CHID1 positively regulates RLR antiviral signaling by targeting the RIG‐I/VISA signalosome

• Published in: Journal of medical virology Vol. 91; no. 9; pp. 1668 - 1678
• Main Authors: Li, Sheng‐Na, Ling, Ting, Yang, Ya‐Xian, Huang, Jing‐Ping, Xu, Liang‐Guo
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2019
• Subjects: Adapters; Adaptor Proteins, Signal Transducing - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell activation; CHID1; Chitinase; Cytokines; Cytoplasm; DEAD Box Protein 58 - metabolism; Gene Expression; Gene Knockdown Techniques; HEK293 Cells; Humans; Inflammation; Interferon; Interferon regulatory factor; Interferon regulatory factor 3; Interferon-beta - biosynthesis; Kinases; Pattern recognition; Pattern recognition receptors; Proteome; Proteomics - methods; Receptors; Receptors, Immunologic; Receptors, Pattern Recognition - metabolism; Retinoic acid; Ribonucleic acid; RIG‐I; RNA; Signal Transduction; Signaling; Tumor necrosis factor receptors; Ubiquitination; Virology; Viruses; VISA; CHID1; RIG-I; VISA; ubiquitination
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.25508

Retinoic acid‐inducible gene‐I (RIG‐I) belongs to the RIGI‐like receptors (RLRs), a class of primary pattern recognition receptors. It senses viral double‐strand RNA in the cytoplasm and delivers the activated signal to its adaptor virus‐induced signaling adapter (VISA), which then recruits the downstream TNF receptor‐associated factors and kinases, triggering a downstream signal cascade that leads to the production of proinflammatory cytokines and antiviral interferons (IFNs). However, the mechanism of RIG‐I‐mediated antiviral signaling is not fully understood. Here, we demonstrate that chitinase domain‐containing 1 (CHID1), a member of the chitinase family, positively regulates the RLR antiviral signaling pathway by targeting the RIG‐I/VISA signalosome. CHID1 overexpression enhances the activation of nuclear factor κB (NF‐кB) and interferon regulatory factor 3 (IRF3) triggered by Sendai virus (SeV) by promoting the polyubiquitination of RIG‐I and VISA, thereby potentiating IFN‐β production. CHID1 knockdown in human 239T cells inhibits SeV‐induced activation of IRF3 and NF‐κB and the induction of IFN‐β. These results indicate that CHID1 positively regulates RLR antiviral signal, revealing the novel mechanism of the RIG‐I antiviral signaling pathway.