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Pathogenesis and Immunity

Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis through Caspase Activation

Sheila A. Stewart, Betty Poon, Joo Y. Song, Irvin S. Y. Chen
Sheila A. Stewart
Departments of Microbiology and Immunology and Medicine, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095
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Betty Poon
Departments of Microbiology and Immunology and Medicine, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095
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Joo Y. Song
Departments of Microbiology and Immunology and Medicine, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095
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Irvin S. Y. Chen
Departments of Microbiology and Immunology and Medicine, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095
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DOI: 10.1128/JVI.74.7.3105-3111.2000
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ABSTRACT

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 mechanism of Vpr-induced apoptosis and found that HIV-1 Vpr-induced apoptosis requires the activation of a number of cellular cysteinyl aspartate-specific proteases (caspases). We demonstrate that ectopic expression of anti-apoptotic viral proteins, which inhibit caspase activity, and addition of synthetic peptides, which represent caspase cleavage sites, can inhibit Vpr-induced apoptosis. Finally, inhibition of caspase activity and subsequent inhibition of apoptosis results in increased viral expression, suggesting that therapeutic strategies aimed at reducing Vpr-induced apoptosis in vivo require careful consideration.

  • Copyright © 2000 American Society for Microbiology
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Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis through Caspase Activation
Sheila A. Stewart, Betty Poon, Joo Y. Song, Irvin S. Y. Chen
Journal of Virology Apr 2000, 74 (7) 3105-3111; DOI: 10.1128/JVI.74.7.3105-3111.2000

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Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis through Caspase Activation
Sheila A. Stewart, Betty Poon, Joo Y. Song, Irvin S. Y. Chen
Journal of Virology Apr 2000, 74 (7) 3105-3111; DOI: 10.1128/JVI.74.7.3105-3111.2000
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KEYWORDS

apoptosis
caspases
Gene Products, vpr
HIV-1

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