Role of HIV Envelope Proteins In Viral Replication and HIV Pathogenesis

National Institute Of Allergy And Infectious Diseases

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Abstract

In past years we have evaluated the impact of gp120 signaling through CD4 and CCR5 and have expanded these studies to include signaling through integrin a4b7. One of the main findings of these studies is that HIV envelope-mediated signaling can promote viral replication. This ability can play a particularly important role in viral replication in mucosal tissues, that occurs in the very early stages of HIV infection, when activated target cells are limited. In the past we demonstrated, in a non-human primate (NHP) model of HIV/SIV infection, that an antibody blocking gp120 interactions with integrin a4b7 prevents transmission in a rhesus macaque model of mucosal transmission. In our current work we are exploring the ways in which signaling through integrin a4b7, either by MAdCAM (its natural ligand) or gp120 induces a specific CD4+ T cells differentiation pattern. We are also exploring the role of MAdCAM and gp120 costimulation in the formation of persistent HIV reservoirs.