Enterovirus A71 (EV-A71 or EV-71) is an RNA virus that causes hand, foot and mouse disease in children. The N6-methyladenosine (m6A) of RNA is a common RNA modification involved in various biological events. METTL3 is an m6A methyltransferase that regulates EV-71 replication. EV-71 infection induces autophagy, which also promotes EV-71 replication. In this study, we explored the role of METTL3 in EV-71 infection-induced autophagy. We constructed lentivirus expressing METTL3-specific shRNA and knocked down the endogenous METTL3 in mouse Schwann cells. We infected normal Schwann cells and METTL3 knockdown Schwann cells and compared the viral titer, expression of autophagy-related proteins and apoptosis-related protein. Transduction of lentivirus expressing METTL3 shRNA significantly decreased the endogenous METTL3. Knocking down METTL3 decreased the viral titer of EV-71 after infection. Knocking down METTL3 prevented EV-71-induced cell death and suppressed EV-71-induced expression of Bax while rescuing Bcl-2 expression after EV-71 infection. Knocking down METTL3 inhibited EV-71-induced expression of Atg5, Atg7 and LC3 II. Knocking down METTL3 inhibited EV-71-induced apoptosis and autophagy. In summary, our study describes the relationship of METTL3 and autophagy during EV-71 infection.

中文翻译：

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敲除 METTL3 通过调节自噬抑制肠道病毒 71 诱导的小鼠雪旺细胞凋亡

肠道病毒 A71（EV-A71 或 EV-71）是一种 RNA 病毒，可导致儿童手足和小鼠疾病。RNA 的 N6-甲基腺苷 (m6A) 是一种常见的 RNA 修饰，涉及各种生物事件。METTL3 是一种调节 EV-71 复制的 m6A 甲基转移酶。EV-71 感染诱导自噬，这也促进 EV-71 复制。在本研究中，我们探讨了 METTL3 在 EV-71 感染诱导的自噬中的作用。我们构建了表达 METTL3 特异性 shRNA 的慢病毒，并在小鼠雪旺细胞中敲低了内源性 METTL3。我们感染了正常的雪旺细胞和 METTL3 敲低的雪旺细胞，并比较了病毒滴度、自噬相关蛋白和凋亡相关蛋白的表达。转导表达 METTL3 shRNA 的慢病毒显着降低了内源性 METTL3。击倒 METTL3 会降低感染后 EV-71 的病毒滴度。敲除 METTL3 可防止 EV-71 诱导的细胞死亡并抑制 EV-71 诱导的 Bax 表达，同时在 EV-71 感染后挽救 Bcl-2 表达。敲除 METTL3 可抑制 EV-71 诱导的 Atg5、Atg7 和 LC3 II 的表达。敲除 METTL3 可抑制 EV-71 诱导的细胞凋亡和自噬。总之，我们的研究描述了 EV-71 感染期间 METTL3 与自噬的关系。