The Golgi protein ACBD3 facilitates Enterovirus 71 replication by interacting with 3A.
The Golgi protein ACBD3 facilitates Enterovirus 71 replication by interacting with 3A.
复制标题
高尔基体蛋白 ACBD3 通过与 3A 相互作用促进肠道病毒 71 复制。
DOI：
10.1038/srep44592
复制
发表时间：
2017-03-17
影响因子：
4.6
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Lei X;Xiao X;Zhang Z;Ma Y;Qi J;Wu C;Xiao Y;Zhou Z;He B;Wang J
肠道病毒71（EV71）是一种人类病原体，可引起手足口病和神经系统并发症。尽管EV71以及其他肠道病毒启动细胞内膜的重塑以进行基因组复制，但调控机制仍然难以捉摸。通过对人cDNA文库的筛选，我们发现高尔基体蛋白酰基辅酶A结合域3（ACBD 3）是EV71病毒3A蛋白的靶蛋白。这种相互作用发生在表达3A或感染EV71的细胞中。ACBD3的遗传抑制或缺失显著损害病毒RNA复制和噬斑形成。这些缺陷在ACBD 3恢复后得到纠正。在感染的细胞中，EV71 3A将ACBD 3重定向至复制位点。3A中的I44A或H54Y取代中断与ACBD 3的结合。因此，病毒复制受到阻碍。这些结果揭示了涉及宿主ACBD 3的EV71复制机制。
Enterovirus 71 (EV71) is a human pathogen that causes hand, foot, mouth disease and neurological complications. Although EV71, as well as other enteroviruses, initiates a remodeling of intracellular membrane for genomic replication, the regulatory mechanism remains elusive. By screening human cDNA library, we uncover that the Golgi resident protein acyl-coenzyme A binding domain-containing 3 (ACBD3) serves as a target of the 3A protein of EV71. This interaction occurs in cells expressing 3A or infected with EV71. Genetic inhibition or deletion of ACBD3 drastically impairs viral RNA replication and plaque formation. Such defects are corrected upon restoration of ACBD3. In infected cells, EV71 3A redirects ACBD3, to the replication sites. I44A or H54Y substitution in 3A interrupts the binding to ACBD3. As such, viral replication is impeded. These results reveal a mechanism of EV71 replication that involves host ACBD3 for viral replication.