CCR5 is a functional receptor for the CC chemokines MIP-lft, MIP-Ш, RANTES, and MCP-2. It is
expressed in memory T cells, macrophages, dendritic cells, and microglia. CCR5 also constitutes the main coreceptor for the macrophage (M)-tropic strains of HIV-1 and HIV-2, that is responsible for disease transmission. A nonfunctional allele of the CCR5 gene (CCCR5A32), frequent in populations of European origin, provides marked resistance against HIV to homozygotes, and is associated with delayed AIDS progression of heterozygotes. Numerous other variant alleles of CCR5 have been described in human populations as well as in other mammalian species. The receptor constitutes a potential target for therapeutics to block HIV infection, and for various immune diseases such as rheumatoid arthritis, multiple sclerosis, and graft-versus-host disease. Chemokine variants, monoclonal antibodies, and small chemical inhibitors have been developed in this context.