THE RHESUS MACAQUE CCR3 CHEMOKINE RECEPTOR IS A CELL ENTRY COFACTOR FOR HIV-2, BUT NOT FOR HIV-1

The eotaxin receptor (CCR3) is a CD4-associated coreceptor for human i mmunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). By comparison with other chemokine receptors, such as CCR5 and CXCR4, the primary s equences of human CCR3 and its rhesus macaque homolog were markedly di fferent in their extracellular domains. Human CD4(+) cells expressing CCR3 from either human or macaque origin could be infected by HIV-2, w ith apparently similar efficiency, but only cells expressing human CCR 3 could be infected by HIV-1. It suggests that HIV-1 and HIV-2 envelop e proteins interact differently with the CCR3 coreceptor. HIV-I could infect cells expressing chimeric human/macaque CCR3 bearing either the first and second, or the third and fourth extracellular domains of hu man CCR3. As previously observed for CCR5, there seems to be a certain functional redundancy between domains supporting the coreceptor activ ity of CCR3. In spite of their close genetic relationship to HIV-2, tw o macaque simian immunodeficiency virus strains were apparently unable to use the CCR3 coreceptor from either human or simian origin. (C) 19 98 Academic Press.