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Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection.

Abstract
Variations in the cellular microenvironment affect the host's susceptibility to pathogens. Using glucose-6-phosphate dehydrogenase (G6PD)-deficient fibroblasts as a model, this study demonstrated that the cellular redox status affects infectivity as well as the outcome of enterovirus 71 (EV71) infection. Compared with their normal counterparts, G6PD-deficient cells supported EV71 replication more efficiently and showed greater cytopathic effect and loss of viability. Mechanistically, viral infection led to increased oxidative stress, as indicated by increased dichlorofluorescein fluorescence and a diminished ratio of glutathione (GSH) to its disulfide form (GSSG), with the effect being greater in G6PD-deficient cells. Exogenous expression of active G6PD in the deficient cells, which increased the intracellular GSH:GSSG ratio, suppressed the generation of viral progeny. Consistent with this, treatment with N-acetylcysteine offered resistance to EV71 propagation and a cytoprotective effect on the infected cells. These findings support the notion that G6PD status, and thus redox balance, is an important determinant of enteroviral infection.
AuthorsHung-Yao Ho, Mei-Ling Cheng, Shiue-Fen Weng, Lo Chang, Tsun-Tsun Yeh, Shin-Ru Shih, Daniel Tsun-Yee Chiu
JournalThe Journal of general virology (J Gen Virol) Vol. 89 Issue Pt 9 Pg. 2080-2089 (Sep 2008) ISSN: 0022-1317 [Print] England
PMID18753216 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • DNA, Viral
  • Glucosephosphate Dehydrogenase
  • Glutathione
  • Glutathione Disulfide
Topics
  • Antioxidants (pharmacology)
  • Base Sequence
  • Cells, Cultured
  • Cytopathogenic Effect, Viral
  • DNA, Viral (genetics)
  • Enterovirus A, Human (genetics, pathogenicity, physiology)
  • Enterovirus Infections (enzymology, etiology, prevention & control, virology)
  • Glucosephosphate Dehydrogenase (metabolism)
  • Glucosephosphate Dehydrogenase Deficiency (complications, metabolism, virology)
  • Glutathione
  • Glutathione Disulfide (metabolism)
  • Humans
  • Oxidative Stress
  • Viral Plaque Assay
  • Virulence
  • Virus Replication

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