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Journal of Virology, November 2009, p. 11283-11297, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.00756-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Virion-Associated Vpr of Human Immunodeficiency Virus Type 1 Triggers Activation of Apoptotic Events and Enhances Fas-Induced Apoptosis in Human T Cells{triangledown}

Hubert Arokium, Masakazu Kamata, and Irvin Chen*

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

Received 13 April 2009/ Accepted 11 August 2009

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.

* Corresponding author. Mailing address: 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. Phone: (310) 825-4793. Fax: (310) 267-1875. E-mail: syuchen{at}mednet.ucla.edu

{triangledown} Published ahead of print on 19 August 2009.

Journal of Virology, November 2009, p. 11283-11297, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.00756-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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