The research in my laboratory focuses on the interface between viral pathogenesis and the host immune response. Two globally important mosquito-borne human pathogens are studied, the West Nile encephalitis and Dengue hemorrhagic fever viruses. They are single-stranded positive-polarity RNA viruses, and closely related to the viruses that cause yellow fever, St. Louis and Japanese encephalitis, and hepatitis C. Studies with West Nile and Dengue viruses have focused on investigating their pathogenesis and the immune system response that controls infection. Using in vitro models of infection in primary neurons, we are studying the mechanisms by which West Nile virus causes direct injury to different populations of neurons. Using a mouse model we have defined critical roles for interferon, antibody, complement, CD4⁺, and CD8⁺ cell in the control and eradication of West Nile virus infection. More recently, we have begun to study the structural basis of antibody-mediated neutralization of West Nile and Dengue virus. By combining our structural and pathogenesis data, we have developed and humanized a monoclonal antibody that has strong therapeutic activity against WNV even after the virus has disseminated into the central nervous system. This data is also being applied to the development of novel strategies for vaccine development.