Jiangxi Provincial Key Laboratory of Systems Biomedicine, Jiujiang University, Jiujiang, China.
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
Microb Pathog. 2024 May;190:106638. doi: 10.1016/j.micpath.2024.106638. Epub 2024 Apr 2.
Autophagy plays an important role in the lifecycle of viruses. However, there is currently a lack of systematic research on the relationship between Infectious Bronchitis Virus (IBV) and autophagy. This study aims to investigate the impact of IBV on autophagy and the role of autophagy in viral replication. We observed that IBV infection increased the expression of microtubule-associated protein 1 light chain 3, a marker of autophagy, decreased the expression of sequestosome 1, and led to elevated intracellular LC3 puncta levels. These findings suggest that IBV infection activates the autophagic process in cells. To investigate the impact of autophagy on the replication of IBV, we utilized rapamycin as an autophagy activator and 3-methyladenine as an autophagy inhibitor. Our results indicate that IBV promotes viral replication by inducing autophagy. Further investigation revealed that IBV induces autophagosome formation by inhibiting the mTOR-ULK1 pathway and activating the activity of vacuolar protein sorting 34 (VPS34), autophagy-related gene 14, and the Beclin-1 complex. VPS34 plays a crucial role in this process, as inhibiting VPS34 protein activity enhances cell proliferation after IBV infection. Additionally, inhibiting VPS34 significantly improves the survival rate of IBV-infected chicks, suppresses IBV replication in the kidney, and alleviates tracheal, lung, and kidney damage caused by IBV infection. In summary, IBV infection can induce autophagy by modulating the mTOR/ULK1 signaling pathway and activating the VPS34 complex, while autophagy serves to promote virus replication.
自噬在病毒的生命周期中起着重要作用。然而,目前对于传染性支气管炎病毒(IBV)与自噬之间的关系还缺乏系统的研究。本研究旨在探讨 IBV 对自噬的影响以及自噬在病毒复制中的作用。我们观察到,IBV 感染会增加微管相关蛋白 1 轻链 3 的表达,这是自噬的一个标志物,同时会降低自噬体相关蛋白 1 的表达,导致细胞内 LC3 斑点水平升高。这些发现表明,IBV 感染会激活细胞中的自噬过程。为了研究自噬对 IBV 复制的影响,我们利用雷帕霉素作为自噬激活剂和 3-甲基腺嘌呤作为自噬抑制剂。结果表明,IBV 通过诱导自噬来促进病毒复制。进一步的研究表明,IBV 通过抑制 mTOR-ULK1 信号通路和激活液泡蛋白分选 34(VPS34)、自噬相关基因 14 和 Beclin-1 复合物来诱导自噬体的形成。VPS34 在这个过程中起着关键作用,因为抑制 VPS34 蛋白的活性可以增强 IBV 感染后细胞的增殖。此外,抑制 VPS34 显著提高了 IBV 感染雏鸡的存活率,抑制了 IBV 在肾脏中的复制,并减轻了 IBV 感染引起的气管、肺和肾脏损伤。综上所述,IBV 感染可以通过调节 mTOR/ULK1 信号通路和激活 VPS34 复合物来诱导自噬,而自噬则有助于促进病毒复制。