Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan.
Healthy Aging Research Center, Chang Gung University, Taoyuan City 33302, Taiwan.
Viruses. 2022 Aug 4;14(8):1717. doi: 10.3390/v14081717.
Enterovirus (EV) 71 caused episodes of outbreaks in China and Southeast Asia during the last few decades. We have previously reported that EV71 induces reactive oxygen species (ROS). However, the underlying mechanism remains elusive. Co-immunoprecipitation-proteomic analysis revealed that enteroviral 2B protein interacted with mitochondrial voltage-dependent anion channel 3 (VDAC3). Knockdown (KD) of expression specifically inhibited enteroviral replication. Single-round viral replication was also inhibited in KD cells, suggesting that VDAC3 plays an essential role in replication. Consistent with this, gene KD significantly reduced the EV71-induced mitochondrial ROS generation. Exogenous 2B expression could induce the mitochondrial ROS generation that was significantly reduced in -KD cells or in the Mito-TEMPO-treated cells. Moreover, VDAC3 appears to be necessary for regulation of antioxidant metabolism. gene KD led to the enhancement of such pathways as hypotaurine/taurine synthesis in the infected cells. Taken together, these findings suggest that 2B and VDAC3 interact to enhance mitochondrial ROS generation, which promotes viral replication.
肠道病毒 (EV) 71 在过去几十年中在中国和东南亚引发了多次爆发。我们之前曾报道过 EV71 诱导活性氧 (ROS)。然而，其潜在机制仍不清楚。共免疫沉淀蛋白质组学分析显示，肠道病毒 2B 蛋白与线粒体电压依赖性阴离子通道 3 (VDAC3) 相互作用。表达的特异性敲低 (KD) 特别抑制了肠道病毒的复制。在 KD 细胞中，单轮病毒复制也受到抑制，这表明 VDAC3 在复制中起着至关重要的作用。与此一致，基因 KD 显著降低了 EV71 诱导的线粒体 ROS 生成。外源性 2B 表达可诱导线粒体 ROS 的产生，而在 -KD 细胞或 Mito-TEMPO 处理的细胞中，这种产生显著减少。此外，VDAC3 似乎是调节抗氧化代谢所必需的。基因 KD 导致感染细胞中类似牛磺酸/半胱氨酸合成等途径的增强。综上所述，这些发现表明 2B 和 VDAC3 相互作用以增强线粒体 ROS 的产生，从而促进病毒复制。
