December 2, 2002

Cell Surface Leukocyte Elastase in HIV Binding and Infectivity

Cynthia L Bristow, PhD

Center for Biomedical Research, Population Council, Rockefeller University campus

 HIV entry and infectivity are dependent on co-patching of the canonical HIV receptors with cell surface human leukocyte elastase (HLE) in response to ligation by a₁Proteinase Inhibitor (a₁antitrypsin, a₁PI).  Indeed, the increase in circulating a₁PI attendant to the acute phase of inflammation correlates with increased viral load in HIV infected individuals.  Exposure of cells to a₁PI initiates a sequence in which HIV co-receptors are initially disperse and are stimulated to co-patch within 15 min.  We have observed that when cells are exposed to a₁ PI for 60 min., virus is detected bound to small platelet-like transitory cytoplasmic bodies (SPTBalls).  We and others have shown that a variety of cells become resistant to HIV when cells are preconditioned with a₁PI for more than 60 min prior to exposure to HIV.  The corresponding disappearance of HIV infectivity and appearance of SPTBalls in vitro suggested co-patched receptors may pinch off providing a limited window of time for their concerted function, in this case HIV binding.  We show here that the appearance of CD4⁺ SPTBalls corresponds to the perceived disappearance of CD4⁺ cells in HIV infected individuals.