Yang Yalong, Wang Caiwei, Sun Wenyue, Fu Yue, Wu Xuedong, Zhao Chunyuan, Song Hui, Zhao Wei, Qin Ying
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.
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.
Redox Biol. 2025 Mar;80:103492. doi: 10.1016/j.redox.2025.103492. Epub 2025 Jan 7.
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.
细胞微环境对先天免疫反应的激活起着关键的调控作用。N-氯代牛磺酸（Tau-Cl）是一种内源性代谢产物，在病原体入侵时会大量产生并分泌。然而，其对抗病毒先天免疫反应的影响仍不清楚。在此，我们证明病毒感染会上调细胞内Tau-Cl水平。Tau-Cl可减弱病毒感染诱导的I型干扰素表达，并在体外和体内促进病毒复制。机制上，Tau-Cl促进关键转录因子IRF3在半胱氨酸222和半胱氨酸371位点的氧化，IRF3负责调控I型干扰素的转录。Tau-Cl抑制IRF3的磷酸化和核转位，并阻止IRF3与IFN-β启动子区域结合。因此，我们确定Tau-Cl是IRF3驱动的抗病毒先天反应的内源性抑制剂，并揭示了病毒通过影响宿主微环境的免疫逃逸机制。
