干扰素
抄写(语言学)
法尼甾体X受体
化学
转录因子
药理学
细胞生物学
癌症研究
计算生物学
生物
生物化学
病毒学
核受体
哲学
基因
语言学
作者
Liang Xue,Kunpeng Liu,Xin Jia,Cuiqin Cheng,Meiqi Zhang,Ling‐Dong Kong,Qifa Li,Zhe Liu,Min Li,Junliang Li,Yao Wang,Anlong Xu
标识
DOI:10.1016/j.apsb.2024.05.005
摘要
Bile acids (BAs) are natural metabolites in mammals and have the potential to function as drugs against viral infection. However, the limited understanding of chenodeoxycholic acid (CDCA) receptors and downstream signaling, along with its lower suppression efficiency in inhibiting virus infection limits its clinical application. In this study, we demonstrate that farnesoid X receptor (FXR), the receptor of CDCA, negatively regulates interferon signaling, thereby contributing to the reduced effectiveness of CDCA against virus replication. FXR deficiency or pharmacological inhibition enhances interferon signaling activation to suppress virus infection. Mechanistically, FXR impairs the DNA binding and transcriptional abilities of activated interferon regulatory factor 3 (IRF3) through interaction. Reduced IRF3 transcriptional activity by FXR–IRF3 interaction significantly undermines the expression of Interferon Beta 1 (IFNB1) and the antiviral response of cells, especially upon the CDCA treatment. In FXR-deficient cells, or when combined with Z-guggulsterone (GUGG) treatment, CDCA exhibits a more potent ability to restrict virus infection. Thus, these findings suggest that FXR serves as a limiting factor for CDCA in inhibiting virus replication, which can be attributed to the "signaling-brake" roles of FXR in interferon signaling. Targeting FXR inhibition represents a promising pharmaceutical strategy for the clinical application of BAs metabolites as antiviral drugs.
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