Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis through Caspase Activation

doi:10.1128/JVI.74.7.3105-3111.2000

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Journal of Virology, April 2000, p. 3105-3111, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis through Caspase Activation

Sheila A. Stewart, Betty Poon, Joo Y. Song, and Irvin S. Y. Chen^*

Departments of Microbiology and Immunology and Medicine, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095

Received 7 May 1999/Accepted 7 January 2000

Human immunodeficiency virus type 1 (HIV-1) Vpr is a 96-amino-acid protein that is found associated with the HIV-1 virion.Vpr induces cell cycle arrest at the G₂/M phase of the cell cycle,and this arrest is followed by apoptosis. We examined the mechanismof Vpr-induced apoptosis and found that HIV-1 Vpr-induced apoptosisrequires the activation of a number of cellular cysteinyl aspartate-specificproteases (caspases). We demonstrate that ectopic expression ofanti-apoptotic viral proteins, which inhibit caspase activity,and addition of synthetic peptides, which represent caspase cleavagesites, can inhibit Vpr-induced apoptosis. Finally, inhibitionof caspase activity and subsequent inhibition of apoptosis resultsin increased viral expression, suggesting that therapeutic strategiesaimed at reducing Vpr-induced apoptosis in vivo require carefulconsideration.

^* Corresponding author. Mailing address: Departments of Microbiology & Immunology and Medicine, UCLA School of Medicine andJonsson Comprehensive Cancer Center, 11-934 Louis Factor Bldg.,10833 Le Conte Ave., Los Angeles, CA 90095-1678. Phone: (310)825-4793. Fax: (310) 794-7682. E-mail: rtaweesu{at}ucla.edu.

Present address: Whitehead Institute for Biomedical Research, Cambridge, MA02142.

Journal of Virology, April 2000, p. 3105-3111, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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