Science · 1996 · 2.7K citations · 24 references
Life SciencesImmunologyInfectious DiseasesMolecular ImmunologyMolecular VirologyVirologyAntiviral ImmunityChemokine NetworksChemokine SignalingCytokine BiologyMacrophage BiologyViral TropismCd4 Positive T CellsCell Entry Fusion MechanismsEntry CofactorsG Protein-coupled Chemokine ReceptorsHeterotrimeric G Protein SignalingHiv Envelope Glycoprotein AntigensInflammatory ChemokinesViral Envelope Glycoproteins
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.
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.
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Thomas R. Fuerst, Edward G. Niles, F. William Studier et al. · Proceedings of the National Academy of Sciences · 1986 · 2.1K citations · Full text