Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection
Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection
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DOI：
10.1099/vir.0.2008/001404-0
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发表时间：
2008-09-01
影响因子：
3.8
通讯作者：
Chiu, Daniel Tsun-Yee
中科院分区：
文献类型：
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作者：
Ho, Hung-Yao;Cheng, Mei-Ling;Chiu, Daniel Tsun-Yee
细胞微环境的变化影响宿主对病原体的易感性。本研究以葡萄糖-6-磷酸脱氢酶（G6 PD）缺陷型成纤维细胞为模型，证明细胞氧化还原状态影响肠道病毒71（EV 71）感染的传染性和结果。与正常细胞相比，G6 PD缺陷细胞更有效地支持EV 71的复制，并表现出更大的细胞病变效应和活力丧失。从机制上讲，病毒感染导致氧化应激增加，如二氯荧光素荧光增加和谷胱甘肽（GSH）与其二硫键形式（GSSG）的比例降低所示，在G6 PD缺陷细胞中效果更大。在缺陷细胞中外源表达活性G6 PD，这增加了细胞内GSH：GSSG比率，抑制了病毒后代的产生。与此一致，用N-乙酰半胱氨酸处理提供了对EV 71繁殖的抗性和对感染细胞的细胞保护作用。这些发现支持了G6 PD状态以及氧化还原平衡是肠道病毒感染的重要决定因素的观点。
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.