{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:39:18Z","timestamp":1791214758656,"version":"4.1.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"21","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Virus recognition and response by the innate immune system are critical components of host defense against infection. Activation of cell-intrinsic immunity and optimal priming of adaptive immunity against West Nile virus (WNV), an emerging vector-borne virus, depend on recognition by RIG-I and MDA5, two cytosolic pattern recognition receptors (PRRs) of the RIG-I-like receptor (RLR) protein family that recognize viral RNA and activate defense programs that suppress infection. We evaluated the individual functions of RIG-I and MDA5 both\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            in pathogen recognition and control of WNV. Lack of RIG-I or MDA5 alone results in decreased innate immune signaling and virus control in primary cells\n            <jats:italic>in vitro<\/jats:italic>\n            and increased mortality in mice. We also generated\n            <jats:italic>RIG-I<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            \u00d7\n            <jats:italic>MDA5<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            double-knockout mice and found that a lack of both RLRs results in a complete absence of innate immune gene induction in target cells of WNV infection and a severe pathogenesis during infection\n            <jats:italic>in vivo<\/jats:italic>\n            , similar to findings for animals lacking MAVS, the central adaptor molecule for RLR signaling. We also found that RNA products from WNV-infected cells but not incoming virion RNA display at least two distinct pathogen-associated molecular patterns (PAMPs) containing 5\u2032 triphosphate and double-stranded RNA that are temporally distributed and sensed by RIG-I and MDA5 during infection. Thus, RIG-I and MDA5 are essential PRRs that recognize distinct PAMPs that accumulate during WNV replication. Collectively, these experiments highlight the necessity and function of multiple related, cytoplasmic host sensors in orchestrating an effective immune response against an acute viral infection.\n          <\/jats:p>","DOI":"10.1128\/jvi.01488-13","type":"journal-article","created":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T04:00:07Z","timestamp":1377144007000},"page":"11416-11425","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":200,"title":["The Essential, Nonredundant Roles of RIG-I and MDA5 in Detecting and Controlling West Nile Virus Infection"],"prefix":"10.1128","volume":"87","author":[{"given":"John S.","family":"Errett","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul S.","family":"Suthar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory Vaccine Center at Yerkes, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee","family":"McMillan","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Michael","family":"Gale","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(02)00368-7"},{"key":"e_1_3_2_3_2","first-page":"1009","article-title":"West Nile virus disease and other arboviral diseases\u2014United States, 2010","volume":"60","author":"Centers for Disease Control and Prevention","year":"2011","unstructured":"Centers for Disease Control and Prevention. 2011. West Nile virus disease and other arboviral diseases\u2014United States, 2010. MMWR Morb. Mortal. Wkly. Rep. 60:1009\u20131013.","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"e_1_3_2_4_2","volume-title":"West Nile virus: final cumulative maps and data for 1999\u20132012","author":"Centers for Disease Control and Prevention","year":"2013","unstructured":"Centers for Disease Control and Prevention. 2013. West Nile virus: final cumulative maps and data for 1999\u20132012. Centers for Disease Control and Prevention, Atlanta, GA. http:\/\/www.cdc.gov\/westnile\/statsMaps\/cumMapsData.html."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2010.03438.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2012.02.018"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1108.050289a"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01122-06"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp048261"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02692-10"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2950"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00935-08"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01305-07"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.14.7737-7747.2004"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000757"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00489-06"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030106"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00918-08"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.21.13350-13361.2005"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042530"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.4.2578-2586.2003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.15.8312-8321.2004"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01650-06"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3108"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003168"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.003"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01080-07"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000607"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.6.2913-2923.2006"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003118"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04193"},{"key":"e_1_3_2_32_2","first-page":"17","article-title":"Induction of IRF-3 and IRF-7 phosphorylation following activation of the RIG-I pathway","volume":"52","author":"Paz S","year":"2006","unstructured":"PazSSunQNakhaeiPRomieu-MourezRGoubauDJulkunenILinRHiscottJ. 2006. 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