Negative Regulation of RIG-I by Tim-3 Promotes H1N1 Infection. (2nd January 2023)

• Record Type: Journal Article
• Authors: Shi, Qingzhu; Li, Ge; Dou, Shuaijie; Tang, Lili; Hou, Chunmei; Wang, Zhiding; Gao, Yang; Gao, Zhenfang; Hao, Ying; Mo, Rongliang; Shen, Beifen; Wang, Renxi; Li, Yuxiang; Han, Gencheng
• Is Part Of: Immunological investigations. Volume 52:Number 1(2023)
• Page Start: 1
• Page End: 19
• Publication Date: 2023-01-02
• Subjects: H1N1 -- macrophage -- RIG-I -- Tim-3; Immunology -- Periodicals; Immunochemistry -- Periodicals; Cellular immunity -- Periodicals; Communicable diseases -- Periodicals; 616.079
• DOI: 10.1080/08820139.2022.2113407
• Languages: English
• ISSNs: 0882-0139

Abstract

ABSTRACT: The mechanisms by which retinoic acid-inducible gene I (RIG-I), a critical RNA virus sensor, is regulated in many biological and pathological processes remain to be determined. Here, we demonstrate that T cell immunoglobulin and mucin protein-3 (Tim-3), an immune checkpoint inhibitor, mediates infection tolerance by suppressing RIG-I-type I interferon pathway. Overexpression or blockade of Tim-3 affects type I interferon expression, virus replication, and tissue damage in mice following H1N1 infection. Tim-3 signaling decreases RIG-I transcription via STAT1 in macrophages and promotes the proteasomal dependent degradation of RIG-I by enhancing K-48-linked ubiquitination via the E3 ligase RNF-122. Silencing RIG-I reversed Tim-3 blockage-mediated upregulation of type I interferon in macrophages. We thus identified a new mechanism through which Tim-3 mediates the immune evasion of H1N1, which may have clinical implications for the treatment of viral diseases.