CD4-INDEPENDENT INFECTION BY HIV-2 IS MEDIATED BY FUSIN CXCR4/

Several members of the chemokine receptor family have been shown to fu nction in association with CD4 to permit HIV-1 entry and infection. Ho wever, the mechanism by which these molecules serve as CD4-associated cofactors is unclear. In the present report, we show that one member o f this family, termed Fusin/ CXCRL1, is able to function as an alterna tive receptor for some isolates of HIV-2 in the absence of CD4. This c onclusion is supported by the finding that (1) CD4-independent infecti on by these viruses is inhibited by an anti-fusin monoclonal antibody, (2) Fusin expression renders human and nonhuman CD4-negative cell lin es sensitive to HIV-P-induced syncytium induction and/or infection, an d (3) Fusin is selectively downregulated from the cell surface followi ng HIV-2 infection. The finding that one chemokine receptor can functi on as a primary viral receptor strongly suggests that the HIV envelope glycoprotein contains a binding site for these proteins and that diff erences in the affinity and/or the availability of this site can exten d the host range of these viruses to include a number of CD4-negative cell types.