Enterovirus 71 induces mitochondrial reactive oxygen species generation that is required for efficient replication.
Enterovirus 71 induces mitochondrial reactive oxygen species generation that is required for efficient replication.
复制标题
DOI：
10.1371/journal.pone.0113234
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ho HY
中科院分区：
文献类型：
--
作者：
Cheng ML;Weng SF;Kuo CH;Ho HY
氧化还原稳态是决定传染病结果的重要宿主因素。肠道病毒71型（EV71）感染已成为东南亚和中国的重要地方病。我们之前已经证明，氧化应激会促进病毒复制，而子代病毒会在宿主细胞中诱导氧化应激。受感染细胞中活性氧（ROS）产生的详细机制仍然难以捉摸。在当前的研究中，我们证明线粒体是 EV71 感染细胞中主要的 ROS 来源。有效感染细胞中的线粒体经历了形态变化并表现出功能异常，例如线粒体电化学电位 ΔΨm 降低和寡霉素不敏感的耗氧量增加。感染细胞线粒体的呼吸控制率显着低于正常细胞。 EV71感染细胞的总腺嘌呤核苷酸池和ATP含量显着减少。然而，线粒体质量似乎出现了代偿性增加。 mito-TEMPO 治疗降低了 eIF2α 磷酸化和病毒复制，表明线粒体 ROS 具有促进病毒复制的作用。 EV71感染可能会诱导线粒体ROS的产生，这对于病毒复制至关重要，但会牺牲有效的能量产生，并且受感染的细胞会上调线粒体的生物发生以补偿其功能缺陷。
Redox homeostasis is an important host factor determining the outcome of infectious disease. Enterovirus 71 (EV71) infection has become an important endemic disease in Southeast Asia and China. We have previously shown that oxidative stress promotes viral replication, and progeny virus induces oxidative stress in host cells. The detailed mechanism for reactive oxygen species (ROS) generation in infected cells remains elusive. In the current study, we demonstrate that mitochondria were a major ROS source in EV71-infected cells. Mitochondria in productively infected cells underwent morphologic changes and exhibited functional anomalies, such as a decrease in mitochondrial electrochemical potential ΔΨm and an increase in oligomycin-insensitive oxygen consumption. Respiratory control ratio of mitochondria from infected cells was significantly lower than that of normal cells. The total adenine nucleotide pool and ATP content of EV71-infected cells significantly diminished. However, there appeared to be a compensatory increase in mitochondrial mass. Treatment with mito-TEMPO reduced eIF2α phosphorylation and viral replication, suggesting that mitochondrial ROS act to promote viral replication. It is plausible that EV71 infection induces mitochondrial ROS generation, which is essential to viral replication, at the sacrifice of efficient energy production, and that infected cells up-regulate biogenesis of mitochondria to compensate for their functional defect.
登录
查看更多内容
影响因子：
64.5
作者：
Giorgio, M;Migliaccio, E;Pelicci, PG
通讯作者：
Pelicci, PG
影响因子：
5.4
作者：
Claus, C.;Schoenefeld, K.;Liebert, U. G.
通讯作者：
Liebert, U. G.
影响因子：
5.2
作者：
Ho, Hung-Yao;Cheng, Mei-Ling;Chiu, Daniel Tsun-Yee
通讯作者：
Chiu, Daniel Tsun-Yee
影响因子：
2.2
作者：
Anand SK;Tikoo SK
通讯作者：
Tikoo SK
影响因子：
3.8
作者：
Ho, Hung-Yao;Cheng, Mei-Ling;Chiu, Daniel Tsun-Yee
通讯作者：
Chiu, Daniel Tsun-Yee