Mechanism of HIV-1 viral protein R-induced apoptosis |
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Authors: | Muthumani Karuppiah Choo Andrew Y Hwang Daniel S Chattergoon Michael A Dayes Nathanael N Zhang Donghui Lee Mark D Duvvuri Umaheswar Weiner David B |
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Institution: | Department of Pathology and Laboratory Medicine, University of Pennsylvania, 505 Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA. |
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Abstract: | The paradigm of HIV-1 infection includes the diminution of CD4(+) T cells, loss of immune function, and eventual progression to AIDS. However, the mechanisms that drive host T cell depletion remain elusive. One HIV protein thought to participate in this destructive cascade is the Vpr gene product. Accordingly, we review the biology of the HIV-1 viral protein R (Vpr) an apoptogenic HIV-1 accessory protein that is packaged into the virus particle. In this review we focus specifically on Vpr's ability to induce host cell apoptosis. Recent evidence suggests that Vpr implements a unique mechanism to drive host cell apoptosis, by directly depolarizing the mitochondria membrane potential. Vpr's attack on the mitochondria results in release of cytochrome c resulting in activation of the caspase 9 pathway culminating in the activation of caspase 3 and the downstream events of apoptosis. Vpr may interact with the adenine nucleotide translocator (ANT) to prompt this cascade. The role of Vpr-induced apoptosis in HIV pathogenesis is considered. |
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Keywords: | HIV-1 Vpr Apoptosis Caspase Mitochondrial membrane potential NF-κB AIF Cytochrome c |
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