SELECTIVE EMPLOYMENT OF CHEMOKINE RECEPTORS AS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 CORECEPTORS DETERMINED BY INDIVIDUAL AMINO-ACIDS WITHIN THE ENVELOPE V3 LOOP

The chemokine receptor CCR5 acts as an essential cofactor for cell ent ry by macrophage-tropic human immunodeficiency virus type 1 (HIV-1) st rains, whereas CXCR4 acts as an essential cofactor for T-cell-line-ada pted strains. We demonstrated that the specific amino acids in the V3 loop of the HIV-1 envelope protein that determine cellular tropism als o regulate chemokine coreceptor preference for cell entry by the virus . Further, a strong correlation was found between HIV-1 strains classi fied as syncytium inducing in standard assays and those using CXCR4 as a coreceptor. These data support the hypothesis that progressive adap tation to additional coreceptors is a key molecular basis for HIV-1 ph enotypic evolution in vivo.