Negative Regulation of RIG-I by Tim-3 Promotes H1N1 Infection.

Autor:	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
Předmět:	HEPATITIS A virus cellular receptors TYPE I interferons IMMUNE checkpoint inhibitors UBIQUITIN ligases VIRUS diseases
Zdroj:	Immunological Investigations; Jan2023, Vol. 52 Issue 1, p1-19, 19p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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