流感病毒不断进化变异，对动物和人类健康构成持续威胁，随时可能引发新的动物疫情暴发和公共卫生危机。流感病毒的生活周期实际上是病毒与宿主相互作用的一个过程。因此，研究与流感病毒蛋白相互作用的宿主蛋白，不仅可以深化对流感病毒复制周期调控机制的认知，而且可以为抗流感药物的研发提供潜在的靶标。流感病毒NP蛋白在病毒RNA合成、复制复合体运输和子代病毒包装等过程中发挥关键作用。本项目将以病毒NP蛋白作为研究对象，在前期建立的酵母双杂交系统的基础上，运用酵母双杂交和免疫共沉淀结合质谱鉴定方法，筛选和研究与NP蛋白存在直接相互作用的宿主蛋白，揭示宿主蛋白影响流感病毒复制及生物学特性的潜在机制。本项目的实施将进一步完善流感病毒蛋白与宿主蛋白形成的相互作用网络，加深对流感病毒如何完成其复制周期的理解，为研制新型抗流感病毒药物以及干预治疗提供科学依据。

Influenza viruses continue to evolve and challenge the health of both animals and humans, which may cause new outbreak in animals and public health crisis at any time. The life cycle of influenza virus is actually a process composed of virus-host interactions. Therefore, the study on the host interacting partners of the influenza viral proteins can not only deepen the perception on the regulating mechanisms of influenza virus replication cycle, but also can provide potential targets for antiviral drug research and development. Influenza virus NP protein plays important roles in the virus life cycle, such as synthesis of viral RNAs, trafficking of viral ribonucleoprotein (vRNP) complexes and assembly of progeny viruses. We have previously successfully established a yeast two hybrid system (Y2H) to screen for potential binding partners with influenza viral proteins. In this project, we will further combine the Y2H system with the co-immunoprecipitation and mass spectrometry approach to comprehensively screen for host proteins that interact with the NP protein, and elucidate the potential mechanisms that host proteins affect the replication and biological properties of influenza viruses. The implementation of this project will further improve the interacting networks formed by proteins of both the influenza virus and the host, deepen the understanding on how influenza virus complete its life cycle, and provide scientific basis for the development of new anti-influenza drugs and interventions.