title: 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.
authors.affiliation: Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
authors.forename: Hung-Yao
authors.initials: HY
authors.lastname: Ho
authors.affiliation: Center for Gerontological Research, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.|Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
authors.forename: Shiue-Fen
authors.initials: SF
authors.lastname: Weng
authors.affiliation: Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
authors.forename: Lo
authors.initials: L
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
authors.forename: Tsun-Tsun
authors.initials: TT
authors.lastname: Yeh
authors.affiliation: Department of Clinical Pathology, Chang Gung Memorial Hospital, Kwei-san, Tao-yuan, Taiwan, ROC.|Graduate Institute of Basic Medical Sciences, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.|Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
authors.affiliation: Department of Clinical Pathology, Chang Gung Memorial Hospital, Kwei-san, Tao-yuan, Taiwan, ROC.|Graduate Institute of Basic Medical Sciences, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.|Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
authors.forename: Daniel Tsun-Yee
authors.initials: DT
authors.lastname: Chiu