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Pathogenesis of human retroviruses
The major interests of the laboratory are the early events in human immunodeficiency virus (HIV-1) infection. Understanding and blocking these early events are critical to interrupting HIV-1 transmission and changing the course of the global AIDS pandemic. The laboratory studies HIV-1 entry into cells, a process that is mediated by the viral envelope glycoproteins. These glycoproteins bind receptors on the target cell and fuse viral and cell membranes. The laboratory is devoted to understanding this process at the molecular level, and identifying and characterizing inhibitors. The interaction of neutralizing antibodies with the HIV-1 envelope glycoproteins is being studied.
In virus-producing cells, expression of the HIV-1 envelope glycoproteins results in cytopathic effects. These toxic effects result from the membrane-fusing activity of the HIV-1 envelope glycoproteins, which results in damage to the host cell membranes. The contribution of these processes to the depletion of CD4-positive T lymphocytes in vivo is being studied. The laboratory is also investigating the molecular events involved in the uncoating of the HIV-1 capsid following the entry of the virus into the host cell. In some mammalian species, tripartite motif (TRIM) proteins have evolved to recognize retroviral capsids and block virus infection. The molecular basis for this novel form of innate intracellular immunity is being pursued.
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