title: CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1.
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-1alpha, and MIP-1beta, 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.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
authors.forename: G
authors.initials: G
authors.lastname: Alkhatib
authors.forename: C
authors.initials: C
authors.lastname: Combadiere
authors.forename: C C
authors.initials: CC
authors.lastname: Broder
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: P E
authors.initials: PE
authors.lastname: Kennedy
authors.forename: P M
authors.initials: PM
authors.lastname: Murphy
authors.forename: E A
authors.initials: EA
authors.lastname: Berger
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015704:CD4 Antigens / Q000502:physiology; D002459:Cell Fusion; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism* / Q000494:pharmacology; D015686:Gene Products, env / Q000502:physiology; D015726:Giant Cells / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019402:Macrophage Inflammatory Proteins; D008264:Macrophages / Q000821:virology*; D008561:Membrane Fusion; D051379:Mice; D015846:Monokines / Q000378:metabolism / Q000494:pharmacology; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000502:physiology*; D015728:Receptors, HIV / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000821:virology; D014407:Tumor Cells, Cultured
chemical_list: D015704:CD4 Antigens; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D015686:Gene Products, env; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D011994:Recombinant Proteins