鸭甲肝病毒复制相关的主要酶蛋白功能探究

鸭甲肝病毒(DHAV)可引起3周龄以内雏鸭发生急性、高度接触性传染病，发病急，致死率可达90-95%，危害严重。但目前国内外尚无关于DHAV酶蛋白在病毒复制中作用的研究，本研究对DHAV的主要酶蛋白2A、3C和3D在病毒复制中的作用进行研究，包括：①2A的数目、自我剪切功能及机制、影响自我剪切功能的因素、亚细胞定位及与病毒RNA的相互作用、与细胞凋亡的关系；②3C的蛋白水解活性及其影响因素、RNA结合活性、与细胞凋亡的关系；③3D的RdRp酶活性和免疫增强作用；④2C、3C和3D功能在防治中的应用：探究基于2A和3C的抗病毒治疗、利用2A和3C构建空衣壳疫苗及3D的免疫佐剂作用，从而解析2A、3C和3D的功能。研究结果将加深人们对DHAV复制与繁殖过程的认识，为阐明DHAV的致病机制提供科学数据，为防治DHAV新型疫苗和新药研究提供理论指导，具有重要科学价值、理论和实际意义。

Duck hepatitis A virus (DHAV) can cause an acute, highly contagious disease within three weeks ducklings which the mortality rate is 90-95 % and lead to an extremely serious harm in duck industry. However, no any research works involved in the proteases function with the replication process were investigated at domestic and oversea. This research project mainly concentrate on the functional role of 2Apro、3Cpro and 3Dpol in the process of replication, includingⅠ, the number of 2Apro、function and mechanism auto-cleavage and it's affecting factors、sub-cellular localization and the interaction with viral RNA and the relationship with apoptosis;Ⅱ, proteolysis activity of 3Cpro and its influencing factors、binding activity with viral RNA, and the relationship with apoptosis; Ⅲ, RNA dependent RNA polymerase (RdRp) activity and immune enhancement by 3Dpol; Ⅳ, application of prophylaxis and treatment of 2Apro、3Cpro and 3Dpol: exploration of antiviral therapy and an empty capsid vaccine based on 2Aproand 3Cpro, and the immune adjuvant effect by 3Dpol, all those works are vital to elucidate the function of 2Apro、3Cpro and 3Dpol. Those investigations will further the understanding of DHAV replication and proliferation, and then provide scientific data and theoretical guidance for elucidating the pathogenic mechanisms and new vaccine design and drug development of DHAV which has important scientific value, theoretical and practical significance.