Peng Qiuyan, Liu Guangming, Zhu Danping, Li Suyun, Yang Sida, Li Peiqing, Yin Yingxian, Hu Dandan
Jinan University, #601, Huangpu Avenue West, Guangzhou 510632, Guangdong, PR China.
Pediatric Emergency Department, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, PR China.
Virus Res. 2025 Jun 4;358:199590. doi: 10.1016/j.virusres.2025.199590.
Enterovirus 71 (EV71) is one of the enteroviruses that causes hand-foot-and-mouth disease (HFMD). This study aims to investigate the role of EV71 structural viral protein 1 (VP1) in mouse Schwann cells.
An EV71 VP1-expressing vector was generated and transfected into mouse Schwann cells (MSCs). Small interfering RNAs against methyltransferase-like protein 14 (METTL14) and YTH N-Methyladenosine RNA Binding Protein 1 (YTHDF1) were used to knock down the expressions of METTL14 and YTHDF1 in MSCs to investigate their roles in peripheral myelin protein 22 (PMP22) expression. Real-time PCR and Western blot analysis were performed to determine the expressions of PMP22 and mA modification-associated proteins.
EV71-VP1 over-expression significantly increased the expressions of transmethylase METTL3/14 and mA methylation recognition protein YTHDC1 and YTHDF1/2/3 in MSCs. On the contrary, the level of demethylase FTO, but not ALKBH5, was obviously decreased in VP1-over-expressed MSCs. Furthermore, 3-DZA inhibited expressions of METTL3/14 and YTHDF1/2 in VP1-over-expressed MSCs, indicating METTL3/14 and YTHDF1/2 were the key mA-modification-related genes regulated by VP1. In addition, deficiency of METTL14 or YTHDF1 contracted the up-regulation of PMP22 induced by VP1 overexpression in MSCs.
VP1 up-regulated PMP22 via m6A modification in MSCs, which were mainly affected by METTL14 and YTHDF1.
肠道病毒71型（EV71）是引起手足口病（HFMD）的肠道病毒之一。本研究旨在探讨EV71病毒结构蛋白1（VP1）在小鼠雪旺细胞中的作用。
构建表达EV71 VP1的载体并转染至小鼠雪旺细胞（MSCs）。使用针对甲基转移酶样蛋白14（METTL14）和YTH N-甲基腺苷RNA结合蛋白1（YTHDF1）的小干扰RNA敲低MSCs中METTL14和YTHDF1的表达，以研究它们在外周髓鞘蛋白22（PMP22）表达中的作用。进行实时定量PCR和蛋白质免疫印迹分析以确定PMP22和m⁶A修饰相关蛋白的表达。
EV71-VP1过表达显著增加了MSCs中甲基转移酶METTL3/14和m⁶A甲基化识别蛋白YTHDC1以及YTHDF1/2/3的表达。相反，在VP1过表达的MSCs中，去甲基化酶FTO的水平明显降低，而ALKBH5的水平未降低。此外，3-脱氮杂腺苷（3-DZA）抑制了VP1过表达的MSCs中METTL3/14和YTHDF1/2的表达，表明METTL3/14和YTHDF1/2是受VP1调控的关键m⁶A修饰相关基因。此外，METTL14或YTHDF1的缺失抑制了VP1过表达诱导的MSCs中PMP22的上调。
VP1通过m⁶A修饰上调MSCs中PMP22的表达，这一过程主要受METTL14和YTHDF1影响。
