BETA-CHEMOKINE INHIBITION OF MONOCYTOTROPIC HIV-1 INFECTION - INTERFERENCE WITH A POSTBINDING FUSION STEP

The beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta have potent su ppressive effects on HIV-1 infection resulting from an early postbindi ng block in virus fusion and entry, inhibition was observed only with monocytotropic isolates and mapped to the V3 region of the HIV-1 envel ope. RANTES did not inhibit virus expression in chronically infected c ells or reduce initial virus attachment to the cell membrane. Inhibito ry activity required RANTES binding to the target cell but not G prote in-mediated signaling or protein tyrosine kinase activity. The results are consistent with a reversible competitive mechanism of virus inhib ition that prevents a V3-associated postbinding step in membrane fusio n. The data support a role for a RANTES chemokine receptor as a corece ptor for monocytotropic HIV-1.