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Journal of Virology, June 2005, p. 7466-7477, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7466-7477.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection

Erin Mehlhop,3,{dagger} Kevin Whitby,1,{dagger} Theodore Oliphant,2 Anantha Marri,1 Michael Engle,1 and Michael S. Diamond1,2,3*

Departments of Medicine,1 Molecular Microbiology,2 Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri 631103

Received 15 December 2004/ Accepted 15 February 2005

Infection with West Nile virus (WNV) causes a severe infection of the central nervous system (CNS) with higher levels of morbidity and mortality in the elderly and the immunocompromised. Experiments with mice have begun to define how the innate and adaptive immune responses function to limit infection. Here, we demonstrate that the complement system, a major component of innate immunity, controls WNV infection in vitro primarily in an antibody-dependent manner by neutralizing virus particles in solution and lysing WNV-infected cells. More decisively, mice that genetically lack the third component of complement or complement receptor 1 (CR1) and CR2 developed increased CNS virus burdens and were vulnerable to lethal infection at a low dose of WNV. Both C3-deficient and CR1- and CR2-deficient mice also had significant deficits in their humoral responses after infection with markedly reduced levels of specific anti-WNV immunoglobulin M (IgM) and IgG. Overall, these results suggest that complement controls WNV infection, in part through its ability to induce a protective antibody response.

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

{dagger} These authors contributed equally to the work.

Journal of Virology, June 2005, p. 7466-7477, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7466-7477.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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