MACROPHAGE-TROPIC HIV AND SIV ENVELOPE PROTEINS INDUCE A SIGNAL THROUGH THE CCR5 CHEMOKINE RECEPTOR

Human immunodeficiency virus (HIV) and simian immunodeficiency virus ( SIV) enter target cells by forming a complex between the viral envelop e protein and two cell-surface membrane receptors: CD4 and a 7-span tr ansmembrane chemokine receptor (reviewed in refs 1-3). Isolates of HIV that differ in cellular tropism use different subsets of chemokine re ceptors as entry cofactors: macrophage-tropic HIVs primarily use CCR5, whereas T-cell-tropic and dual-tropic isolates use CXCR4 (refs 1-3) r eceptors. HIV-mediated signal transduction through CCR5 is not require d for efficient fusion and entry of HIV in vitro(4,5). Here we show th at recombinant envelope proteins from macrophage-tropic HIV and SIV in duce a signal through CCR5 on CD4(+) T cells and that envelope-mediate d signal transduction through CCR5 induces chemotaxis of T cells. This chemotactic response may contribute to the pathogenesis of HIV in viv o by chemo-attracting activated CD4(+) cells to sites of viral replica tion(1,2). HIV-mediated signalling through CCR5 may also enhance viral replication in vivo by increasing the activation state of target cell s. Alternatively, envelope-mediated CCR5 signal transduction may influ ence viral-associated cytopathicity or apoptosis.