Chemokine receptor type 5 (CCR5)

Chemokine receptor type 5 (CCR5) is a G protein-coupled receptor primarily expressed on the surface of T lymphocytes, macrophages, dendritic cells, and other immune cells[2][5]. It mediates immune cell migration in response to chemokine ligands and is a key co-receptor for entry of R5-tropic HIV-1 strains into host cells by facilitating fusion of the viral and cellular membranes[2][4][5]. CCR5 has a well-characterized role in HIV/AIDS pathogenesis, as well as regulation of immune responses and inflammation. Drugs such as maraviroc bind allosterically to CCR5, inhibiting its interaction with both endogenous chemokines and HIV-1 gp120, thereby preventing viral entry and replication in CD4+ cells[1][2][4][5][6][7][8]. The use of CCR5 antagonists is clinically guided by HIV tropism assays, as only R5-tropic viruses are susceptible to this mechanism. Although generally well tolerated, CCR5 inhibitors may present specific safety risks, including potential immunological effects due to blockade of physiological chemokine signaling, risk of hepatotoxicity, and emergence of resistance in patients with non–R5-tropic HIV[4][5].

Other names

C-C chemokine receptor type 5CCR-5CD195

Allosteric antagonist (Maraviroc binds to a cavity in the transmembrane region of CCR5, stabilizing it in an inactive conformation and preventing HIV-1 gp120 from interacting with CCR5); Entry inhibitor (prevents HIV-1 from entering CD4+ T cells by blocking viral envelope–CCR5 interaction)