CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5


THE β-chemokine receptor CCR-5 is an essential co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4+ T-cells1–5. The primary binding site for human immunodeficiency virus (HIV)-1 is the CD4 molecule, and the interaction is mediated by the viral surface glycoprotein gp120 (refs 6, 7). The mechanism of CCR-5 function during HIV-1 entry has not been defined, but we have shown previously that its β-chemokine ligands prevent HIV-1 from fusing with the cell1. We therefore investigated whether CCR-5 acts as a second binding site for HIV-1 simultaneously with or subsequent to the interaction between gp120 and CD4. We used a competition assay based on gp120 inhibition of the binding of the CCR-5 ligand, macrophage inflammatory protein (MIP)-1β, to its receptor on activated CD4+ T cells or CCR-5-positive CD4 cells. We conclude that CD4 binding, although not absolutely necessary for the gp120–CCR-5 interaction, greatly increases its efficiency. Neutralizing monoclonal antibodies against several sites on gp120, including the V3 loop and CD4-induced epitopes, inhibited the interaction of gp120 with CCR-5, without affecting gp120–CD4 binding. Interference with HIV-1 binding to one or both of its receptors (CD4 and CCR-5) may be an important mechanism of virus neutralization.

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Trkola, A., Dragic, T., Arthos, J. et al. CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature 384, 184–187 (1996).

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