{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:18:05Z","timestamp":1792466285595,"version":"4.5.0"},"reference-count":61,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,12,15]]},"abstract":"<jats:p>In humans, the elderly and immunocompromised are at greatest risk for disseminated West Nile virus (WNV) infection, yet the immunologic basis for this remains unclear. We demonstrated previously that B cells and IgG contributed to the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A. Marri, D. Mahan, and M. Engle. 2003. J. Virol. 77:2578\u20132586). In this paper, we addressed the function of IgM in controlling WNV infection. C57BL\/6J mice (sIgM\u2212\/\u2212) that were deficient in the production of secreted IgM but capable of expressing surface IgM and secreting other immunoglobulin isotypes were vulnerable to lethal infection, even after inoculation with low doses of WNV. Within 96 h, markedly higher levels of infectious virus were detected in the serum of sIgM\u2212\/\u2212 mice compared with wild-type mice. The enhanced viremia correlated with higher WNV burdens in the central nervous system, and was also associated with a blunted anti-WNV IgG response. Passive transfer of polyclonal anti-WNV IgM or IgG protected sIgM\u2212\/\u2212 mice against mortality, although administration of comparable amounts of a nonneutralizing monoclonal anti-WNV IgM provided no protection. In a prospective analysis, a low titer of anti-WNV IgM antibodies at day 4 uniformly predicted mortality in wild-type mice. Thus, the induction of a specific, neutralizing IgM response early in the course of WNV infection limits viremia and dissemination into the central nervous system, and protects against lethal infection.<\/jats:p>","DOI":"10.1084\/jem.20031223","type":"journal-article","created":{"date-parts":[[2003,12,9]],"date-time":"2003-12-09T01:33:53Z","timestamp":1070933633000},"page":"1853-1862","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":260,"title":["A Critical Role for Induced IgM in the Protection against West Nile Virus Infection"],"prefix":"10.1084","volume":"198","author":[{"given":"Michael S.","family":"Diamond","sequence":"first","affiliation":[{"name":"1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110"},{"name":"2Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110"},{"name":"3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Sitati","sequence":"additional","affiliation":[{"name":"2Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindzy D.","family":"Friend","sequence":"additional","affiliation":[{"name":"3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Higgs","sequence":"additional","affiliation":[{"name":"4Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bimmi","family":"Shrestha","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Engle","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2003,12,8]]},"reference":[{"key":"2023072822090301700_BIB1","doi-asserted-by":"crossref","first-page":"643","DOI":"10.3201\/eid0505.990505","volume":"5","year":"1999","journal-title":"Emerg. 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