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RANTES-Induced Enhancement of Virus Infectivity: Cell Compartments Involved in Mediating the RANTES Signal and Their Link to the Virus Life Cycle C. GORDON*1,2, T. CHANG1, A. E. I. PROUDFOOT3, J. P. MOORE1, and A. TRKOLA1. 1Aaron Diamond AIDS Res. Ctr., The Rockefeller Univ., New York, NY; 2New York Univ., NY; and 3Serono Pharm. Res. Inst., Geneva, Switzerland We have previously shown that prolonged treatment with RANTES causes an alteration in the physiology of target cells that increases their susceptibility to infection with HIV-1 and other viruses. The activation pathway is mediated by tyrosine kinase-dependent signals that are triggered when RANTES interacts with cell surface glycosaminoglycan (GAG) receptors. Here we study the effect of RANTES on various cell compartments (including membrane proteins, src kinase signaling cascade components, and cytoskeleton proteins) that have been implicated in the HIV-1 life cycle. We demonstrate that the surface expression of the proteoglycan CD44 is upregulated while the proteoglycan syndecan-1 is moderately downregulated. The surface expression of the CD40 molecule on HeLA cells is also dramatically downregulated by RANTES. The effect of RANTES on viral infectivity in the absence or presence of these various receptors will be shown. We have also found that kinases of the src family are involved in the RANTES-induced enhancement of HIV-1 infectivity, and that an intact actin cytoskeleton is obligatory for this effect to occur. How the known associations between syndecan-1, src kinases and actin filaments influence HIV-1 infectivity will be a focus of this presentation. Key Words: Glycosaminoglicans, HIV-1, RANTES |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |