Chemokine receptors in HIV-1 and SIV infection

Seven transmembrane segment (7TMS) receptors for chemokines and related mol ecules have been demonstrated to be essential, in addition to CD4, for HIV and SIV infection. The beta-chemokine receptor CCR5 is the primary, perhaps sole, coreceptor for HIV-1: during the early and chronic phases of infecti on, and supports infection by most primary HIV-1 and many SIV isolates. Lat e-stage primary and laboratory-adapted HIV-1, HIV-2, and SIV isolates can u se other 7TMS receptors. CXCR4 appears especially important in late-stage H IV infection; several related receptors can also be used. The specificity o f SIV viruses is similar. Commonalities among these receptors, combined wit h analyses of mutated molecules, indicate that discrete, conformationally-d ependent sites on the chemokine receptors determine their association with the third variable and conserved regions of viral envelope glycoproteins. T hese studies are useful for elucidating the mechanism and molecular determi nants of HIV-1 entry, and of inhibitors to that entry.