New Scholar Award in Global Infectious Disease
Michael S. Diamond, M.D., Ph.D.
Washington University School of Medicine

The Immunology and Neurobiology of West Nile Encephalitis in a Mouse Model of Disease

The research in our laboratory focuses on the interface between viral infection and the host immune response. Two globally important mosquito-borne human pathogens are studied, the West Nile encephalitis and dengue hemorrhagic fever viruses.

Studies with West Nile virus virus (WNV) focus on understanding the pathogenesis of infection, the mechanism by which the immune system limits dissemination into the central nervous system, and the nature of cell injury in neurons. A mouse model of infection has been established to determine how viral infection transitions from extraneural sites to the brain. Genetic deficiencies in several immune system mediators have been identified that result in severe disease phenotypes. Finally, to determine the mechanisms of cell injury in the brain, a cell culture model of WNV infection has been established in primary neuronal cells.  

Studies with dengue virus (DV) have focused on identifying the host and viral factors that modulate the severity of an infection. Interferons (IFN) inhibit DV infection by blocking the translation of viral RNA that occurs prior to RNA replication. Mutant DV strains have now been isolated that are resistant to IFN. Site-specific substitutions are underway to define the region(s) that confer resistance to IFN and the inhibitory molecules in the IFN antiviral pathway that block viral infection.

Contact Dr. Diamond.