CC CKR5: A RANTES, MIP-1α, MIP-1β Receptor as a Fusion Cofactor for Macrophage-Tropic HIV-1

TLDR

HIV‑1 entry into CD4⁺ cells requires fusion cofactors, such as the G‑protein–coupled receptor Fusin that supports T‑cell line–tropic isolates. The chemokine receptor CC CKR5 acts as a fusion cofactor for macrophage‑tropic HIV‑1, enabling CD4⁺ cells to fuse with these strains and is selectively expressed in susceptible cell types.

Abstract

Human immunodeficiency virus-type 1 (HIV-1) entry requires fusion cofactors on the CD4 + target cell. Fusin, a heterotrimeric GTP-binding protein (G protein)-coupled receptor, serves as a cofactor for T cell line-tropic isolates. The chemokines RANTES, MIP-1α, and MIP-1β, which suppress infection by macrophage-tropic isolates, selectively inhibited cell fusion mediated by the corresponding envelope glycoproteins (Envs). Recombinant CC CKR5, a G protein-coupled receptor for these chemokines, rendered CD4-expressing nonhuman cells fusion-competent preferentially with macrophage-tropic Envs. CC CKR5 messenger RNA was detected selectively in cell types susceptible to macrophage-tropic isolates. CC CKR5 is thus a fusion cofactor for macrophage-tropic HIV-1 strains.