{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:43:26Z","timestamp":1791287006158,"version":"4.1.0"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"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":[[2006,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            West Nile virus (WNV) causes a severe central nervous system (CNS) infection in humans, primarily in the elderly and immunocompromised. Prior studies have established an essential protective role of several innate immune response elements, including alpha\/beta interferon (IFN-\u03b1\/\u03b2), immunoglobulin M, \u03b3\u03b4 T cells, and complement against WNV infection. In this study, we demonstrate that a lack of IFN-\u03b3 production or signaling results in increased vulnerability to lethal WNV infection by a subcutaneous route in mice, with a rise in mortality from 30% (wild-type mice) to 90% (IFN-\u03b3\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            or IFN-\u03b3R\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice) and a decrease in the average survival time. This survival pattern in IFN-\u03b3\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            and IFN-\u03b3R\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice correlated with higher viremia and greater viral replication in lymphoid tissues. The increase in peripheral infection led to early CNS seeding since infectious WNV was detected several days earlier in the brains and spinal cords of IFN-\u03b3\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            or IFN-\u03b3R\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice. Bone marrow reconstitution experiments showed that \u03b3\u03b4 T cells require IFN-\u03b3 to limit dissemination by WNV. Moreover, treatment of primary dendritic cells with IFN-\u03b3 reduced WNV production by 130-fold. Collectively, our experiments suggest that the dominant protective role of IFN-\u03b3 against WNV is antiviral in nature, occurs in peripheral lymphoid tissues, and prevents viral dissemination to the CNS.\n          <\/jats:p>","DOI":"10.1128\/jvi.00274-06","type":"journal-article","created":{"date-parts":[[2006,5,12]],"date-time":"2006-05-12T18:27:37Z","timestamp":1147458457000},"page":"5338-5348","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":174,"title":["Gamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection"],"prefix":"10.1128","volume":"80","author":[{"given":"Bimmi","family":"Shrestha","sequence":"first","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Wang","sequence":"additional","affiliation":[{"name":"Sections of Rheumatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie A.","family":"Samuel","sequence":"additional","affiliation":[{"name":"Molecular Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Whitby","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Craft","sequence":"additional","affiliation":[{"name":"Sections of Rheumatology"},{"name":"Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erol","family":"Fikrig","sequence":"additional","affiliation":[{"name":"Sections of Rheumatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Molecular Microbiology"},{"name":"Pathology and Immunology, 660 S. 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