Li Yong, Zhu Chuanlong, Wang Faxi, Zhu Tiantian, Li Jun, Liu Shufeng, Xiao Fei
Department and Institute of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Mediators Inflamm. 2016;2016:3894816. doi: 10.1155/2016/3894816. Epub 2016 Dec 18.
Interferon- (IFN-) has limited response rate in the treatment of chronic hepatitis B (CHB). The underlying mechanism of differential responsiveness to IFN remains elusive. It has been recently reported that SART1 mediates antiviral effects of IFN- in the hepatitis C virus (HCV) cell culture model. In this study, we investigated the role of SART1 in antiviral activity of IFN- against hepatitis B virus (HBV) using blood and liver biopsy samples from chronic hepatitis B patients treated with pegylated IFN- and HepG2 cells transfected with cloned HBV DNA. We observed that the basal SART1 expression in liver and PBMCs before IFN treatment was significantly higher in responders than in nonresponders. Furthermore, baseline SART1 expression level positively correlated with the degree of HBV DNA and HBeAg decline after IFN treatment. Mechanistically, silencing SART1 abrogated the antiviral activity of IFN-, reduced the expression of IFN-stimulated genes (ISGs) Mx, OAS, and PKR, and attenuated JAK-STAT signaling in HepG2 cells, suggesting that SART1 regulates IFN-mediated antiviral activity through JAK-STAT signaling and ISG expression. Our study elucidates the important role of SART1 in IFN-mediated anti-HBV response and provides new insights into understanding variation of IFN treatment response in CHB patients.
干扰素-γ（IFN-γ）在慢性乙型肝炎（CHB）治疗中的应答率有限。对IFN应答差异的潜在机制仍不清楚。最近有报道称，SART1在丙型肝炎病毒（HCV）细胞培养模型中介导IFN-γ的抗病毒作用。在本研究中，我们使用接受聚乙二醇化IFN-γ治疗的慢性乙型肝炎患者的血液和肝活检样本，以及转染了克隆HBV DNA的HepG2细胞，研究了SART1在IFN-γ抗乙型肝炎病毒（HBV）活性中的作用。我们观察到，IFN治疗前肝脏和外周血单个核细胞（PBMC）中的基础SART1表达在应答者中显著高于无应答者。此外，基线SART1表达水平与IFN治疗后HBV DNA和HBeAg下降程度呈正相关。机制上，沉默SART1可消除IFN-γ的抗病毒活性，降低IFN刺激基因（ISG）Mx、OAS和PKR的表达，并减弱HepG2细胞中的JAK-STAT信号传导，提示SART1通过JAK-STAT信号传导和ISG表达调节IFN介导的抗病毒活性。我们的研究阐明了SART1在IFN介导的抗HBV应答中的重要作用，并为理解CHB患者IFN治疗应答的差异提供了新的见解。
