PMID:8906795

Citation	Wu, L, Gerard, NP, Wyatt, R, Choe, H, Parolin, C, Ruffing, N, Borsetti, A, Cardoso, AA, Desjardin, E, Newman, W, Gerard, C and Sodroski, J (1996) CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature 384:179-83
Abstract	For efficient entry into target cells, primary macrophage-tropic and laboratory-adapted human immunodeficiency viruses type 1 (HIV-1) require particular chemokine receptors, CCR-5 and CXCR-4, respectively, as well as the primary receptor CD4 (refs 1-6). Here we show that a complex of gp120, the exterior envelope glycoprotein, of macrophage-tropic primary HIV-1 and soluble CD4 interacts specifically with CCR-5 and inhibits the binding of the natural CCR-5 ligands, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta (refs 7, 8). The apparent affinity of the interaction between gp120 and CCR-5 was dramatically lower in the absence of soluble CD4. Additionally, in the absence of gp120, an interaction between a two-domain CD4 fragment and CCR-5 was observed. A gp120 fragment retaining the CD4-binding site and overlapping epitopes was able to interact with CCR-5 only if the V3 loop, which can specify HIV-1 tropism and chemokine receptor choice, was also present on the molecule. Neutralizing antibodies directed against either CD4-induced or V3 epitopes on gp120 blocked the interaction of gp12O-CD4 complexes with CCR-5. These results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry.
Links	PubMed Online version:10.1038/384179a0
Keywords	Animals; Antibodies, Monoclonal/immunology; Antigens, CD4/metabolism; Binding Sites; Binding, Competitive; Chemokine CCL3; Chemokine CCL4; Drosophila; HIV Antibodies/immunology; HIV Envelope Protein gp120/immunology; HIV Envelope Protein gp120/metabolism; HIV-1/metabolism; Humans; Macrophage Inflammatory Proteins/metabolism; Membrane Fusion; Mice; Neutralization Tests; Peptide Fragments/metabolism; Receptors, CCR5; Receptors, Cytokine/metabolism; Receptors, HIV/metabolism; Recombinant Proteins/metabolism; Tumor Cells, Cultured
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HV1H2:ENV	involved_in	GO:0019062: virion attachment to host cell	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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