The Influenza Virus H5N1 Infection Can Induce ROS Production for Viral Replication and Host Cell Death in A549 Cells Modulated by Human Cu/Zn Superoxide Dismutase (SOD1) Overexpression.
The Influenza Virus H5N1 Infection Can Induce ROS Production for Viral Replication and Host Cell Death in A549 Cells Modulated by Human Cu/Zn Superoxide Dismutase (SOD1) Overexpression.
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DOI：
10.3390/v8010013
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发表时间：
2016-01-08
期刊：
影响因子：
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通讯作者：
Jin M
中科院分区：
文献类型：
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作者：
Lin X;Wang R;Zou W;Sun X;Liu X;Zhao L;Wang S;Jin M
高致病性H5N1感染往往伴随着过度的促炎反应、高病毒滴度和细胞凋亡；因此，有效控制这些感染是一个巨大的挑战。流感病毒感染的发病机制也与氧化应激有关。然而，具有抗氧化作用的内源性基因在控制流感病毒，特别是H5N1病毒中的作用有待进一步研究。在本研究中，H5N1病毒感染肺上皮细胞后，铜/锌超氧化物歧化酶(SOD1)在mRNA和蛋白水平的表达均下降。强制表达SOD1显著抑制了H5N1诱导的活性氧增加，降低了促炎反应，阻止了p65和p38的磷酸化，并阻止了病毒核蛋白的核输出和病毒复制。SOD1的过表达还挽救了H5N1诱导的细胞凋亡，缓解了H5N1诱导的线粒体功能障碍。因此，本研究描述了SOD1在H5N1流感病毒复制中的作用，并强调了该酶在控制H5N1上皮细胞复制中的相关性。药物调节或靶向SOD1可能为抗击H5N1流感病毒开辟新的途径。
Highly pathogenic H5N1 infections are often accompanied by excessive pro-inflammatory response, high viral titer, and apoptosis; as such, the efficient control of these infections poses a great challenge. The pathogenesis of influenza virus infection is also related to oxidative stress. However, the role of endogenic genes with antioxidant effect in the control of influenza viruses, especially H5N1 viruses, should be further investigated. In this study, the H5N1 infection in lung epithelial cells decreased Cu/Zn superoxide dismutase (SOD1) expression at mRNA and protein levels. Forced SOD1 expression significantly inhibited the H5N1-induced increase in reactive oxygen species, decreased pro-inflammatory response, prevented p65 and p38 phosphorylation, and impeded viral ribonucleoprotein nuclear export and viral replication. The SOD1 overexpression also rescued H5N1-induced cellular apoptosis and alleviated H5N1-caused mitochondrial dysfunction. Therefore, this study described the role of SOD1 in the replication of H5N1 influenza virus and emphasized the relevance of this enzyme in the control of H5N1 replication in epithelial cells. Pharmacological modulation or targeting SOD1 may open a new way to fight H5N1 influenza virus.