Endogenous metabolite N-chlorotaurine attenuates antiviral responses by facilitating IRF3 oxidation

Yalong Yang; Caiwei Wang; Wenyue Sun; Yue Fu; Xuedong Wu; Chunyuan Zhao; Hui Song; Wei Zhao; Ying Qin

doi:10.1016/j.redox.2025.103492

Endogenous metabolite N-chlorotaurine attenuates antiviral responses by facilitating IRF3 oxidation

Redox Biol. 2025 Jan 7:80:103492. doi: 10.1016/j.redox.2025.103492. Online ahead of print.

Authors

Yalong Yang¹, Caiwei Wang¹, Wenyue Sun¹, Yue Fu¹, Xuedong Wu¹, Chunyuan Zhao¹, Hui Song¹, Wei Zhao¹, Ying Qin²

Affiliations

¹ Department of Pathogenic Biology, Key Laboratory of Infection and Immunity of Shandong Province, and Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
² Department of Pathogenic Biology, Key Laboratory of Infection and Immunity of Shandong Province, and Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. Electronic address: yingqin@sdu.edu.cn.

PMID: 39799640
DOI: 10.1016/j.redox.2025.103492

Abstract

Cellular microenvironments critically control the activation of innate immune responses. N-chlorotaurine (Tau-Cl) is an endogenous metabolite that is markedly produced and secreted during pathogenic invasion. However, its effect on the antiviral innate immune responses remains unclear. Here, we demonstrate that viral infection upregulates cellular Tau-Cl level. Tau-Cl attenuates viral infection-induced expression of type I IFNs and facilitates viral replication both in vitro and in vivo. Mechanistically, Tau-Cl facilitates the oxidation of IRF3 at Cys222 and Cys371, a key transcription factor that governs the transcription of type I IFNs. Tau-Cl inhibits phosphorylation and nuclear translocation of IRF3, and blocks IRF3 binding to the IFN-β promoter region. Therefore, we identify Tau-Cl as an endogenous suppressor of IRF3-driven antiviral innate responses and uncover an immune escape mechanism of viruses by affecting host microenvironments.

Keywords: Antiviral innate responses; IRF3; N-chlorotaurine (Tau-Cl); Oxidation; Post translational modifications.