T cell-tropic HIV gp120 mediates CD4 and CD8 cell chemotaxis through CXCR4independent of CD4: Implications for HIV pathogenesis

HIV entry is determined by one or more chemokine receptors, T cell-tropic v iruses bind CXCR4, whereas macrophage-tropic viruses use CCR5 and other CCR s, Infection with CXCR4 and CCR5-tropic HIV requires initial binding to CD4 , and chemotaxis induced by the CCR5-tropic envelope has been reported to b e strictly dependent on CD4 binding. We demonstrate that, in contrast to CD 4-dependent gp120 signaling via CCR5, envelope signaling through CXCR4 is C D4 independent, inducing chemotaxis of both CD4 and CDS T cells, Signaling by virus or soluble envelope through CXCR4 may affect pathogenesis by attra cting and activating target and effector cells.