Mutations at site 207 of influenza a virus NS1 protein switch its function in regulating RIG-I-like receptors mediated antiviral responses
文献类型: 外文期刊
第一作者: Wang, Xingbo
作者: Wang, Xingbo;Lin, Lulu;Si, Wei;Yan, Yan;Dong, Weiren;Jin, Yulan;Zhou, Jiyong;Chen, Zhen;Si, Wei;Huang, Yu;Zhou, Jiyong;Zhou, Jiyong
作者机构:
关键词: IFI35; RIG -I -like receptors; Influenza a virus; NS1; RNA recognition; K48-linked ubiquitination
期刊名称:ANTIVIRAL RESEARCH ( 影响因子:7.6; 五年影响因子:5.8 )
ISSN: 0166-3542
年卷期: 2023 年 215 卷
页码:
收录情况: SCI
摘要: RIG-I-like receptors (RLRs), retinoic acid inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), are pattern recognition receptors through which cells initially sense pathogenic RNA and trigger interferon (IFN) signaling. Herein, we report that interferon induced protein 35 (IFI35) activates the ring finger protein 125 (RNF125)-UbcH5c-dependent degradation of RLRs and represses the recognition by RIG-I and MDA5 of viral RNA to inhibit innate immunity. Furthermore, IFI35 binds selectively to different subtypes of influenza A virus (IAV) nonstructural protein 1 (NS1) with asparagine residue207 (N207). Functionally, the NS1 (N207)-IFI35 interaction restores the activity of RLRs, and IAV with NS1(non-N207) showed high pathogenicity in mice. Big data analysis showed that the 21st century pandemic IAV are almost all characterized by NS1 protein with non-N207. Collectively, our data uncovered the mechanism of IFI35 restricting the activation of RLRs and provides a new drug target comprising the NS1 protein of different IAV subtypes.
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