LncNSPL facilitates influenza A viral immune escape by restricting TRIM25-mediated K63-linked RIG-I ubiquitination

Jingjing Jiang; Yuyu Li; Zeyu Sun; Lan Gong; Xuehui Li; Fan Shi; Jian Yao; Yuting Meng; Xiaohua Meng; Qiong Zhang; Yuchong Wang; Xiaoling Su; Hongyan Diao

doi:10.1016/j.isci.2022.104607

LncNSPL facilitates influenza A viral immune escape by restricting TRIM25-mediated K63-linked RIG-I ubiquitination

iScience. 2022 Jun 15;25(7):104607. doi: 10.1016/j.isci.2022.104607. eCollection 2022 Jul 15.

Authors

Jingjing Jiang¹, Yuyu Li¹, Zeyu Sun¹, Lan Gong², Xuehui Li¹, Fan Shi¹, Jian Yao¹, Yuting Meng¹, Xiaohua Meng¹, Qiong Zhang¹, Yuchong Wang¹, Xiaoling Su¹, Hongyan Diao¹

Affiliations

¹ State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
² Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.

Abstract

Long noncoding RNAs (lncRNAs) participate in host antiviral responses; however, how viruses exploit host lncRNAs for immune evasion remains largely unexplored. Functional screening of differentially expressed lncRNA profile in patients infected with influenza A virus (IAV) revealed that lncNSPL (Gene Symbol: LOC105370355) was highly expressed in monocytes. Deregulated lncNSPL expression in infected monocytes significantly increased type I interferon (IFN-I) production and inhibited IAV replication. Moreover, lncNSPL overexpression in mice increased the susceptibility to IAV infection and impaired IFN-I production. LncNSPL directly bound to retinoic acid-inducible gene I (RIG-I) and blocked the interaction between RIG-I and E3 ligase tripartite interaction motif 25 (TRIM25), reducing TRIM25-mediated lysine 63 (K63)-linked RIG-I ubiquitination and limiting the downstream production of antiviral mediators during the late stage of IAV infection. Our findings provide mechanistic insights into the means by which lncNSPL promotes IAV replication and immune escape via restricting the TRIM25-mediated RIG-I K63-linked ubiquitination. Thus, lncNSPL may represent a promising pharmaceutical target for anti-IAV therapy.

Keywords: Biochemistry; Immunology; Virology.