Affiliations: Office of Research and Department of Chemistry and
Biochemistry, University of North Carolina at Greensboro, PO Box 26170,
Greensboro, NC 27402-6170, USA | Department of Pharmaceutical and Biomedical Sciences,
College of Pharmacy, University of Georgia, Athens GA, 30602 USA
Abstract: 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
AAAAAGA (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.
