{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T04:59:02Z","timestamp":1776488342446,"version":"3.51.2"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>West Nile virus (WNV) is a neurotropic ssRNA flavivirus that can cause encephalitis, meningitis, and death in humans and mice. Human TLR7 and TLR8 and mouse TLR7 recognize viral ssRNA motifs and induce antiviral immunity. However, the role of mouse TLR8 in antiviral immunity is poorly understood. In this article, we report that TLR8-deficient (Tlr8\u2212\/\u2212) mice were resistant to WNV infection compared with wild-type controls. Efficient WNV clearance and moderate susceptibility to WNV-mediated neuronal death in Tlr8\u2212\/\u2212 mice were attributed to overexpression of Tlr7 and IFN-stimulated gene-56 expression, whereas reduced expression of the proapoptotic gene coding Bcl2-associated X protein was observed. Interestingly, suppressor of cytokine signaling (SOCS)-1 directly associated with TLR8, but not with TLR7, indicating a novel role for TLR8 regulation of SOCS-1 function, whereas selective small interfering RNA knockdown of Socs-1 resulted in induced IFN-stimulated gene-56 and Tlr7 expression following WNV infection. Collectively, we report that TLR8 coupling with SOCS-1 inhibits TLR7-mediated antiviral immunity during WNV infection in mice.<\/jats:p>","DOI":"10.4049\/jimmunol.1600902","type":"journal-article","created":{"date-parts":[[2016,10,21]],"date-time":"2016-10-21T23:40:58Z","timestamp":1477093258000},"page":"4425-4435","source":"Crossref","is-referenced-by-count":29,"title":["TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1657-3618","authenticated-orcid":false,"given":"Amber M","family":"Paul","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, The University of Southern Mississippi , Hattiesburg, MS 39406"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhiraj","family":"Acharya","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Southern Mississippi , Hattiesburg, MS 39406"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3077-8748","authenticated-orcid":false,"given":"Linda","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Southern Mississippi , Hattiesburg, MS 39406"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Department of Microbiology and Immunology, School of Medicine, New York Medical College , Valhalla, NY 10595"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1891-5730","authenticated-orcid":false,"given":"Dobrivoje S","family":"Stokic","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Neurological Recovery, Methodist Rehabilitation Center , Jackson, MS 39216"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Arturo","family":"Leis","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Neurological Recovery, Methodist Rehabilitation Center , Jackson, MS 39216"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-697X","authenticated-orcid":false,"given":"Lena","family":"Alexopoulou","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Aix Marseille Universit\u00e9 UM2, INSERM, U1104, CNRS UMR7280 , 13288 Marseille,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terrence","family":"Town","sequence":"additional","affiliation":[{"name":"Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California , Los Angeles, CA 90033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-0778","authenticated-orcid":false,"given":"Richard A","family":"Flavell","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Howard Hughes Medical Institute , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erol","family":"Fikrig","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Howard Hughes Medical Institute , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengwei","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Southern Mississippi , Hattiesburg, MS 39406"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,12,1]]},"reference":[{"key":"2025030618355754700_r1","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.3390\/v5092079","article-title":"Ecology of West Nile virus in North America","volume":"5","author":"Reisen","year":"2013","journal-title":"Viruses"},{"key":"2025030618355754700_r2","doi-asserted-by":"crossref","first-page":"811","DOI":"10.3390\/v3060811","article-title":"West Nile virus: immunity and pathogenesis","volume":"3","author":"Lim","year":"2011","journal-title":"Viruses"},{"key":"2025030618355754700_r3","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1038\/nm1140","article-title":"Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis","volume":"10","author":"Wang","year":"2004","journal-title":"Nat. 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