State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China.
Viruses. 2020 Jul 14;12(7):756. doi: 10.3390/v12070756.
Enterovirus 71 (EV71) is the main pathogen causing hand-foot-mouth disease (HFMD) in infants and children, which can also lead to severe neurological diseases and even death. Therefore, understanding the replication mechanism of EV71 is of great significance for the prevention and control of EV71-induced diseases. Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) is an important core protein for the initiation and the normal process of autophagy in cells. In addition to its involvement in autophagy, Beclin1 has also been reported to play an important role in cancer and innate immune signaling pathways. However, the role of Beclin1 in EV71 replication remains elusive. Here, we primarily found that Beclin1 facilitates EV71 replication in human rhabdomyosarcoma (RD) cells and the autophagy was actually induced, but Beclin1 was not significantly affected at either mRNA level or protein level during early EV71 infection. Further studies discovered that Beclin1 could interacts with EV71 non-structural protein 3D mainly through its evolutionary conserved domain (ECD) and coiled-coiled domain (CCD), thus promoting the replication of EV71 in human rhabdomyosarcoma (RD) cells and human astroglioma (U251) cells. Collectively, we reveal a novel regulatory mechanism associated with Beclin1 to promote EV71 replication, thus providing a potential therapeutic target for the prevention and control of EV71-associated diseases.
肠道病毒 71 型（EV71）是引起婴幼儿手足口病（HFMD）的主要病原体，可导致严重的神经系统疾病，甚至死亡。因此，了解 EV71 的复制机制对于预防和控制 EV71 引起的疾病具有重要意义。Beclin1（BECN1，酵母中 ATG6 的哺乳动物同源物）是细胞自噬起始和正常过程的重要核心蛋白。除了参与自噬外，Beclin1 还被报道在癌症和先天免疫信号通路中发挥重要作用。然而，Beclin1 在 EV71 复制中的作用仍不清楚。在这里，我们主要发现 Beclin1 促进人横纹肌肉瘤（RD）细胞中的 EV71 复制，并且实际上诱导了自噬，但在 EV71 感染早期，Beclin1 的 mRNA 水平或蛋白水平没有明显变化。进一步的研究发现，Beclin1 可以通过其进化保守结构域（ECD）和卷曲螺旋结构域（CCD）与 EV71 非结构蛋白 3D 相互作用，从而促进 EV71 在人横纹肌肉瘤（RD）细胞和人神经胶质瘤（U251）细胞中的复制。总之，我们揭示了一种与 Beclin1 相关的新型调节机制，以促进 EV71 的复制，从而为预防和控制 EV71 相关疾病提供了一个潜在的治疗靶点。
