宿主因子DnaJC7调节甲型流感病毒复制机制研究

Influenza virus is an important human pathogen that causes respiratory disease. Influenza A virus not only causes seasonal epidemics, but also causes world pandemics which poses great threat to public health worldwide. It has been confirmed that viral RNA polymerase complex is a crucial determinant of host range specificity and viral pathogenicity. Understanding the mechanisms of viral replication and the interaction between host and RNP are of considerable importance for developing more effective vaccines and antiviral reagents. We found a new host factor DnaJC7, which is associated with PB1 specifically, through affinity-purification screening. Our preliminary results have shown that DnaJC7 could positively regulated influenza A virus replication. We also found that it could affect the localization of vRNP in cells. Therefore, with our expertises in studying the interacting between host factor and viral RNPs, we will elucidate the role of DnaJC7/Hsp40 during influenza virus replication. The result of this study will broad our knowledge on the members of Hsp40 family in regulating influenza virus replication. Meanwhile it may facilitate the development of new antiviral drugs.

流感病毒是一种能够引起人类呼吸道疾病的的重要病原体。它不仅能引起每年的季节性流感大流行，并且能引发高的发病率和死亡率，威胁人类的公共健康。流感病毒的RNP是决定病毒致病能力及宿主范围的因素之一，更好地理解流感病毒复制机制及宿主与病毒RNP的关系将对疫苗的研制以及抗流感药物的研发都起到十分重要的作用。我们通过亲和纯化技术筛选到一个能够与流感病毒聚合酶PB1亚基相互作用的宿主因子DnaJC7。前期的实验发现该因子能够正向调控流感病毒病毒的复制，并能影响vRNP在细胞内的定位。因此本项目将利用本实验室研究宿主因子的成熟平台，通过病毒学及分子生物学的方法，进一步探寻DnaJC7/Hsp40调节流感病毒复制机制，研究结果会进一步完善Hsp40家族蛋白在流感病毒生命周期中的影响及作用机制，同时为抗流感药物的研发提供新的线索。