Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing, 100097, China.
College of Animal Husbandry and Veterinary Medicine, Xinyang Agriculture and Forestry University, Xinyang, 464000, China.
Virology. 2019 Nov;537:254-263. doi: 10.1016/j.virol.2019.08.029. Epub 2019 Aug 30.
Diverse effects on autophagy, a cell degradation pathway, have been associated with the infectious mechanisms of different pathogens. Here, we demonstrated that Seneca valley virus (SVV), an important emerging porcine virus characterized by vesicular lesions and neonatal mortality, can induce autophagy in cultured PK-15 and BHK-21 cells by detecting autophagosome formation, GFP-LC3 puncta and accumulation of LC3-II proteins. Treatment with pharmacological inducers/inhibitors and small interfering RNA sequences targeting genes critical for autophagosome formation affected autophagy induction and viral yields. SVV induced a complete autophagic process to enhance its replication. The PERK and ATF6 pathways, two components of the endoplasmic reticulum (ER)-related unfolded protein response (UPR), were also activated in SVV-infected cells and downregulation of their expression suppressed SVV-induced autophagy and viral yields. Overall, these results reveal that SVV induces autophagy in cultured cells through the PERK and ATF6 pathways, thereby contributing to understanding of the molecular mechanisms underlying SVV pathogenesis.
不同的病原体通过不同的感染机制对细胞降解途径自噬产生多种影响。在这里，我们通过检测自噬体的形成、GFP-LC3 斑点和 LC3-II 蛋白的积累，证明了 SVV（一种以囊泡病变和新生仔猪死亡为特征的重要新兴猪病毒）可以诱导培养的 PK-15 和 BHK-21 细胞发生自噬。用针对自噬体形成关键基因的药理学诱导剂/抑制剂和小干扰 RNA 序列处理会影响自噬的诱导和病毒产量。SVV 诱导完整的自噬过程以增强其复制。内质网（ER）相关未折叠蛋白反应（UPR）的两个组成部分 PERK 和 ATF6 通路也在感染 SVV 的细胞中被激活，下调其表达会抑制 SVV 诱导的自噬和病毒产量。总的来说，这些结果表明，SVV 通过 PERK 和 ATF6 通路诱导培养细胞中的自噬，从而有助于理解 SVV 发病机制的分子机制。
