(-)-Epigallocatechin-3-Gallate Enhances Hepatitis C Virus Double-Stranded RNA Intermediates-Triggered Innate Immune Responses in Hepatocytes

Sci Rep. 2016 Feb 16:6:21595. doi: 10.1038/srep21595.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / metabolism
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Catechin / metabolism
  • Cell Line, Tumor
  • DEAD Box Protein 58
  • Hepacivirus / metabolism*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Hepatocytes / virology*
  • Humans
  • Immunity, Innate / drug effects*
  • Interferons
  • Interleukins / metabolism
  • RNA, Double-Stranded / drug effects
  • RNA, Double-Stranded / metabolism
  • RNA, Viral / metabolism*
  • Receptors, Immunologic
  • Signal Transduction / drug effects
  • Toll-Like Receptor 3

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interleukins
  • RNA, Double-Stranded
  • RNA, Viral
  • Receptors, Immunologic
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Catechin
  • Interferons
  • epigallocatechin gallate
  • RIGI protein, human
  • DEAD Box Protein 58