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Cell Death Differ. 2002 Nov;9(11):1172-84.

HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear fragmentation.

Author information

1
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.

Abstract

Infection of T cells with HIV-1 induces apoptosis and modulates apoptosis regulatory molecules. Similar effects occur following treatment of cells with individual HIV-1 encoded proteins. While HIV-1 protease is known to be cytotoxic, little is known of its effect on apoptosis and apoptosis regulatory molecules. The ability of HIV-1 protease to kill cells, coupled with the degenerate substrate specificity of HIV-1 protease, suggests that HIV-1 protease may activate cellular factor(s) which, in turn, induce apoptosis. We demonstrate that HIV-1 protease directly cleaves and activates procaspase 8 in T cells which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, cleavage of DFF and PARP and, eventually, to nuclear condensation and DNA fragmentation that are characteristic of apoptosis. The effect of HIV-1 protease is not seen in T cell extracts which have undetectable levels of procaspase 8, indicating a specificity and requirement for procaspase 8.

PMID:
12404116
DOI:
10.1038/sj.cdd.4401094
[Indexed for MEDLINE]
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