Major interests of the laboratory are human immunodeficiency virus entry and pathogenesis. Central to both of these processes are the viral envelope glycoproteins, which mediate the binding and fusion of the virus with the target cell and the cytopathic effects of infection. The laboratory is devoted to understanding how virus entry occurs at the molecular level and how neutralizing antibodies interfere with virus entry. Means of eliciting neutralizing antibodies with broader reactivity are being explored. The mechanisms of viral cytopathic effects and the contribution of these processes to CD4 lymphocyte depletion in vivo are being studied.
Another interest of the laboratory is the species-specific block to HIV-1 that operates after virus entry. A component of cytoplasmic bodies, TRIM5α, blocks HIV-1 in Old World monkey cells. Human TRIM5α also exhibits anti-HIV-1 activity, but this is less potent than the monkey orthologue. The mechanism of action and the role of species-specific and individual variation in TRIM5α in virus resistance are being explored.