Clinical and Cellular Virology lab, Infection and Immunology, Translational Health Science and Technology Institute, Faridabad, Haryana, India.
Employees State Insurance Corporation Medical College and Hospital, Faridabad, Haryana, India.
J Gen Virol. 2021 Apr;102(4). doi: 10.1099/jgv.0.001596.
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 (HO) 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.
活性氧 (ROS) 是一种化学活性物质，参与维持生理浓度下的细胞和信号转导过程。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，无论是作为促进病毒复制的因素还是具有抗病毒功能的因素。锌是一种与抗氧化系统相关的必需微量元素，有助于维持细胞内的氧化还原平衡状态。在这里，我们发现锌螯合作用导致上皮细胞中活性氧 (ROS) 的诱导，并且添加锌将 ROS 水平恢复到基础状态。ROS（HO）的添加以剂量依赖性方式抑制登革热病毒 (DENV) 的感染，表明氧化应激对 DENV 感染有不利影响。ROS 影响 DENV 复制的早期阶段，如正链和负链病毒 RNA 的定量所示。我们观察到 ROS 的添加特异性影响正链 RNA 病毒的病毒效价。我们进一步证明 ROS 特异性地改变内质网 (ER) 中的 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，并为识别调节氧化应激反应的抗病毒药物靶点提供了机会。
