病毒对宿主细胞凋亡的显性负性调控机制

病毒利用自身编码的部分蛋白干预宿主细胞的凋亡从而为自身争取足够的生存空间是保证病毒自身扩繁和包装的策略之一。囊泡病毒作为本项目的研究对象，是一类可以编码caspase-like蛋白的昆虫DNA病毒。然而，前人对这类蛋白的功能存在较大争议。由我们已获得的数据来看，这类caspase-like蛋白极有可能是宿主caspase 3/7的显性负性突变体。在此基础之上，本项目将对这种细胞凋亡的显性负性调控机制进行深入且详细的剖析。本项目拟采用质谱技术及免疫共沉淀分析详细的探究caspase-like与其互作蛋白的关系，同时还将借助成熟的杆状病毒研究系统筛选caspase-like的核心功能域和关键功能氨基酸，全面彻底的揭示caspase-like的功能及其对宿主细胞凋亡的调控机制。明确这种细胞凋亡的显性负性调控机制能够为阐明囊泡病毒的致病机制奠定基础，同时为其在其他昆虫病毒病的防治提供新思路。

Encoding several proteins to inhibit the host cellular apoptosis so as to gain sufficient living space for themselves is one of the strategies for the viruses to produce progeny. As the object of this project, ascoviruses are insect viruses with DNA genome that can encode caspase-like protein. However, the function of these viral caspase-like proteins had been controversial according to different scientists. In our previous studies, we proved that the caspase-like protein encoded by ascoviruses are the dominant negative mutant of caspase 3/7: caspase-like do not have any caspase 3/7 activity, but they can interfere the host caspase 3/7 to exhibit their activity. Based on these, this project is aimed to reveal this dominant negative regulation of apoptosis in a profound and detail way. Both mass spectrum and Co-immunocoprecipitation will be used to illustrate the relationship between the caspase-like protein and its interacted proteins, and the Bac-to-Bac system will be used to select the core functional region and the key animo acid of this caspase-like protein. To clarify the mechanism of dominant and negative regulation of apoptosis can lay a foundation for its application in other fields, such as the prevention and control of viral diseases in sericulture and the prevention and control of viral infections in mammals.