Zhu Li, Zhao Wenming, Lu Jiao, Li Shan, Zhou Kai, Jiang Wei, Duan Xuefeng, Fu Lifeng, Yu Bolan, Cai Kathy Q, Gao George Fu, Liu Wenjun, Fang Min
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Cell Microbiol. 2019 Aug;21(8):e13038. doi: 10.1111/cmi.13038. Epub 2019 May 16.
Influenza virus matrix 1 protein (M1) is highly conserved and plays essential roles at many stages of virus life cycle. Here, we used a yeast two-hybrid system to identify the host protein SLD5, a component of the GINS complex, which is essential for the initiation of DNA replication in eukaryotic cells, as a new M1 interacting protein. M1 from several different influenza virus strains all interacted with SLD5. Overexpression of SLD5 suppressed influenza virus replication. Transient, stable, or inducible expression of M1 induced host cell cycle blockade at G0/G1 phase. Moreover, SLD5 partially rescued M1 expression- or influenza virus infection-induced G0/G1 phase accumulation in cell lines and primary mouse embryonic fibroblasts. Importantly, SLD5 transgenic mice exhibited higher resistance and improved lung epithelial regeneration after virus infection compared with wild-type mice. Therefore, influenza virus M1 blocks host cell cycle process by interacting with SLD5. Our finding reveals the multifunctional nature of M1 and provides new insight for understanding influenza virus-host interaction.
流感病毒基质1蛋白（M1）高度保守，在病毒生命周期的许多阶段发挥着重要作用。在此，我们利用酵母双杂交系统鉴定出宿主蛋白SLD5，它是GINS复合物的一个组成部分，对真核细胞中DNA复制的起始至关重要，是一种新的与M1相互作用的蛋白。来自几种不同流感病毒株的M1均与SLD5相互作用。SLD5的过表达抑制了流感病毒的复制。M1的瞬时、稳定或诱导表达诱导宿主细胞周期在G0/G1期阻滞。此外，SLD5部分挽救了M1表达或流感病毒感染诱导的细胞系和原代小鼠胚胎成纤维细胞中的G0/G1期积累。重要的是，与野生型小鼠相比，SLD5转基因小鼠在病毒感染后表现出更高的抵抗力和更好的肺上皮再生能力。因此，流感病毒M1通过与SLD5相互作用来阻断宿主细胞周期进程。我们的发现揭示了M1的多功能性质，并为理解流感病毒与宿主的相互作用提供了新的见解。
