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Functional studies of an HIV‐1 encoded glutathione peroxidase
Author(s) -
Zhao Lijun,
Olubajo Babatunde,
Taylor Ethan Will
Publication year - 2006
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520270109
Subject(s) - peroxynitrite , reactive oxygen species , arginine , biology , oxidative stress , glutathione peroxidase , biochemistry , microbiology and biotechnology , chemistry , superoxide , superoxide dismutase , enzyme , amino acid
In an alternate reading frame overlapping the viral envelope gene, HIV‐1 has been shown to encoded a truncated glutathione peroxidase (GPx) module. Essential active site residues of the catalytic core regions of mammalian GPx sequences are conserved in the putative viral GPx (vGPx, encoded by the env‐fs gene). Cells transfected with an HIV‐1 env‐fs construct show up to a 100% increase in GPx enzyme activity, and are protected against the loss of mitochondrial transmembrane potential and subsequent cell death induced by exogenous oxidants or mitochondrial reactive oxygen species. An intact vGPx gene was observed to be more common in HIV‐1‐infected long‐term non‐progressors, as compared to HIV‐1 isolates from patients developing AIDS. An antioxidant/antiapoptotic protective role of the vGPx is also consistent with the observation that −1 frameshifting induced by the HIV‐1 env‐fs sequence GA (which contains a potential “hungry” arginine codon, AGA) increases during arginine deficiency, which has been associated with increased oxidative stress. Under arginine‐limited conditions, nitric oxide synthase generates superoxide, which rapidly combines with NO to form peroxynitrite, which can cause activated T‐cells to undergo apoptosis. Thus, biosynthesis of the HIV‐1 GPx as an adaptive response to low arginine conditions might delay oxidant‐induced apoptotic cell death, providing an enhanced opportunity for viral replication.