In vitro effects of selenium deficiency on West Nile virus replication and cytopathogenicity.
BACKGROUND
Selenium (Se) deficiency plays an important role in viral pathogenesis. To understand the effects of Se deficiency on West Nile virus (WNV) infection, we analyzed cytopathogenicity, apoptosis and viral replication kinetics, using a newly developed Se-deficient cell culture system.


RESULTS
Both Vero and SK-N-SH cells grown in Se-deficient media exhibited a gradual loss of glutathione peroxidase (GPx1) activity without any significant effect on cell growth and viability. In SK-N-SH cells, Se deficiency had no effect on the expression of key antioxidant enzymes, including manganese- and copper-zinc superoxide dismutase (MnSOD and CuZnSOD), catalase and inducible nitric oxide synthase, whereas Vero cells demonstrated a significant increase in the expression of MnSOD and an overall increase in oxidative stress (OS) at day 7 post-induction of Se deficiency. At 2 days after infection with WNV, CPE and cell death were significantly higher in WNV-infected Se-deficient Vero cells, compared to WNV-infected control cells. Furthermore, WNV-induced apoptosis was significantly heightened in Se-deficient cells and was contributed by loss of mitochondrial membrane potential and increased caspase activity. However, no significant difference was found in WNV copy numbers between control, Se-adequate and Se-deficient cell cultures.


CONCLUSIONS
Overall results demonstrate that the in vitro Se-deficient model can be used to study responses of WNV to this essential nutrient. Although Se deficiency has no in vitro effect on WNV replication kinetics, adequate Se is presumably critical to protect WNV-infected cells against virus-induced cell death.
Retrovirology Research Laboratory, Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A, Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA. saguna@hawaii.edu
Saguna
S
Verma
Yanira
Y
Molina
Yeung Y
YY
Lo
Bruce
B
Cropp
Cheynie
C
Nakano
Richard
R
Yanagihara
Vivek R
VR
Nerurkar
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor / Q000502:physiology / Q000821:virology; D002522:Chlorocebus aethiops; D003470:Culture Media; D003588:Cytopathogenic Effect, Viral; D006801:Humans; D018384:Oxidative Stress; D012643:Selenium; D014709:Vero Cells / Q000502:physiology / Q000821:virology; D014779:Virus Replication; D014901:West Nile Fever / Q000821:virology*; D014902:West Nile virus / Q000502:physiology*
D003470:Culture Media; D012643:Selenium