Jung Kwang Il, Pyo Chul Woong, Choi Sang-Yun
Department of Life Sciences, Korea University, Seoul 136-701, South Korea.
Department of Life Sciences, Korea University, Seoul 136-701, South Korea.
Biochem Biophys Res Commun. 2018 Apr 15;498(4):960-966. doi: 10.1016/j.bbrc.2018.03.089. Epub 2018 Mar 17.
Infection with influenza A virus (IAV) A/WSN/1933 (H1N1) causes oxidative stress and severe lung injury. We have demonstrated that the generation of reactive oxygen species (ROS) during IAV infection is tightly regulated by superoxide dismutase 1 (SOD1) and correlated with viral replication in alveolar epithelial cells. However, the molecular mechanism underlying SOD1 reduction during IAV infection is uncertain. Here we demonstrate that the autophagy pathway is activated by IAV infection and involved in enhanced ROS generation in the early phase of infection. We observed that IAV infection induced autophagic vacuolation, leading to autophagic degradation of cellular proteins, including the protease sensitive antioxidant SOD1. Silencing of the microtubule-associated protein 1A/1B-light chain 3 (LC3) gene in A549 cells supported the critical role of autophagy in the ROS increase. The decrease in viral titer and viral polymerase activity caused by LC3 silencing or the autophagy inhibitor clearly evidenced the involvement of autophagy in the control of ROS generation and viral infectivity. Therefore, we concluded that early stage IAV infection induces autophagic degradation of antioxidant enzyme SOD1, thereby contributing to increased ROS generation and viral infectivity in alveolar epithelial cells.
感染甲型流感病毒（IAV）A/WSN/1933（H1N1）会导致氧化应激和严重的肺损伤。我们已经证明，IAV感染期间活性氧（ROS）的产生受到超氧化物歧化酶1（SOD1）的严格调控，并且与肺泡上皮细胞中的病毒复制相关。然而，IAV感染期间SOD1减少的分子机制尚不清楚。在此，我们证明自噬途径被IAV感染激活，并参与感染早期ROS的产生增加。我们观察到IAV感染诱导自噬空泡化，导致细胞蛋白质包括蛋白酶敏感的抗氧化剂SOD1的自噬降解。在A549细胞中沉默微管相关蛋白1A/1B轻链3（LC3）基因支持了自噬在ROS增加中的关键作用。由LC3沉默或自噬抑制剂引起的病毒滴度和病毒聚合酶活性的降低清楚地证明了自噬参与了ROS产生的控制和病毒感染性。因此，我们得出结论，IAV感染早期诱导抗氧化酶SOD1的自噬降解，从而导致肺泡上皮细胞中ROS产生增加和病毒感染性增强。
