REGIONS IN BETA-CHEMOKINE RECEPTORS CCR5 AND CCR2B THAT DETERMINE HIV-1 COFACTOR SPECIFICITY

Macrophage-tropic (M-tropic) HIV-1 strains use the beta-chemokine rece ptor CCR5, but not CCR2b, as a cofactor for membrane fusion and infect ion, while the dual-tropic strain 89.6 uses both. CCR5/2b chimeras and mutants were used to map regions of CCR5 important for cofactor funct ion and specificity. M-tropic strains required either the amino-termin al domain or the first extracellular loop of CCR5. A CCR2b chimera con taining the first 20 N-terminal residues of CCR5 supported M-tropic en velope protein fusion. Aminoterminal truncations of CCR5/CCR2b chimera s indicated that residues 2-5 are important for M-tropic viruses, whil e 89.6 is dependent on residues 6-9. The identification of multiple fu nctionally important regions in CCR5, coupled with differences in how CCR5 is used by M- and dual-tropic viruses, suggests that interactions between HIV-1 and entry cofactors are conformationally complex.