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Functional Responses of Human Primary Cells to HIV-1 Envelope Glycoprotein, gp120 C. M. MCMANUS, F. BARIBAUD, Y. GIRARD, B. LEE, and R. W. DOMS. Univ. of Pennsylvania, Philadelphia The HIV envelope glycoprotein, gp120, (Env) plays an important role in HIV entry. Entry of HIV into host cells requires the interaction of Env with two receptors on the surface of the cell, CD4 and a co-receptor. The co-receptors are members of the seven transmembrane spanning-G-protein coupled chemokine receptor family. The major co-receptors for HIV entry are CCR5 and CXCR4 and the viruses which utilize these receptors are classified as R5 and X4 respectively. In order for the Env to bind to the chemokine receptor it first interacts with CD4 which causes conformational changes in Env which allow subsequent interactions with the co-receptor. It has been proposed that Env may have other functions involved in post-entry events and other cellular modifications by inducing signals via coreceptor interactions. We are interested in determining the role of various X4 and R5 Envs in eliciting functional responses from human primary peripheral blood cells. We have analyzed the ability of JR-FL, an R5 gp120 and IIIB, an X4 gp120, to upregulate activation markers on PBMCs potentially eliciting chemotaxis or apoptosis of these cells. JR-FL upregulated CD18 and CD69 on PBMCs and this upregulation was blocked by an antibody to CCR5. We also showed JR-FL to have a strong, specific chemotactic effect on PBMCs. Additional interests lie in the downstream signaling events which may be mediated as a result of Env-receptor interaction. We have preliminary data showing the internalization of the receptors following Env interaction is a clathrin-mediated event and there are resulting phosphorylation events which also occur. These events may result in the expression of factors involved in cell adhesion, motility, or cell death. The ability of Env to elicit cellular responses in the absence of infection may have important implications for cellular trafficking and spread of virus in vivo. Key Words: chemokine receptors, chemotaxis, gp120 |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |