甲型鸭肝炎病毒2A蛋白在病毒复制和翻译过程中的作用机制研究

甲型鸭肝炎病毒（DHAV）是小RNA病毒家族的一名新成员，其2A蛋白的编码序列与其它已知小RNA病毒相比，表现出显著差异性，不仅其序列是最长的，其潜在的裂解蛋白也最多。我们的初步研究结果表明，鸭肝炎病毒的2A1蛋白在哺乳动物细胞中同样具有自裂解功能。 目前，关于2A蛋白及其裂解产物在鸭肝炎病毒的复制和翻译中的具体功能还不清楚。鉴于此，我们拟在前期研究基础上，利用反向遗传操作平台，运用基因缺失、替换和分子间相互作用(蛋白-蛋白，蛋白-RNA)等技术，系统研究鸭肝炎病毒2A蛋白在病毒基因组的复制、转录和蛋白表达等过程中发挥的作用。该研究将为深入研究DHAV的复制、表达及其调控机制等提供有价值的参考信息。

Duck hepatitis A virus (DHAV) is a new determined member of picornarvirus. By compared and analysed the 2A proteins of DHAV to other viruses,we have found that it has the complex structure as it retains longest coding regeion and up to three potential maturing proteins.In our previous study,we proved that the 2A1 protein of DHAV could self-cleavged in mammalian cells. So far ,the precise role about 2A protein in the process of replication and translation of duck hepatitis virus has not been cleared. In order to obtain an insight into the real role of 2A protein playing in DHAV replication and translation,we plan to construct a series of DHAV replicon mutants, which were deleted or exchanged 2A protein, on the base of the reverse genetic system of DHAV. The precise role of 2A protein in the replication and translation of DHAV will be evaluted by detecting the expression level of the report gene. Besides, we will determine some key sites which are crucial to the function of 2A protein through investigating the interaction between 2A and cellar translation initiation factors or DHAV genomic RNA. These results will provide some important clues for further exploring the regulation mechanisms of replication and translation of DHAV.