Wang Yizhong, Li Jieliang, Wang Xu, Peña Juliet C, Li Kui, Zhang Ting, Ho Wenzhe
Department of Infectious Diseases, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.
Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Sci Rep. 2016 Feb 16;6:21595. doi: 10.1038/srep21595.
(-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol component of green tea, has recently been identified as an inhibitor of hepatitis C virus (HCV) entry. Here, we examined whether EGCG can enhance hepatocyte-mediated intracellular innate immunity against HCV. HCV dsRNAs (Core, E1-P7, NS-3'NTR and NS5A) induced interferon-λ1 (IFN-λ1) expression in human hepatocytes. These HCV dsRNAs also induced the expression of Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I) and several antiviral IFN-stimulated genes (ISGs) expression. Although EGCG treatment of hepatocytes alone had little effect on TLR3 and RIG-I signaling pathways, EGCG significantly enhanced HCV dsRNAs-induced the expression of IFN-λ1, TLR3, RIG-I and antiviral ISGs in hepatocytes. Furthermore, treatment of HCV-infected hepatocytes with EGCG and HCV dsRNAs inhibited viral replication. Given that EGCG has the ability to enhance HCV dsRNAs-induced intracellular antiviral innate immunity against HCV, suggesting the potential application of EGCG as a new anti-HCV agent for HCV therapy.
（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶的主要多酚成分，最近被确定为丙型肝炎病毒（HCV）进入的抑制剂。在此，我们研究了EGCG是否能增强肝细胞介导的针对HCV的细胞内固有免疫。HCV双链RNA（核心、E1-P7、NS-3'NTR和NS5A）在人肝细胞中诱导干扰素-λ1（IFN-λ1）表达。这些HCV双链RNA还诱导了Toll样受体3（TLR3）、视黄酸诱导基因I（RIG-I）以及几种抗病毒干扰素刺激基因（ISG）的表达。虽然单独用EGCG处理肝细胞对TLR3和RIG-I信号通路影响不大，但EGCG显著增强了HCV双链RNA诱导的肝细胞中IFN-λ1、TLR3、RIG-I和抗病毒ISG的表达。此外，用EGCG和HCV双链RNA处理HCV感染的肝细胞可抑制病毒复制。鉴于EGCG有能力增强HCV双链RNA诱导的针对HCV的细胞内抗病毒固有免疫，提示EGCG作为一种新的抗HCV药物在HCV治疗中的潜在应用。
