小RNA病毒感染与致病机制的结构基础

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.

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。

小RNA病毒（Picornaviridae）是典型的无囊膜、单股正链RNA病毒. 并且，小RNA病毒家族包含大量引起人类严重传染性疾病的病原体。小RNA病毒的生命周期包括入侵，转录和复制，组装和释放。入侵过程也可被进一步细分为受体识别和脱衣壳。本项目选择小RNA病毒为研究对象，重点关注病毒入侵过程中“受体识别”和“脱衣壳”两个核心环节的三维结构，发现受体识别的分子机制，揭示基因组释放过程中病毒颗粒的动态过程，阐明不同小RNA病毒科成员入侵机制的异同和规律，尤其是针对EV71,CVA16以及HAV病毒。研究成果为解决“小RNA病毒感染与致病机制”提供了科学依据，也为抗病毒药和疫苗的研制提供了关键的生物学基础。