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 requires the functional interaction of the viral envelope protein with both CD4 and the CCR-5 coreceptor, a subset of such isolates also are able to use the distinct CCR-3 receptor. By analyzing the ability of a series 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 envelope. Although substitution of the V1/V2 region of a CCR-3 tropic envelope into the context of a CCR-5 tropic envelope is both necessary and sufficient to confer CCR-3 tropism, this same substitution has no phenotypic effect when inserted into a CXCR-4 tropic HIV-1 envelope context. However, this latter chimera acquires both CCR-3 and CCR-5 tropism when a CCR-5 tropic V3 loop sequence also is introduced. These data demonstrate that the V1/2 region of envelope can, like the V3 loop region, encode a particular coreceptor requirement and suggest that a functional envelope:CCR-3 interaction may depend on the cooperative interaction of CCR-3 with both the V1/V2 and the V3 region of envelope.
Ross
T M
TM
Department of Genetics, Duke University Medical Center, Box 3025, Durham, NC 27710, USA.
Cullen
B R
BR
D000818:Animals; D019556:COS Cells; D002459:Cell Fusion; D003001:Cloning, Molecular; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1; D010446:Peptide Fragments / Q000378:metabolism*; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
D015699:HIV Envelope Protein gp120; C059761:HIV envelope protein gp120 (135-148); C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins