SIGNAL-TRANSDUCTION DUE TO HIV-1 ENVELOPE INTERACTIONS WITH CHEMOKINERECEPTORS CXCR4 OR CCR5

Infection with HIV-1 requires expression of CD4 and the chemokine rece ptors CXCR4 or CCR5 at the target cell surface. Engagement of these re ceptors by the HIV-1 envelope glycoprotein is essential for membrane f usion, but may additionally activate intracellular signaling pathways. In this study, we demonstrate that chemokines and HIV-1 envelope glyc oproteins from both T-tropic and macrophage-tropic strains rapidly ind uce tyrosine phosphorylation of the protein tyrosine kinase Pyk2. The response requires CXCR3 and CCR5 to be accessible on the cell surface. The results presented here provide the first evidence for activation of an intracellular signaling event that can initiate multiple signali ng pathways as a consequence of contact between HIV-1 and chemokine re ceptors.