Human immunodeficiency virus type 1 Vpr induces apoptosis through caspase activation

被引:136
作者
Stewart, SA
Poon, B
Song, JY
Chen, ISY
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA
[3] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
关键词
D O I
10.1128/JVI.74.7.3105-3111.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 G(2)/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.
引用
收藏
页码:3105 / 3111
页数:7
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