高尔基体ACBD3蛋白复合物参与EV71复制的分子机制研究

肠道病毒71型（EV71）属于小RNA病毒科，是引起重症手足口病的主要病原体，但其感染复制机制尚未阐明。通过病毒EV71编码各非结构蛋白与宿主因子的相互作用组筛选，我们发现高尔基体蛋白ACBD3可与病毒非结构蛋白3A相互作用并通过病毒感染实验予以确认，且发现该蛋白是EV71复制所需的，而病毒感染可改变其在细胞内的分布，但ACBD3参与EV71复制的精细分子机制尚不清楚。鉴此，本课题拟在前期发现的基础上，以ACBD3与3A相互作用的分子机制为切入点，进一步分析这种相互作用对于病毒复制所需的宿主因子募集至病毒复制中心的影响，以及该复合物募集至病毒复制中心对于脂类物质生成、运输及分布的调控。以期从宿主内膜复合物入手初步揭示ACBD3复合物与EV71复制的调控关系及分子机制，为阐明病毒致病机理提供科学依据。

Enterovirus 71 (EV71), belonging to the family of the picornaviridae, is the major causative pathogen of hand-foot-and-mouth disease (HFMD). However, the molecular mechanisms of EV71 replication are elusive. Our preliminary results showed that EV71 3A protein interacts with ACBD3. Furthermore, EV71 replication was inhibited when cell transfected with siRNA against ACBD3, suggesting that ACBD3 participated in the replication of EV71. Furthermore, upon EV71 infection, ACBD3 was dispersed into the cytosol and co-localizated with 3A. Based on the above findings, this project is going to further analysis the roles and molecular mechanisms of the ACBD3 complex involved in EV71 replication. We will investigate which domains or amino acids are responsible for the interaction between ACBD3 and 3A, and whether the interaction promotes the recruitment of host factors, which are needed for EV71 replication, to RNA replication centers. Further, we are going to clarify the effects of the complex on lipid production and transmission. As such, our project will provide the theoretical basis for the elucidation of pathogenesis of EV71.