Philip M. Murphy

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

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.

Viral Mimicry of Chemokines and Chemokine Receptors

The last few years have witnessed the convergence of what had previously been two oppositely directed research areas: the study of leukocyte migration and the study of microbial virulence factors (Table 1; 1–10). It is now clear that many of the factors involved in microbial virulence are members of the chemokine-signaling system (11–25), which is normally responsible for directing phagocytes and lymphocytes to sites of infection (1,7,26). In some cases, usage of chemokine-system components has actually been shown to be essential for the life cycle of the pathogen (20,24,25,27,28).