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Journal of Undergraduate Research

Keywords

HIV-1, Prostratin treatment, highly active anti-retroviral therapy, HAART

College

Life Sciences

Department

Microbiology and Molecular Biology

Abstract

Due to recent findings that HIV replication can persist even with highly active anti-retroviral therapy (HAART), it has become increasingly necessary to develop new therapies that can be used as adjuncts with HAART, to combat HIV infection. One possible alternative strategy is to block infection by down-regulation of the cell receptors needed for viral entry. Amara, et al. proposed that HIV coreceptor down-regulation by stromal cell derived factor 1-a (SDF-1a), the physiological ligand of CXCR4, blocks infection of target cells by X4 strains of HIV-1 (1). Mack, et al. demonstrated that Aminooxypentane-RANTES (a derivative of RANTES, one of CCR5’s physiological ligands) induces CCR5 internalization and inhibits normal receptor recycling. They proposed that down-regulation of CCR5 by Aminooxypentane-RANTES may be an effective strategy for inhibiting entry of R5 strains of HIV-1 (2). Phorbol esters (activators of Protein Kinase C) such as Phorbol-12-Myristate-13-Acetate (PMA) and Phorbol Dibutyrate (PDBu) have been shown to down-regulate the surface expression of HIV-1 receptor CD4 and coreceptor CXCR4, and thus inhibit HIV-1 infection (3,4,5,6,7). These compounds have proved useful tools in elucidating the mechanisms of CXCR4 and CD4 regulation; however, due to their tumor-promoting activities, the use of phorbol esters to down-regulate HIV receptors and thus inhibit viral entry has been largely ignored. Because Prostratin is a non-tumor-promoting phorbol ester, we studied the anti-HIV effects of this compound (8,9,10,11).

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Microbiology Commons

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