The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway.
Cell Death Differ
; 9(11): 1212-9, 2002 Nov.
Article
em En
| MEDLINE
| ID: mdl-12404120
ABSTRACT
Previous biochemical studies suggested that HIV-1-encoded Vpr may kill cells through an effect on the adenine nucleotide translocase (ANT), thereby causing mitochondrial membrane permeabilization (MMP). Here, we show that Vpr fails to activate caspases in conditions in which it induces cell killing. The knock-out of essential caspase-activators (Apaf-1 or caspase-9) or the knock-out of a mitochondrial caspase-independent death effector (AIF) does not abolish Vpr-mediated killing. In contrast, the cytotoxic effects of Vpr are reduced by transfection-enforced overexpression of two MMP-inhibitors, namely the endogenous protein Bcl-2 or the cytomegalovirus-encoded ANT-targeted protein vMIA. Vpr, which can elicit MMP through a direct effect on mitochondria, and HIV-1-Env, which causes MMP through an indirect pathway, exhibit additive (but not synergic) cytotoxic effects. In conclusion, it appears that Vpr induces apoptosis through a caspase-independent mitochondrial pathway.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
/
HIV-1
/
Apoptose
/
Produtos do Gene vpr
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
Cell Death Differ
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
França