EXPRESSION CLONING OF NEW RECEPTORS USED BY SIMIAN AND HUMAN IMMUNODEFICIENCY VIRUSES

Several members of the chemokine-receptor family serve, in conjunction with CD4, as receptors for the entry of human immunodeficiency virus type I (HIV-1) into cells(1-6). The principal receptor for entry of ma crophage-tropic (M-tropic) HIV-1 strains is CCR5, whereas that for T-c ell-line-tropic (T-tropic) strains is CXCR4. Unlike HlV-1, infection w ith either M-tropic or T-tropic strains of simian immunodeficiency vir us (SIV) can be mediated by CCR5, but not CXCR4 (refs 7-10). SIV strai ns will also infect CD4(+) cells that lack CCR5, which suggests that t hese strains use as yet unidentified receptors(7,9,10). Here we use an expression-cloning strategy to identify SIV receptors and have isolat ed genes encoding two members of the seven-transmembrane G-protein-cou pled receptor family that are used not only by SIVs, but also by strai ns of HIV-2 and M-tropic HIV-1. Both receptors are closely related to the chemokine-receptor family and are expressed in lymphoid tissues. O ne of the receptors is also expressed in colon and may therefore be im portant in viral transmission. Usage of these new receptors following experimental infection of non-human primates with SIV strains may prov ide important insight into viral transmission and the mechanisms of SI V- and HIV-induced acquired immune-deficiency syndrome.