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J Virol. 2009 Nov;83(21):11283-97. doi: 10.1128/JVI.00756-09. Epub 2009 Aug 19.

Virion-associated Vpr of human immunodeficiency virus type 1 triggers activation of apoptotic events and enhances fas-induced apoptosis in human T cells.

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Department of Microbiology, Immunology and Molecular Genetics, University of California at Los Angeles, David Geffen School of Medicine, 615 Charles E. Young Dr. South, BSRB 173, Los Angeles, CA 90095, USA.


Human immunodeficiency virus type 1 (HIV-1) Vpr protein exists in three different forms: soluble, intracellular, and virion associated. Previous studies showed that virion-associated Vpr induces apoptosis in activated peripheral blood mononuclear cells (PBMCs) and Jurkat T cells, but these studies were conducted in the presence of other de novo-expressed HIV proteins that may have had additive proapoptotic effects. In this report, we show that virion-associated Vpr triggers apoptosis through caspases 3/7 and 9 in human T cells independently of other HIV de novo-expressed proteins. In contrast to a previous study, we also detected the activation of caspase 8, the initiator caspase of the death receptor pathway. However, activation of all caspases by virion-associated Vpr was independent of the Fas death receptor pathway. Further analyses showed that virion-associated Vpr enhanced caspase activation in Fas-mediated apoptosis in Jurkat T cells and human activated PBMCs. Thus, our results indicate for the first time that viral particles that contain virion-associated Vpr can cause apoptosis in the absence of other de novo-expressed viral factors and can act in synergy with the Fas receptor pathway, thereby enhancing the apoptotic process in T cells. These findings suggest that virion-associated Vpr can contribute to the depletion of CD4(+) lymphocytes either directly or by enhancing Fas-mediated apoptosis during acute HIV-1 infection and in AIDS.

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