HIV-1 Vpr Induces Apoptosis through Caspase 9 in T Cells and Peripheral Blood Mononuclear Cells

Human immunodeficiency virus, type 1 (HIV-1),vpr gene encodes a 14-kDa virion-associated protein, which exhibits significant effects on human cells. One important property of Vpr is its ability to induce apoptosis during infection. Apoptotic induction is likely to play a role in the pathogenesis of...

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Published in:The Journal of biological chemistry 2002-10, Vol.277 (40), p.37820-37831
Main Authors: Muthumani, Karuppiah, Hwang, Daniel S., Desai, Brijal M., Zhang, Donghui, Dayes, Nathanael, Green, Douglas R., Weiner, David B.
Format: Article
Language:English
Subjects:
Annexin A5 - pharmacology
Apoptosis - drug effects
Apoptosis - physiology
Caspase 9
Caspases - metabolism
Cell Cycle - physiology
Cell Line
Gene Products, vpr - physiology
HeLa Cells
HIV-1 - genetics
Humans
Jurkat Cells
Neutrophils - physiology
Neutrophils - virology
T-Lymphocytes - physiology
T-Lymphocytes - virology
Virion - physiology
vpr Gene Products, Human Immunodeficiency Virus
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Summary:Human immunodeficiency virus, type 1 (HIV-1),vpr gene encodes a 14-kDa virion-associated protein, which exhibits significant effects on human cells. One important property of Vpr is its ability to induce apoptosis during infection. Apoptotic induction is likely to play a role in the pathogenesis of AIDS. However, the pathway of apoptosis is not clearly defined. In this report we investigate the mechanism of apoptosis induced by HIV-1 Vpr using a Vpr pseudotype viral infection system or adeno delivery of Vpr in primary human lymphoid cells and T-cells. With either vector, HIV-1 Vpr induced cell cycle arrest at the G2/M phase and apoptosis in lymphoid target cells. Furthermore, we observed that with both vectors, caspase 9, but not caspase 8, was activated following infection of human peripheral blood mononuclear cell with either Vpr-positive HIV virions or adeno-delivered Vpr. Activation of the caspase 9 pathway resulted in caspase 3 activation and apoptosis in human primary cells. These effects were coincident with the disruption of the mitochondrial transmembrane potential and induction of cytochrome c release by Vpr. The Vpr-induced signaling pathway did not induce CD95 or CD95L expression. Bcl-2 overexpressing cells succumb to Vpr-induced apoptosis. These studies illustrate that Vpr induces a mitochondria-dependent apoptotic pathway that is distinct from apoptosis driven by the Fas-FasL pathway.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M205313200