热休克蛋白HSP60参与口蹄疫病毒形态发生的作用及其机制

形态发生是病毒生命周期的重要环节，揭示病毒如何利用宿主蛋白完成病毒衣壳组装及粒子成熟的形态发生过程，对理解病毒分子致病机理至关重要。前期研究中发现，热休克蛋白HSP60与口蹄疫病毒（FMDV）衣壳蛋白共存，为了明确HSP60参与FMDV形态发生的具体机制，本研究将从FMDV粒子形成的几个环节（衣壳蛋白前体P1裂解，5s原体、12s五聚体、75s空衣壳及146s完整病毒的形成）入手，利用HSP60抑制剂及FMDV药物耐受突变株，分别从细胞、细菌、无细胞表达系统、动物体内等不同层面，采用蔗糖密度梯度离心、尺寸排阻色谱、非放射性免疫标记等技术，全方位追踪HSP60介入病毒衣壳组装的调控细节及分子作用机理，为揭示病毒感染机制提供研究数据，也为解决病毒样颗粒疫苗体外组装效率提升的技术问题、寻求潜在作用靶点以设计抗小RNA病毒广谱药物等奠定理论基础。

Morphogenesis is an important part of the virus's life cycle, tracking how the foot-and-mouth disease virus (FMDV) uses host proteins for viral capsid assembly and particle maturation is crucial to understanding the mechanism of viral infection. Previous studies found that the molecular chaperone HSP60 was stably bound to the capsid protein of foot-and-mouth disease virus (FMDV), and then it was preliminarily confirmed that HSP60 was related to the proliferation of FMDV. In order to determine whether HSP60 is involved in FMDV morphogenesis and clarify the specific mechanism, this study will start from several stages of FMDV morphogenesis (the cleavage of capsid protein precursor P1, the formation of 5s protomer, 12s pentamer, 75s empty capsid and 146s intact virus), using HSP60 inhibitors and anti-inhibitor FMDV mutation, respectively, to discuss the role and mechanism of HSP60 in regulating the capsid assembly of FMDV from different level including the cells, bacteria, the cell-free protein synthesis system, and living animal. The results will provide the research data to infection mechanism of morphogenesis. It also provides theoretical guidance to solve the technical problem of improving the assembly efficiency of virus-like particles (VLPs) vaccine in vitro and to provide potential targets for designing broad-spectrum drugs against small RNA viruses.