Viral RNA-binding ability conferred by SUMOylation at PB1 K612 of influenza A virus is essential for viral pathogenesis and transmission

文献类型： 外文期刊

第一作者： Li, Junping

作者： Li, Junping;Liang, Libin;Jiang, Li;Wang, Qian;Wen, Xia;Zhao, Yuhui;Cui, Pengfei;Zhang, Yaping;Wang, Guangwen;Li, Qibing;Deng, Guohua;Shi, Jianzhong;Tian, Guobin;Zeng, Xianying;Jiang, Yongping;Liu, Liling;Chen, Hualan;Li, Chengjun

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：6.823； 五年影响因子：7.455 ）

ISSN： 1553-7366

年卷期： 2021 年 17 卷 2 期

页码：

收录情况： SCI

摘要： Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies. Author summary IAV has evolved to exploit the host posttranslational modifications system for its own benefit. The transcription and replication of IAV genome occur in the nucleus of infected cells, which is catalyzed by the RNA-dependent RNA polymerase (RdRp). PB1 is the catalytic subunit and the assembly core of the RdRp. The ability to efficiently bind viral RNA by PB1 is a prerequisite for the RdRp to fulfil its function. In this study, we demonstrated that PB1 protein from different subtypes of IAV is a target of SUMOylation in both transfected and infected cells, and identified K612 of PB1 as the key SUMOylation site. The vRNP complex activity, replication in vitro, pathogenicity in mice and airborne transmission among ferrets were dramatically attenuated when the SUMOylation-defective PB1/K612R mutation was introduced. Notably, we found that SUMOylation at K612 is essential for PB1 to acquire the ability to efficiently bind viral RNA, thus allowing for the RdRp to transcribe and replicate the viral genome. Our findings therefore thoroughly explore the contribution of PB1 SUMOylation on influenza infection and establish SUMOylation site PB1 K612 as a potential target for anti-influenza drug development.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序