RVFV是一种高致病性蚊传病毒，编码的非结构蛋白NSs是其最关键的毒力因子。NSs在细胞内形成独特的长丝状结构(filament)，这一结构的形成和稳定可能与其介导的毒性效应直接相关，并在中间宿主（传播媒介）和终宿主（哺乳动物）细胞中受不同的机制调控。本项研究拟基于RVFV反向遗传学系统，采用包括分子生物学、蛋白质组学和现代影像学在内的多种技术手段，1)鉴定参与filament形成介导NSs毒性效应的宿主因子；2)阐明关键宿主因子调控NSs毒力的分子机制；3)解析关键宿主因子参与filament形成的动态过程。最终整合上述工作阐明NSs形成filament结构及介导毒性效应的分子机理。这项研究不仅将有助于RVFV致病机制的阐明，也将为针对关键毒力因子NSs的抗病毒药物的研发提供新靶点。

Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus, with non-structural protein NSs as the major virulence factor. NSs forms a unique filamentous structure in infected cells. The formation and stabilization of filament might be directly related to the toxic effect mediated by NSs, which is regulated by different mechanisms in “dead-end” host and arthropod vector cells. In this project, we plan to employ multiple methods including molecular biology, proteomics and modern imaging technologies together with the established reverse genetic system to 1) identify host factors mediating the toxic effect of NSs through participating in the process of filament formation; 2) investigate the mechanism of key host factors in the regulation of NSs virulence; 3) reveal the dynamic process of key host factor participating in the formation of filament. Taken these results together, we will be able to elucidate the mechanism of filament formation and toxic effect mediated by NSs. This work will not only facilitate the comprehensive understanding of the pathogenic mechanism of RVFV, but also provide specific targets for the design and development of novel anti-viral drugs against the RVFV key virulence factor NSs.