沙粒病毒是一类具有囊膜的负链分节RNA病毒，包括拉沙热病毒（LASV）、鸠宁病毒（JUNV）等对人类有重要威胁的烈性病毒，目前无FDA批准的特异性针对沙粒病毒的疫苗或药物，原因之一在于对其复制机制及致病机理不清楚。本项目前期系统研究了LASV等沙粒病毒和宿主的蛋白相互作用，发现病毒膜蛋白GPC和基质蛋白Z与核转运蛋白存在互作；并发现核转运蛋白影响沙粒病毒出芽，但和其出入核功能无关；此外还发现核转运蛋白与克里米亚刚果出血热病毒（CCHFV）、发热伴血小板减少综合征病毒（SFTSV）的膜蛋白也存在互作。在本项目中，我们拟深入研究核转运蛋白影响沙粒病毒出芽的分子机制，探索其是否参与CCHFV、SFTSV等其它烈性病毒的出芽过程。本项目的研究将阐明核转运蛋白参与沙粒病毒及其它烈性病毒复制过程的新的分子机制，这将有利于我们进一步了解这些病毒的复制过程及致病机理，为新药研发提供潜在的新靶标及理论支持。

Arenaviruses are a family of enveloped negative-stranded RNA viruses, including Lassa fever virus (LASV) and Junin virus (JUNV), which pose serious threats to human beings. There are no FDA-approved vaccines or drugs for arenaviruses, and one of the important reasons is that the mechanisms of virus replication and pathogenesis are not clear. Our preliminary protein interaction analysis of arenavirus (including LASV) and host cells indicated that multiple proteins of karyopherin family can interact with GPC and Z of arenavirus. Further functional study indicated that karyopherin can affect the budding process of arenavirus. We also found G proteins of other viruses in Bunyavirales, including Crimean-Congo hemorrhagic fever virus (CCHFV) and severe fever with thrombocytopenia syndrome virus (SFTSV), can also interact with karyopherin. In this project, we will investigate how karyopherin affects arenavirus budding process, and explore whether karyopherin can affect budding of other bunyaviruses that can cause hemorrhagic fever. Through the investigation of this project, we will clarify the mechanism of how karyopherin affects the replication of arenavirus and other bunyaviruses that can cause hemorrhagic fever, and this can help us to better understand the mechanisms of replication and pathogenesis of these viruses, providing potential targets and theoretical support for the development of antiviral drugs.