Reactive oxygen species (ROS) are chemically active species which are involved in maintaining cellular and signalling processes at physiological concentrations. Therefore, cellular components that regulate redox balance are likely to play a crucial role in viral life-cycle either as promoters of viral replication or with antiviral functions. Zinc is an essential micronutrient associated with anti-oxidative systems and helps in maintaining a balanced cellular redox state. Here, we show that zinc chelation leads to induction of reactive oxygen species (ROS) in epithelial cells and addition of zinc restores ROS levels to basal state. Addition of ROS (H2O2) inhibited dengue virus (DENV) infection in a dose-dependent manner indicating that oxidative stress has adverse effects on DENV infection. ROS affects early stages of DENV replication as observed by quantitation of positive and negative strand viral RNA. We observed that addition of ROS specifically affected viral titres of positive strand RNA viruses. We further demonstrate that ROS specifically altered SEC31A expression at the ER suggesting a role for SEC31A-mediated pathways in the life-cycle of positive strand RNA viruses and provides an opportunity to identify drug targets regulating oxidative stress responses for antiviral development.

中文翻译：

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氧化应激特异性抑制登革热病毒的复制

活性氧 (ROS) 是化学活性物质，参与维持生理浓度的细胞和信号过程。因此，调节氧化还原平衡的细胞成分可能在病毒生命周期中发挥关键作用，无论是作为病毒复制的促进剂还是具有抗病毒功能。锌是一种与抗氧化系统相关的必需微量营养素，有助于维持平衡的细胞氧化还原状态。在这里，我们表明锌螯合导致上皮细胞中活性氧 (ROS) 的诱导，并且锌的添加将 ROS 水平恢复到基础状态。添加 ROS (H 2 O 2) 以剂量依赖性方式抑制登革热病毒 (DENV) 感染，表明氧化应激对 DENV 感染有不利影响。通过正链和负链病毒 RNA 的定量观察到，ROS 影响 DENV 复制的早期阶段。我们观察到添加 ROS 特别影响正链 RNA 病毒的病毒滴度。我们进一步证明 ROS 特异性地改变了 ER 处的 SEC31A 表达，表明 SEC31A 介导的途径在正链 RNA 病毒的生命周期中发挥作用，并提供了一个机会来确定调节氧化应激反应以进行抗病毒发展的药物靶点。