小RNA病毒感染与致病机制的结构基础

项目名称： 小RNA病毒感染与致病机制的结构基础

项目编号： No.81330036

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 饶子和

作者单位： 清华大学

项目金额： 310万元

中文摘要： 小RNA病毒（Picornaviridae）是一类能够引起多种人类严重传染性疾病的病原体。小RNA病毒生命周期可以分为入侵（包括受体识别和解包被两个环节）、转录与复制、组装与释放等核心步骤，其中的入侵过程是病毒感染与致病的关键步骤。虽然小RNA病毒各个成员的结构蛋白的同源性较高，但其受体识别和解包被过程具有极大的区别。本项目选择小RNA病毒为研究对象，特别是造成严重疫情的手足口病病毒、甲型肝炎病毒等代表种属，以“病毒入侵”这一小RNA病毒生命周期中的关键步骤为切入点，重点关注小RNA病毒入侵过程中“受体识别”和“解包被”两个核心环节，发现受体识别的分子机制，揭示解包被过程中病毒颗粒的动态结构，阐明不同小RNA病毒感染与致病机制的异同和规律，提出阻断小RNA病毒入侵过程的有效策略，为抗病毒药物和疫苗的研制提供关键的生物学基础。

中文关键词： 小RNA病毒;受体;入侵;三维结构;动态变化

英文摘要： Picornavirus constitutes a large family of non-enveloped positive-sense single stranded RNA (+ssRNA) virus. Picornavirus is one of the most important model organisms to study the fundamental virology questions, including the discovery of RNA-dependant RNA polymerase, X-ray structural virology, etc. Moreover, numbers of pathogens to cause severe human infection diseases are classified in Picornaviridae family. The entire lifecycle of picornavirus can be featured as entry, transcription and replication, assembly and release. Entry, which could be further subdivided to receptor recognition and uncoating processes, is the first key step of picornaviral lifecycle. Although the structural proteins encoded by picornaviruses share primary sequence and structural homologies, the mechanisms for receptor recognition and uncoating of those picornaviruses are distinct. In this study, we will solve the three-dimensional structures of major antigen VP1 and the matured virus particle in complex with different receptors to elucidate the mechanism of receptor recognition of different picornavirus, in particular, EV71, CVA16 and HAV. We will also solve the dynamic structures of virus particles during uncoating process to elucidate the molecular mechanism of picornaviral uncoating. These results will provide the great potential to discover the antiviral therapeutics targeting at picornavirus.

英文关键词： picornavirus;receptor;entry;structure;dynamic