CHEMOKINE RECEPTORS AS FUSION COFACTORS FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)

CD4 is the primary cellular receptor for human immunodeficiency virus type 1 (HIV-I), but is not sufficient for entry of HIV-1 into cells, A fter a decade-long search, the cellular coreceptors that HIV-1 require s in conjunction with CD4 have been identified as members of the chemo kine receptor family of seven-transmembrane G-protein coupled receptor s. The discovery of distinct chemokine receptors that support entry of T-cell tropic (CXCR-4) and macrophage tropic HIV-1 strains (CCR-5) ex plains the differences in cell tropism between viral strains, the inab ility of HIV-1 to infect most nonprimate cells, and the resistance of a small percentage of the population to HIV-1 infection. Further under standing of the role of chemokine receptors in viral entry may also he lp explain the evolution of more pathogenic forms of the virus, viral transmission, and HIV-induced pathogenesis, These recent discoveries w ill aid the development of strategies for combating HIV-1 transmission and spread, the understanding of HIV-1 fusion mechanisms, and the pos sible development of small animal models for HIV-1 drug and vaccine te sting.