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Journal of Virology, February 2003, p. 2578-2586, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2578-2586.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

B Cells and Antibody Play Critical Roles in the Immediate Defense of Disseminated Infection by West Nile Encephalitis Virus

Michael S. Diamond,* Bimmi Shrestha, Anantha Marri, Darby Mahan, and Michael Engle

Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri

Received 12 September 2002/ Accepted 20 November 2002

West Nile virus (WNV) causes severe central nervous system (CNS) infection primarily in humans who are immunocompromised or elderly. In this study, we addressed the mechanism by which the immune system limits dissemination of WNV infection by infecting wild-type and immunodeficient inbred C57BL/6J mice with a low-passage WNV isolate from the recent epidemic in New York state. Wild-type mice replicated virus extraneuronally in the draining lymph nodes and spleen during the first 4 days of infection. Subsequently, virus spread to the spinal cord and the brain at virtually the same time. Congenic mice that were genetically deficient in B cells and antibody (µMT mice) developed increased CNS viral burdens and were vulnerable to lethal infection at low doses of virus. Notably, a ~500-fold difference in serum viral load was detected in µMT mice as early as 4 days after infection, a point in the infection when low levels of neutralizing immunoglobulin M antibody were detected in wild-type mice. Passive transfer of heat-inactivated serum from infected and immune wild-type mice protected µMT mice against morbidity and mortality. We conclude that antibodies and B cells play a critical early role in the defense against disseminated infection by WNV.

* Corresponding author. Mailing address: Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, Washington University School Of Medicine, 660 S. Euclid Ave., Box 8051, St. Louis, MO 63110. Phone: (314) 362-2842. Fax: (314) 362-9230. E-mail: diamond{at}borcim.wustl.edu.

Journal of Virology, February 2003, p. 2578-2586, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2578-2586.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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