宿主因子Rab28调控流感病毒复制机制研究

Influenza virus, one of the major causative agents of zoonotic infectious disease, has posted severe threat for the public health. The use of anti-influenza drugs is an important measure to prevent and control influenza infection. However, influenza virus is prone to mutate during circulation, resulting in the emergence of drug-resistant strains. Therefore, the development of novel anti-influenza drugs appears to be very important. Influenza virus relies on host proteins and cellular machinery to complete its infection cycle. The identification of host factors involved in influenza virus infection will advance our understanding of the molecular mechanisms underlying the viral replication cycle and provide potential new targets for the development of anti-influenza drugs. In previous study, we identified a host factor Rab28 by the genome-wide RNAi screening. Preliminary study showed that Rab28 positively regulate the replication of influenza virus. On the basis of these results, we will further investigate the molecular mechanisms of Rab28 in regulating the virus replication. The implementation of the project will provide potential targets for the development of new anti-influenza virus drugs.

流感病毒是重要的人畜共患传染病病原之一，对人类公共卫生安全构成严重的威胁。抗病毒药物是防治流感的重要措施。但是流感病毒变异频繁，在流行过程中易于产生耐药毒株。因此，研制新型抗流感病毒药物显得尤为重要。流感病毒的复制依赖于细胞内大量的宿主因子。通过寻找病毒感染过程中所依赖的关键宿主因子可以加深我们对流感病毒复制周期的认识，为研究抗流感病毒药物提供潜在的新靶点。本实验室利用基因组RNA干扰筛选技术，获得一个宿主因子Rab28，并初步确认了Rab28蛋白对病毒复制发挥正调控作用。因此拟通过本项目的实施，进一步揭示宿主因子Rab28蛋白影响流感病毒复制的分子机制，为研制新型抗流感病毒药物提供潜在的新靶点。

流感病毒是重要的人畜共患传染病病原之一，由于其基因组编码蛋白有限，因此在病毒感染过程中需要借助大量宿主因子的参与。在本项目研究过程中，我们利用基因组RNA干扰技术筛选到宿主因子Rab28，系统研究表明Rab28与流感病毒的NP蛋白存在相互作用。通过RNAi干扰发现Rab28蛋白表达可正调控流感病毒的复制。通过siRNA干扰后检测流感病毒RNA表达水平，发现Rab28下调感染病毒8h后vRNA水平显著低于对照组，表明Rab28可能是在病毒感染的中后期发挥作用，可能抑制流感病毒NP/vRNP的出核过程。通过本项目的实施，进一步深化我们对于宿主因子Rab28通过与NP蛋白互作调控流感病毒复制周期的认识。