{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:42:35Z","timestamp":1791286955954,"version":"4.1.0"},"reference-count":76,"publisher":"American Society for Microbiology","issue":"24","license":[{"start":{"date-parts":[[2006,12,15]],"date-time":"2006-12-15T00:00:00Z","timestamp":1166140800000},"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":[[2006,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Although studies have established that innate and adaptive immune responses are important in controlling West Nile virus (WNV) infection, the function of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes in modulating viral pathogenesis is less well characterized. Using a mouse model, we examined the role of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in coordinating protection against WNV infection. A genetic or acquired deficiency of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells resulted in a protracted WNV infection in the central nervous system (CNS) that culminated in uniform lethality by 50 days after infection. Mice surviving past day 10 had high-level persistent WNV infection in the CNS compared to wild-type mice, even 45 days following infection. The absence of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell help did not affect the kinetics of WNV infection in the spleen and serum, suggesting a role for CD4-independent clearance mechanisms in peripheral tissues. WNV-specific immunoglobulin M (IgM) levels were similar to those of wild-type mice in CD4-deficient mice early during infection but dropped \u223c20-fold at day 15 postinfection, whereas IgG levels in CD4-deficient mice were \u223c100- to 1,000-fold lower than in wild-type mice throughout the course of infection. WNV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell activation and trafficking to the CNS were unaffected by the absence of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells at day 9 postinfection but were markedly compromised at day 15. Our experiments suggest that the dominant protective role of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells during primary WNV infection is to provide help for antibody responses and sustain WNV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses in the CNS that enable viral clearance.\n                  <\/jats:p>","DOI":"10.1128\/jvi.01650-06","type":"journal-article","created":{"date-parts":[[2006,11,27]],"date-time":"2006-11-27T18:43:39Z","timestamp":1164653019000},"page":"12060-12069","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":188,"title":["CD4\n                    <sup>+<\/sup>\n                    T-Cell Responses Are Required for Clearance of West Nile Virus from the Central Nervous System"],"prefix":"10.1128","volume":"80","author":[{"given":"Elizabeth M.","family":"Sitati","sequence":"first","affiliation":[{"name":"Departments of Molecular Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Departments of Molecular Microbiology"},{"name":"Medicine"},{"name":"Pathology &amp; Immunology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.10.8032-8036.1998"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324717"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.23.12388-12393.2002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.1406"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2004.02.004"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(02)00368-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04651"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.4.2578-2586.2003"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031223"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-1229(05)80011-X"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0704.017408"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.24.12941-12949.2003"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0898-945"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90462-8"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.5.3623-3629.1999"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042530"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051970"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)01128-4"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8648"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.002221"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1910207"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1108.050289a"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(01)01477-0"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1988.tb00732.x"},{"key":"e_1_3_2_26_2","unstructured":"Janeway C. 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