"2013","journal-title":"Nat Rev Genet"},{"key":"ppat.1007867.ref022","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1128\/JVI.07125-11","article-title":"MicroRNA Targeting of Neurotropic Flavivirus: Effective Control of Virus Escape and Reversion to Neurovirulent Phenotype","volume":"86","author":"BL Heiss","year":"2012","journal-title":"J Virol"},{"key":"ppat.1007867.ref023","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.virol.2014.04.001","article-title":"Silencing of neurotropic flavivirus replication in the central nervous system by combining multiple microRNA target insertions in two distinct viral genome regions","volume":"456\u2013457","author":"NL Teterina","year":"2014","journal-title":"Virology"},{"key":"ppat.1007867.ref024","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1128\/JVI.02990-13","article-title":"Stable, high-level expression of reporter proteins from improved alphavirus expression vectors to track replication and dissemination during encephalitic and arthritogenic disease","volume":"88","author":"C Sun","year":"2014","journal-title":"J Virol"},{"key":"ppat.1007867.ref025","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.3201\/eid1612.100640","article-title":"Eastern Equine Encephalitis Virus in Mosquitoes and Their Role as Bridge Vectors","volume":"16","author":"PM Armstrong","year":"2010","journal-title":"Emerg Infect Dis"},{"key":"ppat.1007867.ref026","article-title":"MicroRNA expression profiles in avian haemopoietic cells","volume":"4","author":"Y Yao","year":"2013","journal-title":"Front Genet"},{"key":"ppat.1007867.ref027","doi-asserted-by":"crossref","first-page":"685","DOI":"10.4269\/ajtmh.14-0081","article-title":"Field investigations of winter transmission of eastern equine encephalitis virus in Florida","volume":"91","author":"AM Bingham","year":"2014","journal-title":"Am J Trop Med Hyg"},{"key":"ppat.1007867.ref028","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0092-8674(79)90057-6","article-title":"Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation","volume":"18","author":"H Beug","year":"1979","journal-title":"Cell"},{"key":"ppat.1007867.ref029","first-page":"153","article-title":"MicroRNA expression profiles in avian haemopoietic cells","volume":"4","author":"Y Yao","year":"2013","journal-title":"Front Genet"},{"key":"ppat.1007867.ref030","doi-asserted-by":"crossref","first-page":"e1007584","DOI":"10.1371\/journal.ppat.1007584","article-title":"Rational design of a live-attenuated eastern equine encephalitis virus vaccine through informed mutation of virulence determinants","volume":"15","author":"DW Trobaugh","year":"2019","journal-title":"PLoS Pathog"},{"key":"ppat.1007867.ref031","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nri3070","article-title":"Monocyte recruitment during infection and inflammation","volume":"11","author":"C Shi","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"ppat.1007867.ref032","doi-asserted-by":"crossref","first-page":"3791","DOI":"10.4049\/jimmunol.1602000","article-title":"Innate Control of Adaptive Immunity: Beyond the Three-Signal Paradigm","volume":"198","author":"A Jain","year":"2017","journal-title":"J Immunol"},{"key":"ppat.1007867.ref033","doi-asserted-by":"crossref","first-page":"16026","DOI":"10.1073\/pnas.1110617108","article-title":"Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence","volume":"108","author":"CL Gardner","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"ppat.1007867.ref034","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.virol.2009.05.030","article-title":"Type I interferon induction is correlated with attenuation of a South American eastern equine encephalitis virus strain in mice","volume":"390","author":"CL Gardner","year":"2009","journal-title":"Virology"},{"key":"ppat.1007867.ref035","doi-asserted-by":"crossref","first-page":"5997","DOI":"10.1073\/pnas.85.16.5997","article-title":"Western equine encephalitis virus is a recombinant virus","volume":"85","author":"CS Hahn","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"ppat.1007867.ref036","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1128\/JVI.71.1.613-623.1997","article-title":"Recombinational history and molecular evolution of western equine encephalomyelitis complex alphaviruses","volume":"71","author":"SC Weaver","year":"1997","journal-title":"J Virol"},{"key":"ppat.1007867.ref037","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1128\/IAI.24.3.642-646.1979","article-title":"Interaction of alphaviruses with human peripheral leukocytes: in vitro replication of Venezuelan equine encephalomyelitis virus in monocyte cultures","volume":"24","author":"NH Levitt","year":"1979","journal-title":"Infect Immun"},{"key":"ppat.1007867.ref038","doi-asserted-by":"crossref","first-page":"e1002465","DOI":"10.1371\/journal.ppat.1002465","article-title":"Replication in Cells of Hematopoietic Origin Is Necessary for Dengue Virus Dissemination","volume":"8","author":"AM Pham","year":"2012","journal-title":"PLoS Pathog"},{"key":"ppat.1007867.ref039","doi-asserted-by":"crossref","first-page":"12117","DOI":"10.1073\/pnas.1206039109","article-title":"Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses","volume":"109","author":"RA Langlois","year":"2012","journal-title":"Proc Nat Acad Sci"},{"key":"ppat.1007867.ref040","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/nbt.2666","article-title":"MicrorNA-based strategy to mitigate the risk of gain-of-function influenza studies","volume":"31","author":"RA Langlois","year":"2013","journal-title":"Nat Biotechnol"},{"key":"ppat.1007867.ref041","doi-asserted-by":"crossref","first-page":"R166","DOI":"10.1186\/gb-2007-8-8-r166","article-title":"The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression","volume":"8","author":"LS Hon","year":"2007","journal-title":"Genome Biol"},{"key":"ppat.1007867.ref042","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.molcel.2007.06.017","article-title":"MicroRNA targeting specificity in mammals: determinants beyond seed pairing","volume":"27","author":"A Grimson","year":"2007","journal-title":"Mol Cell"},{"key":"ppat.1007867.ref043","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ng1536","article-title":"Combinatorial microRNA target predictions","volume":"37","author":"A Krek","year":"2005","journal-title":"Nat Genet"},{"key":"ppat.1007867.ref044","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1093\/nar\/gkm133","article-title":"Distance constraints between microRNA target sites dictate efficacy and cooperativity","volume":"35","author":"P Saetrom","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ppat.1007867.ref045","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1126\/science.1108784","article-title":"A cellular microRNA mediates antiviral defense in human cells","volume":"308","author":"C-H Lecellier","year":"2005","journal-title":"Science"},{"key":"ppat.1007867.ref046","doi-asserted-by":"crossref","first-page":"5381","DOI":"10.1074\/jbc.M114.626325","article-title":"miR-28-3p Is a Cellular Restriction Factor That Inhibits Human T Cell Leukemia Virus, Type 1 (HTLV-1) Replication and Virus Infection","volume":"290","author":"XT Bai","year":"2015","journal-title":"J Biol Chem"},{"key":"ppat.1007867.ref047","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Most mammalian mRNAs are conserved targets of microRNAs","volume":"19","author":"RC Friedman","year":"2009","journal-title":"Genome Res"},{"key":"ppat.1007867.ref048","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.cell.2015.02.025","article-title":"Hepatitis C Virus RNA Functionally Sequesters miR-122","volume":"160","author":"JM Luna","year":"2015","journal-title":"Cell"},{"key":"ppat.1007867.ref049","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.virusres.2015.01.016","article-title":"The 5\u201dand 3\u201d ends of alphavirus RNAs\u2014Non-coding is not non-functional","volume":"206","author":"JL Hyde","year":"2015","journal-title":"Virus Res"},{"key":"ppat.1007867.ref050","doi-asserted-by":"crossref","first-page":"4920","DOI":"10.1128\/JVI.02514-07","article-title":"Structural and nonstructural protein genome regions of eastern equine encephalitis virus are determinants of interferon sensitivity and murine virulence","volume":"82","author":"PV Aguilar","year":"2008","journal-title":"J Virol"},{"key":"ppat.1007867.ref051","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1099\/vir.0.008656-0","article-title":"Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model","volume":"90","author":"CH Logue","year":"2009","journal-title":"J Gen Virol"},{"key":"ppat.1007867.ref052","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.virol.2016.06.005","article-title":"Host translation shutoff mediated by non-structural protein 2 is a critical factor in the antiviral state resistance of Venezuelan equine encephalitis virus","volume":"496","author":"N Bhalla","year":"2016","journal-title":"Virology"},{"key":"ppat.1007867.ref053","doi-asserted-by":"crossref","first-page":"e1005786","DOI":"10.1371\/journal.ppat.1005786","article-title":"The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells","volume":"12","author":"AM Watson","year":"2016","journal-title":"PLoS Pathog"},{"key":"ppat.1007867.ref054","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1186\/gb-2003-5-1-r1","article-title":"MicroRNA targets in Drosophila","volume":"5","author":"AJ Enright","year":"2003","journal-title":"Genome Biol"},{"key":"ppat.1007867.ref055","doi-asserted-by":"crossref","first-page":"e363","DOI":"10.1371\/journal.pbio.0020363","article-title":"Human MicroRNA targets","volume":"2","author":"B John","year":"2004","journal-title":"Plos Biol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1007867","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1007867","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T01:49:36Z","timestamp":1611625776000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1007867"}},"subtitle":[],"editor":[{"given":"Sonja","family":"Best","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,10,28]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1007867","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/649525","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,28]]}}}