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Role of Oxidative Stress in West Nile Virus (WNV)‐ induced Apoptosis
Author(s) -
Verma Saguna,
Molina Y.,
Lo Y. Y.,
Cropp C. B.,
Arai S.,
Nakano C. M.,
Yanagihara R.,
Nerurkar V. R.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1073-b
Subject(s) - oxidative stress , reactive oxygen species , superoxide dismutase , biology , apoptosis , programmed cell death , microbiology and biotechnology , biochemistry
WNV, a mosquito‐borne flavivirus, causes lethal encephalitis in humans and horses. In humans, apoptotic cell death has been implicated as a cytopathogenic mechanism in response to WNV infection. However, the underlying host‐specific factors and the mechanisms for WNV pathogenicity are poorly understood. Oxidative stress, primarily due to increased generation of reactive oxygen species (ROS) and decreased antioxidant capacity, leads to host‐cell apoptosis in several viral infections. We hypothesized that increased ROS production plays a critical role in the pathogenesis of WNV‐induced neuroinflammation. Our objective was to delineate the molecular mechanisms underlying host oxidative stress response, following infection with WNV NY99 and Eg101 strains in Vero and human neuroblastoma cells, by measuring the production of superoxide anion radical (O2.−) and levels of key antioxidant enzymes, like superoxide dismutases (CuZnSOD and MnSOD), glutathione peroxidase (GPx1), catalase and inducible nitric oxide synthase. Further, the direct role of WNV‐induced ROS in activating the NF‐kB signaling pathway and initiating apoptosis was investigated using markers such as degradation of intracellular i‐kB and cytochrome c release by mitochondria, in the presence and absence of ROS inhibitors. Our results demonstrate that both WNV strains induce a dose‐dependent increase of O2.–in both cell types, with concomitant increase in MnSOD and Gpx1 mRNA and protein expression. Furthermore, ROS inhibitors partially reversed the levels of apoptosis markers. Thus, our findings indicate that cellular components of the oxidant/antioxidant system do respond to WNV infection, and may trigger apoptotic cell death via activation of the NF‐kB signaling pathway.