Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection.
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.
Ho
Hung-Yao
HY
Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
Cheng
Mei-Ling
ML
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.
Weng
Shiue-Fen
SF
Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
Chang
Lo
L
Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
Yeh
Tsun-Tsun
TT
Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kwei-san, Tao-yuan, Taiwan, ROC.
Shih
Shin-Ru
SR
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.
Chiu
Daniel Tsun-Yee
DT
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.