HIV AND THE 7-TRANSMEMBRANE DOMAIN RECEPTORS

The recent discovery of a chemokine receptor, fusin (fusin/CXCR-4), as the long-sought human immunodeficiency virus type 1 (HIV-1) corecepto r opened an entirely new field of aquired immunodeficiency syndrome (A IDS) research on mechanisms of viral entry, tropism and pathogenesis. It was soon followed by the identification of the chemokine receptor C CR-5 as the major macrophage-tropic (M-tropic) HIV-1 coreceptor and th e demonstration that other chemokine receptors, CCR-3 and CCR-2b, also may serve as coreceptors, albeit at somewhat lower efficiency. Very r ecently it was demonstrated that the mechanism of the coreceptor funct ion involves the formation of a complex on the cell surface between th e HIV-1 envelope, the primary receptor CD4 and the coreceptor. Thus th e prevention of the HIV-1 envelope glycoprotein-mediated fusion by the chemokines RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alp ha) and MIP-1 beta, as well as by the recently identified fusin/CXCR-4 ligand, stromal cell-derived factor-1 (SDF-1) could be explained by d isruption of that complex. Interestingly, the identification of the HI V-1 coreceptor CCR-5 not only provided new insights into the mechanism s of viral entry and tropism, but also may help in explaining why some people with genetic alterations in CCR-5 are protected from HIV-1 inf ection.