高尔基蛋白 ACBD3 通过与 3A 相互作用促进肠道病毒 71 的复制。

The Golgi protein ACBD3 facilitates Enterovirus 71 replication by interacting with 3A.

机构信息

MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing P.R. China.

Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, United States of America.

出版信息

Sci Rep. 2017 Mar 17;7:44592. doi: 10.1038/srep44592.

DOI:10.1038/srep44592

PMID:28303920

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5356004/

Abstract

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.

摘要

肠道病毒 71 型（EV71）是一种引起手足口病和神经并发症的人类病原体。尽管 EV71 以及其他肠道病毒会启动细胞内膜的重塑以进行基因组复制，但调节机制仍不清楚。通过筛选人 cDNA 文库，我们发现高尔基驻留蛋白酰基辅酶 A 结合域包含蛋白 3（ACBD3）是 EV71 的 3A 蛋白的靶标。这种相互作用发生在表达 3A 蛋白的细胞或感染 EV71 的细胞中。ACBD3 的遗传抑制或缺失会严重损害病毒 RNA 复制和斑块形成。在恢复 ACBD3 后，这些缺陷得到纠正。在感染细胞中，EV71 3A 将 ACBD3 重定向到复制部位。3A 中的 I44A 或 H54Y 取代会中断与 ACBD3 的结合。因此，病毒复制受到阻碍。这些结果揭示了 EV71 复制的一种机制，该机制涉及宿主 ACBD3 进行病毒复制。