对虾白斑症病毒感染和囊膜组装相关蛋白的结构和功能研究

White spot syndrome virus (WSSV) is one of the major and most serious pathogen in the shrimp farming industry. WSSV has a wide host range. The virulence of WSSV is very high, resulting in mortality rates from 90 to 100% within 3 to 7 days of infection and leading to billions of dollars economic loss each year in the shrimp farming industry. So far, there is no effective strategy to prevent and control the virus, and little is known about their infection pathogenic mechanism. The structural and functional studies of the viral proteins associated with the WSSV assembly and infection will provide significant information for revealing the mechanisms of WSSV assembly and infection, and the valuable theoretical and practical knowledge for the inhibitor design based on WSSV envelope assembly and infection. Therefore, we focus on the structural and functional analysis of viral proteins, such as envelope protein VP19、VP24、nucleocapsid protein VP51C and protein complexes, using the technologies of X-ray crystallography, structural biology and biochemistry. These works will elucidate the important roles of the proteins in the WSSV assembly or infection, and lay the foundation for in-depth understanding the molecular mechanisms of WSSV assembly and drug design based on blocking WSSV infection.

对虾白斑症病毒（WSSV）已成为对虾养殖产业危害最大的病原之一，该病毒宿主广，毒性强，感染对虾后3到7天内有90%-100%的致死率，每年导致对虾养殖产业数十亿美元的经济损失。遗憾的是迄今对该病毒致病机制了解甚少，目前尚无有效的应对该病毒的防治策略。对WSSV囊膜组装和感染相关关键蛋白的结构和功能的研究，可为深入阐释和理解WSSV组装和感染机制以及基于WSSV组装、感染机制而进行的的抑制剂开发等工作提供重要的理论和实际指导依据。基于以上原因本项目拟采用X-射线晶体学等结构生物学以及生物化学方法研究与WSSV囊膜组装和WSSV感染相关结构蛋白的结构和功能，如WSSV的囊膜蛋白VP19和VP24、核壳体蛋白VP51C以及相关蛋白复合物等，揭示这些蛋白在WSSV囊膜组装或感染中的地位和调控作用，为研究WSSV组装和感染的分子机制和针对于阻断WSSV感染的药物设计奠定基础。

对虾白斑症病毒（WSSV）已成为对虾养殖产业危害最大的病原之一，该病毒宿主广，毒性强，感染对虾后3到7天内有90%-100%的致死率，每年导致对虾养殖产业数十亿美元的经济损失。遗憾的是迄今对该病毒的致病机制了解甚少，目前尚无有效的应对该病毒的防治策略。对WSSV囊膜组装和感染相关蛋白的结构和功能的研究，可为深入阐释和理解WSSV组装和感染机制以及基于WSSV组装、感染机制而进行的抑制剂开发等工作提供重要的理论和实际指导依据。基于以上原因本项目运用了X-射线晶体学方法解析了在WSSV囊膜组装中起核心蛋白作用的囊膜蛋白VP24的结构，重新定位了VP24在囊膜的位置，即VP24位于囊膜外侧，它可以与宿主的几丁质结合，锚定宿主便宜VP28黏附到宿主细胞，从而引发感染，这为深入研究WSSV的囊膜组装和感染机制及抑制剂开发提供了理论依据。此外，也对其他囊膜组装或感染相关蛋白在原核表达系统的进行了表达，分离纯化及结晶实验初筛，为后续的结构生物学研究奠定基础。