THE ABILITY OF HIV TYPE-1 TO USE CCR-3 AS A CORECEPTOR IS CONTROLLED BY ENVELOPE V1 V2 SEQUENCES ACTING IN CONJUNCTION WITH A CCR-5 TROPIC V3 LOOP/

Although infection by primary HIV type 1 (HIV-1) isolates normally req uires the functional interaction of the viral envelope protein with bo th CD4 and the CCR-5 coreceptor, a subset of such isolates also are ab le to use the distinct CCR-3 receptor. By analyzing the ability of a s eries of wild-type and chimeric HIV-1 envelope proteins to mediate CCR -3-dependent infection, we have determined that CCR-3 tropism maps to the V1 and V2 variable region of en,elope. Although substitution of th e V1/V2 region of a CCR-3 tropic envelope into the contest of a CCR-5 tropic envelope is both necessary and sufficient to confer CCR-3 tropi sm, this same substitution has no phenotypic effect when inserted into a CXCR-4 tropic HIV-1 envelope contest. However, this latter chimera acquires both CCR-3 and CCR-5 tropism when a CCR-5 tropic V3 loop sequ ence also is introduced. These data demonstrate that the V1/2 region o f envelope can, like the V3 loop region, encode a particular corecepto r requirement and suggest that a functional envelope:CCR-3 interaction may depend on the cooperative interaction of CCR-3 with both the V1/V 2 and the V3 region of envelope.