USP14 promotes K63‐linked RIG‐I deubiquitination and suppresses antiviral immune responses. Issue 1 (28th November 2018)

• Record Type: Journal Article
• Authors: Li, Hongrui; Zhao, Zizhao; Ling, Jing; Pan, Linhui; Zhao, Xibao; Zhu, Huihui; Yu, Juan; Xie, Bin; Shen, Jianzhong; Chen, Weilin
• Is Part Of: European journal of immunology. Volume 49:Issue 1(2019)
• Page Start: 42
• Page End: 53
• Publication Date: 2018-11-28
• Subjects: Deubiquitination -- RIG‐I‐like receptors -- RNA virus sensor -- USP14 -- Vesicular stomatitis virus (VSV); Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201847603
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Retinoic acid‐inducible gene I (RIG‐I) is a critical RNA virus sensor that initiates antiviral immune response through K63‐linked ubiquitination. In this study, we demonstrated USP14, a deubiquitinating enzyme, as a negative regulator in antiviral responses by directly deubiquitinating K63‐linked RIG‐I. USP14 knockdown significantly enhanced RIG‐I‐triggered type I IFN signaling and inhibited vesicular stomatitis virus (VSV) replication both in mouse peritoneal macrophages and THP1 cells. USP14 overexpression in HeLa cells attenuated RIG‐I‐triggered IFN‐β expression and promoted VSV replication. Besides, USP14‐specific inhibitor, IU1, increased RIG‐I‐mediated type I IFN production and antiviral responses in vitro and in vivo. In addition, USP14 could interact with RIG‐I and remove RIG‐I K63‐linked polyubiquitination chains. This article is the first to report that USP14 acts as a negative regulator in antiviral response through deubiquitinating K63‐linked RIG‐I. These findings provide insights into a potential new therapy targeting USP14 for RNA virus‐related diseases. Abstract : Triggered by RNA virus, USP14 acts as a negative regulator through deubiquitinating K63‐linked RIG‐I in innate immune response. These findings provide insights into a potential new therapy targeting USP14 for RNA virus related diseases.