{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:54:15Z","timestamp":1789901655401,"version":"4.0.1"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"16","license":[{"start":{"date-parts":[[2016,8,15]],"date-time":"2016-08-15T00:00:00Z","timestamp":1471219200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI083019"],"award-info":[{"award-number":["AI083019"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI074973"],"award-info":[{"award-number":["AI074973"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["5U54AI057160"],"award-info":[{"award-number":["5U54AI057160"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    West Nile virus (WNV) is the most important cause of epidemic encephalitis in North America. Innate immune responses, which are critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors, RIG-I and MDA5, and their downstream adaptor molecule, MAVS. Here, we show that a deficiency of MAVS in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In\n                    <jats:italic>Mavs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were polyfunctional and lysed peptide-pulsed target cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    . However, virus-specific T cells in the brains of infected\n                    <jats:italic>Mavs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibited lower functional avidity than those in wild-type animals, and even virus-specific memory T cells generated by prior immunization could not protect\n                    <jats:italic>Mavs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice from WNV-induced lethal disease. Concomitant with ineffective virus clearance, macrophage numbers were increased in the\n                    <jats:italic>Mavs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    brain, and both macrophages and microglia exhibited an activated phenotype. Microarray analyses of leukocytes in the infected\n                    <jats:italic>Mavs<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    brain showed a preferential expression of genes associated with activation and inflammation. Together, these results demonstrate a critical role for MAVS in hematopoietic cells in augmenting the kinetics of WNV clearance and thereby preventing a dysregulated and pathogenic immune response.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    West Nile virus (WNV) is the most important cause of mosquito-transmitted encephalitis in the United States. The innate immune response is known to be critical for protection in infected mice. Here, we show that expression of MAVS, a key adaptor molecule in the RIG-I-like receptor RNA-sensing pathway, in hematopoietic cells is critical for protection from lethal WNV infection. In the absence of MAVS, there is a massive infiltration of myeloid cells and virus-specific T cells into the brain and overexuberant production of proinflammatory cytokines. These results demonstrate the important role that MAVS expression in hematopoietic cells has in regulating the inflammatory response in the WNV-infected brain.\n                  <\/jats:p>","DOI":"10.1128\/jvi.00707-16","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T23:35:22Z","timestamp":1464219322000},"page":"7098-7108","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis"],"prefix":"10.1128","volume":"90","author":[{"given":"Jincun","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"},{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Vijay","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa, 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"}]},{"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Pathology and Immunology, and Molecular Microbiology, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Perlman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004530"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2950"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000757"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003118"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01488-13"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01026-10"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.04.010"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060792"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc15d03s31"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000636"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01049-10"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.12.8127-8131.1995"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737192"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.12.8568"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003292"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1257"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.24.13323-13334.2003"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39387"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903918"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1140"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00935-08"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12862"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-45"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-8"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199606000-00001"},{"key":"e_1_3_3_27_2","first-page":"623","article-title":"CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler's murine encephalomyelitis virus-induced demyelinating disease","volume":"9","author":"Bennett JL","year":"2003","unstructured":"Bennett JL, Elhofy A, Canto MC, Tani M, Ransohoff RM, Karpus WJ. 2003. CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler's murine encephalomyelitis virus-induced demyelinating disease. 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