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 IRE1α 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 IRE1α-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 IRE1α-JNK pathway and delivering autophagosome into the lysosome, thus providing new insights on FMDV-host interactions and novel antiviral therapies.

中文翻译：

---

Sec62 调节内质网应激和自噬平衡以影响口蹄疫病毒复制。

内质网（ER）应激诱导的自噬与病毒感染和传播密切相关。然而，口蹄疫病毒 (FMDV) 感染期间 ER 应激、自噬和病毒复制之间的内在联系尚未完全阐明。我们之前的研究表明，FMDV 感染激活了 PERK-eIF2a 和 ATF6 信号通路的 ER 应激相关 UPR，而 IRE1a 信号传导被抑制。我们发现激活的 ATF6 通路参与 FMDV 诱导的自噬和 FMDV 复制，而 IRE1α 通路仅影响 FMDV 复制。进一步的研究表明，Sec62 在 FMDV 感染的后期大大减少，并阻断了自噬相关的 IRE1α-JNK 通路的激活。而且，还发现Sec62促进IRE1a磷酸化并负调节FMDV增殖。重要的是，Sec62 可能与 LC3 相互作用以调节 ER 应激和自噬平衡，并最终通过与溶酶体融合促进 FMDV 清除。总之，这些结果表明，Sec62 是维持和恢复 ER 稳态的关键分子，通过激活 IRE1α-JNK 通路并将自噬体递送到溶酶体中，从而为 FMDV 宿主相互作用和新型抗病毒疗法提供新的见解。