宿主因子DNAJA1参与甲型流感病毒复制机制的研究

项目名称： 宿主因子DNAJA1参与甲型流感病毒复制机制的研究

项目编号： No.31471329

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 邓涛

作者单位： 中国医学科学院病原生物学研究所

项目金额： 80万元

中文摘要： 与其它大部分RNA病毒相比，甲型流感病毒在细胞核中进行病毒RNA转录与复制的过程，使其更依赖病毒与宿主因子相互作用，而且此过程是决定病毒毒力和宿主特异性关键环节之一。本实验室通过前期质谱分析和siRNA筛查，发现宿主因子DNAJA1可能参与了甲型流感病毒的复制，且尚未见报道。我们前期结果表明DNAJA1可正向调控流感病毒在细胞中的复制，而且可在流感病毒RNP小型复制子系统中促进病毒RNA的合成，因此本项目将利用本课题组长期从事流感病毒RNA聚合酶研究的经验和技术平台，从宿主因子可能参与流感病毒RNA合成的多个方面，包括vRNP的装配，vRNP的细胞内转运，以及聚合酶活性等方面进行研究，以阐明DNAJA1调控甲型流感病毒在细胞中的复制的作用机制，并进行各项体内功能验证。该项目的实施有助于我们加深对宿主因子在流感病毒复制的认识，并会为开发新型抗病毒药物提供新思路。

中文关键词： 流感病毒；宿主因子；DNAJA1；核糖核蛋白体

英文摘要： The unusual feature of viral RNA transcription and replication occurring in the nucleus for influenza A virus relies on virus host interaction to a greater extend than other RNA viruses.Moreover,this process is critical in determining virus pathogenicity and virus host-specificity.Through pulldown plus mass spec analysis and siRNA screening, our laboratory newly identified DNAJA1 as a host factor that may regulate influenza A virus replication, which has not been reported before. Our preliminary results have shown that DNAJA1 could positively regulated influenza A virus replication. We also found that it could stimulate viral RNA synthesis in an RNP mini-replicon system. Therefore, based on our expertises on study of host factors and viral RNA polymerase,this project will focus on studying the role of DNAJA1 in all possible aspects invovled in viral RNA synthesis, including vRNP assembly, vRNP transport and RNA polymerase activites, etc. We will further elucidate the molecular mechanisms of DNAJA1 in regulating viral RNA synthesis and to confirm it in in vivo systems. The study will further our understanding of the molecular interactions between host cell and influenza virus, and could ultimately provide new ideas for the development of antiviral drugs.

英文关键词： Influenza virus;Host factors;DNAJA1;Ribnucleoprotein