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 conformational transitions of the HIV-1 envelope glycoproteins that contribute to virus entry are being characterized. The laboratory is devoted to understanding HIV-1 entry at the molecular level, and identifying and characterizing inhibitors. The interaction of small-molecule entry inhibitors and 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.
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