STRUCTURAL INTERACTIONS BETWEEN CHEMOKINE RECEPTORS, GP120 ENV AND CD4

Seven transmembrane segment (7TMS) receptors for chemokines and relate d molecules have been demonstrated to be essential, in addition to CD4 , for HIV and SIV infection. The beta-chemokine receptor CCR5 is the p rimary, perhaps sole, co-receptor for HIV-1 during the early and chron ic phases of infection and supports infection by most primary HIV-1 an d many SN isolates. Late-stage primary and laboratory-adapted HIV-1, H IV-2, and SIV isolates can use other 7TMS receptors. CXCR4 appears esp ecially important in late-stage HN infection; several related receptor s can also be used. The specificity of SIV viruses is similar. Commona lities among these receptors, combined with analyses of mutated molecu les, indicate that discrete, conformationally-dependent sites on the c hemokine receptors determine their association with the third variable and conserved regions of viral envelope glycoproteins. These studies are useful for elucidating the mechanism and molecular determinants of HIV-1 entry, and of inhibitors to that entry.