Infected Cell Killing by HIV-1 Protease Promotes NF-κB Dependent HIV-1 Replication

被引:23
作者
Bren, Gary D. [1 ]
Whitman, Joe [1 ]
Cummins, Nathan [1 ]
Shepard, Brett [1 ]
Rizza, Stacey A. [1 ,2 ]
Trushin, Sergey A. [1 ]
Badley, Andrew D. [1 ,2 ]
机构
[1] Mayo Clin, Div Infect Dis, Rochester, MN 55905 USA
[2] Mayo Clin, Program Translat Immunovirol & Biodefense, Rochester, MN USA
来源
PLOS ONE | 2008年 / 3卷 / 05期
基金
美国国家卫生研究院;
关键词
D O I
10.1371/journal.pone.0002112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Acute HIV-1 infection of CD4 T cells often results in apoptotic death of infected cells, yet it is unclear what evolutionary advantage this offers to HIV-1. Given the independent observations that acute T cell HIV-1 infection results in (1) NF-kappa B activation, (2) caspase 8 dependent apoptosis, and that (3) caspase 8 directly activates NF-kappa B, we questioned whether these three events might be interrelated. We first show that HIV-1 infected T cell apoptosis, NF-kappa B activation, and caspase 8 cleavage by HIV-1 protease are coincident. Next we show that HIV-1 protease not only cleaves procaspase 8, producing Casp8p41, but also independently stimulates NF-kappa B activity. Finally, we demonstrate that the HIV protease cleavage of caspase 8 is necessary for optimal NF-kappa B activation and that the HIV-1 protease specific cleavage fragment Casp8p41 is sufficient to stimulate HIV-1 replication through NF-kappa B dependent HIV-LTR activation both in vitro as well as in cells from HIV infected donors. Consequently, the molecular events which promote death of HIV-1 infected T cells function dually to promote HIV-1 replication, thereby favoring the propagation and survival of HIV-1.
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页数:7
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