title: (-)-Epigallocatechin-3-Gallate Enhances Hepatitis C Virus Double-Stranded RNA Intermediates-Triggered Innate Immune Responses in Hepatocytes.
abstract: (-)-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.
authors.affiliation: Department of Infectious Diseases, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.
authors.forename: Yizhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Jieliang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Juliet C
authors.initials: JC
authors.lastname: Peña
authors.affiliation: Deparment of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Kui
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000378:metabolism; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D016174:Hepacivirus / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007372:Interferons; D007378:Interleukins / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000187:drug effects / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000187:drug effects; D051196:Toll-Like Receptor 3; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D002392:Catechin; D000071457:DEAD Box Protein 58; D007372:Interferons; D007378:Interleukins; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C495344:TLR3 protein, human; C045651:epigallocatechin gallate; C452820:RIGI protein, human