Membrane raft microdomains mediate lateral assemblies required for HIV-1 infection

HIV-1 infection triggers lateral membrane diffusion following interaction o f the viral envelope with cell surface receptors. We show that these membra ne changes are necessary for infection, as initial gp120-CD4 engagement lea ds to redistribution and clustering of membrane microdomains, enabling subs equent interaction of this complex with HIV-1 co-receptors. Disruption of c ell membrane rafts by cholesterol depletion before viral exposure inhibits entry by both X4 and R5 strains of HIV-1, although viral replication in inf ected cells is unaffected by this treatment. This inhibitory effect is full y reversed by cholesterol replenishment of the cell membrane. These results indicate a general mechanism for HIV-1 envelope glycoprotein-mediated fusi on by reorganization of membrane microdomains in the target cell, and offer new strategies for preventing HIV-1 infection.