Anti-apoptotic activity of the glutathione peroxidase homologue encoded by HIV-1.
The third reading frame of the envelope gene from HIV-1 codes for a protein homologous to the human selenoprotein glutathione peroxidase (GPX). Cells stably or transiently transfected with a HIV-1 GPX construct are protected against the loss of the mitochondrial transmembrane potential and subsequent cell death induced by exogenous reactive oxygen species (ROS) as well as mitochondrion-generated ROS. However, HIV-1 GPX does not confer a general apoptosis resistance, because HIV-1 GPX-transfected cells were not protected against cell death induced by staurosporine or oligomycin. The inhibition of cell death induced by the ROS donor tert-butylhydroperoxide was also observed in cells depleted from endogenous glutathione (GSH), suggesting that GSH is not the sole electron acceptor for HIV-1 GPX. Clinical HIV-1 isolates from long-term non-progressors (untreated patients with diagnosed HIV-1 infection for > 10 years, with CD4 T cell count of > 500 cells/mm3) mostly possess an intact GPX gene (with only 18% of loss-of-function mutations), while HIV-1 isolates from patients developing AIDS contain non-functional GPX mutants in 9 out of 17 cases (53%). Altogether, these data suggest that HIV-1 GPX possesses a cytoprotective, pathophysiologically relevant function.
Cohen
I
I
CNRS-UMR8125, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France.
Boya
P
P
Zhao
L
L
Métivier
D
D
Andreau
K
K
Perfettini
J-L
JL
Weaver
J G
JG
Badley
A
A
Taylor
E W
EW
Kroemer
G
G
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D017124:Conserved Sequence; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D005978:Glutathione