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

Yizhong Wang,Xu Wang,Jieliang Li,Kui Li,Ting Zhang,Wenzhe Ho,Juliet C Peña

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.

Highlights

Green tea has been considered to have a number of physiological and pharmacological health benefits. (− )-Epigallocatechin-3-gallate (EGCG) is the most abundant and bioactive catechin in green tea, which displays strong preventive effects against viral infection, cardiovascular disease, metabolic syndrome, neurodegenerative diseases and cancer[8,9]
Our results revealed that EGCG significantly increases hepatitis C virus (HCV) dsRNAs-induced IFN-λ 1, Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I), and antiviral IFN-stimulated genes (ISGs) expression in both HCV JFH-1-infected and uninfected Huh[7] cells
We demonstrated that EGCG had the ability to enhance HCV dsRNAs-induced innate immune responses in hepatocytes

Summary

Results

Treatment with both EGCG and HCV dsRNAs inhibits HCV. We treated cells with EGCG for 1 h prior to HCV dsRNAs stimulation, we showed that the EGCG treatment can significantly enhance the HCV dsRNAs-induced IFN-λ 1 expression in JFH-1-infected Huh[7] cells, at both mRNA (Fig. 6A,B) and protein levels (Fig. 6C,D), and this effect was dose-dependent. EGCG alone had little effect on the expression of ISG15 (Fig. 7A) and MxA (Fig. 7B), EGCG treatment of HCV-infected cells significantly enhanced the HCV dsRNAs-induced ISG15 and MxA expression at both mRNA and protein levels in a dose-dependent manner (Fig. 7C–G and Fig. S4).

Discussion

Author Contributions

Additional Information