Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication
Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication
复制标题
Beclin1 与肠道病毒 71 3D 蛋白结合促进病毒复制
DOI：
10.3390/v12070756
复制
发表时间：
2020-07
期刊：
影响因子：
4.7
通讯作者：
Wu Jianguo
中科院分区：
文献类型：
--
作者：
Xiang Qi;Wan Pin;Yang Ge;Huang Siyu;Qin Mengying;Yang Hua;Luo Zhen;Wu Kailang;Wu Jianguo
肠病毒71型（EV71）是引起婴幼儿手足口病的主要病原体，还可导致严重的神经系统疾病甚至死亡。因此，了解EV71的复制机制对预防和控制EV71诱导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，据报道Beclin1也在癌症和先天免疫信号通路中发挥重要作用。然而，Beclin1在EV71复制中的作用仍然难以捉摸。本研究主要发现Beclin1促进了EV71在人横纹肌肉瘤（RD）细胞中的复制，并诱导了细胞的自噬，但在EV71感染的早期，Beclin1在mRNA水平和蛋白水平上均未受到显著影响。进一步研究发现Beclin1主要通过其进化保守结构域（ECD）和螺旋结构域（CCD）与EV71非结构蛋白3D相互作用，从而促进EV71在人横条肌肉瘤（RD）细胞和人星形胶质瘤（U251）细胞中的复制。总之，我们揭示了与Beclin1相关的促进EV71复制的新调控机制，从而为预防和控制EV71相关疾病提供了潜在的治疗靶点。
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.
登录
查看更多内容
柯萨奇病毒 B3 的细胞毒性与突触蛋白 17 表达减少介导的自噬流阻断有关
影响因子：
9
作者：
Tian L;Yang Y;Li C;Chen J;Li Z;Li X;Li S;Wu F;Hu Z;Yang Z
通讯作者：
Yang Z
影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
影响因子：
5.4
作者：
Changzhi Xu;Xiang He;Zirui Zheng;Zhe Zhang;Congwen Wei;K. Guan;L. Hou;Buchang Zhang;Lin Zhu-Li
通讯作者：
Changzhi Xu;Xiang He;Zirui Zheng;Zhe Zhang;Congwen Wei;K. Guan;L. Hou;Buchang Zhang;Lin Zhu-Li
影响因子：
13.3
作者：
Furuya, Norihiko;Yu, Jie;Levine, Beth
通讯作者：
Levine, Beth
影响因子：
4.8
作者：
Shibata, Mamoru;Lu, Tao;Yuan, Junying
通讯作者：
Yuan, Junying