Sec62 Regulates Endoplasmic Reticulum Stress and Autophagy Balance to Affect Foot-and-Mouth Disease Virus Replication

文献类型： 外文期刊

第一作者： Wu, Jin'en

作者： Wu, Jin'en;Zhang, Zhihui;Teng, Zhidong;Abdullah, Sahibzada Waheed;Sun, Shiqi;Guo, Huichen;Wu, Jin'en;Zhang, Zhihui;Teng, Zhidong;Abdullah, Sahibzada Waheed;Sun, Shiqi;Guo, Huichen;Guo, Huichen

作者机构：

关键词： FMDV; ER stress; autophagy; Sec62; UPR

期刊名称：FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY （ 影响因子：5.293； 五年影响因子：5.882 ）

ISSN： 2235-2988

年卷期： 2021 年 11 卷

页码：

收录情况： SCI

摘要： Endoplasmic reticulum (ER) stress-induced autophagy is closely associated with viral infection and propagation. However, the intrinsic link between ER stress, autophagy, and viral replication during foot-and-mouth disease virus (FMDV) infection is not fully elucidated. Our previous studies demonstrated that FMDV infection activated the ER stress-associated UPR of the PERK-eIF2a and ATF6 signaling pathway, whereas the IRE1a signaling was suppressed. We found that the activated-ATF6 pathway participated in FMDV-induced autophagy and FMDV replication, while the IRE1 alpha pathway only affected FMDV replication. Further studies indicated that Sec62 was greatly reduced in the later stages of FMDV infection and blocked the activation of the autophagy-related IRE1 alpha-JNK pathway. Moreover, it was also found that Sec62 promoted IRE1a phosphorylation and negatively regulated FMDV proliferation. Importantly, Sec62 may interact with LC3 to regulate ER stress and autophagy balance and eventually contribute to FMDV clearance via fusing with lysosomes. Altogether, these results suggest that Sec62 is a critical molecule in maintaining and recovering ER homeostasis by activating the IRE1 alpha-JNK pathway and delivering autophagosome into the lysosome, thus providing new insights on FMDV-host interactions and novel antiviral therapies.

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