CCR5

CCR5 is a C-C chemokine receptor and a G protein-coupled receptor that plays a role in immune signaling. It is encoded by the CCR5 gene on chromosome 3 and is expressed on several immune cell types, including T cells, macrophages, and dendritic cells. Its presence helps coordinate immune cell movement in tissues.

CCR5 binds several CC chemokines, notably CCL3 (MIP-1α), CCL4 (MIP-1β), and CCL5 (RANTES). By transducing signals through G proteins, it guides leukocytes to sites of inflammation and participates in the regulation of immune responses.

In addition to its normal immune function, CCR5 acts as a coreceptor for entry of certain strains of HIV-1. R5-tropic HIV-1 viruses require CD4 and CCR5 to enter and infect host cells, whereas X4-tropic viruses use CXCR4. The availability of CCR5 on target cells influences viral tropism and infection efficiency.

A common loss-of-function variant, CCR5-Δ32, involves a 32-base-pair deletion that yields a nonfunctional receptor. Homozygotes for CCR5-Δ32 show strong resistance to mucosal HIV-1 infection, while heterozygotes may experience slower disease progression if infected. The allele is most frequent among individuals of Northern European descent, with varying frequencies worldwide.

Therapeutically, CCR5 is targeted by maraviroc, a small-molecule antagonist approved for treating CCR5-tropic HIV-1 infection. Other strategies include monoclonal antibodies such as leronlimab and gene-editing approaches aimed at disrupting CCR5 expression in immune cells, explored as potential avenues toward functional cures or improved HIV management. Because CCR5 participates in leukocyte trafficking and inflammation, it has also been investigated as a target in other inflammatory and autoimmune contexts.