title: B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus.
abstract: 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 (microMT mice) developed increased CNS viral burdens and were vulnerable to lethal infection at low doses of virus. Notably, an approximately 500-fold difference in serum viral load was detected in micro MT 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 micro MT 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.
authors.affiliation: Department of Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. diamond@borcim.wustl.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Bimmi
authors.initials: B
authors.lastname: Shrestha
authors.forename: Anantha
authors.initials: A
authors.lastname: Marri
authors.forename: Darby
authors.initials: D
authors.lastname: Mahan
authors.forename: Michael
authors.initials: M
authors.lastname: Engle
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001921:Brain / Q000821:virology; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000276:immunology* / Q000821:virology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008198:Lymph Nodes / Q000821:virology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D013154:Spleen / Q000821:virology; D014766:Viremia / Q000276:immunology / Q000821:virology; D014901:West Nile Fever / Q000276:immunology* / Q000821:virology; D014902:West Nile virus / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000914:Antibodies, Viral; D007106:Immune Sera; D007074:Immunoglobulin G; D007075:Immunoglobulin M