A TYROSINE-RICH REGION IN THE N-TERMINUS OF CCR5 IS IMPORTANT FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENTRY AND MEDIATES AN ASSOCIATION BETWEEN GP120 AND CCR5

Human immunodeficiency virus type 1 (HIV-1) requires the presence of s pecific chemokine receptors in addition to CD4 to enter target cells. The chemokine receptor CCR5 is used by the macrophage-tropic strains o f HIV-1 that predominate during the asymptomatic stages of infection. Here we identify a small tyrosine-rich region of CCR5 proximal to the N-terminal cysteine that is critical for entry of macrophage-tropic an d dual-tropic variants of HIV-1. HIV-1 infection of cells expressing C CR5 mutants with changes in this region was substantially reduced comp ared with the infection of cells bearing wild-type CCR5. Simian immuno deficiency virus (SIV(mac)239) entry was also ablated on a subset of t hese mutants hut enhanced on others. These differences in virus entry were correlated with the relative ability of soluble, monomeric HIV-1 and SIV(mac)239 gp120 glycoproteins to bind the CCR5 mutants. These re sults identify a region of CCR5 that is necessary for the physical ass ociation of the gp120 envelope glycoprotein with CCR5 and for HIV-1 in fection.