(-)-Epigallocatechin-3-gallate enhances poly I:C-induced interferon-λ1 production and inhibits hepatitis C virus replication in hepatocytes

Abstract

AIMTo investigate the effect of (-)-epigallocatechin-3-gallate (EGCG) on polyinosinic-polycytidylic acid (poly I:C)-triggered intracellular innate immunity against hepatitis C virus (HCV) in hepatocytes.METHODSA cell culture model of HCV infection was generated by infecting a hepatoma cell line, Huh7, with HCV JFH-1 strain (JFH-1-Huh7). Poly I:C with a high molecular weight and EGCG were used to stimulate the JFH-1-Huh7 cells. Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of intracellular mRNAs and of intracellular and extracellular HCV RNA. Enzyme-linked immunosorbent assay was used to evaluate the interferon (IFN)-λ1 protein level in the cell culture supernatant. Immunostaining was used to examine HCV core protein expression in Huh7 cells.RESULTSOur recent study showed that HCV replication could impair poly I:C-triggered intracellular innate immune responses in hepatocytes. In the current study, we showed that EGCG treatment significantly increased the poly I:C-induced expression of Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I, and IFN-λ1 in JFH-1-Huh7 cells. In addition, supplementation with EGCG increased the poly I:C-mediated antiviral activity in JFH-1-Huh7 cells at the intracellular and extracellular HCV RNA and protein levels. Further investigation of the mechanisms showed that EGCG treatment significantly enhanced the poly I:C-induced expression of IFN-regulatory factor 9 and several antiviral IFN-stimulated genes, including ISG15, ISG56, myxovirus resistance A, and 2’-5’-oligoadenylate synthetase 1, which encode the key antiviral elements in the IFN signaling pathway.CONCLUSIONOur observations provide experimental evidence that EGCG has the ability to enhance poly I:C-induced intracellular antiviral innate immunity against HCV replication in hepatocytes.

Complementary and Alternative Medicine for the Treatment of Hepatitis C Virus Infection

“…In-vitro experiment used polyinosinicpolycytidylic acid to induce an immune response in Huh cell line infected with the JFH-1 strain of HCV. Treating these cells with Epigallocatechin-3gallate potentiated this immune response furnishing antiviral cytokine release in the cells by transcriptional up-regulation of interferon genes, confirmed through RT-PCR (Wang et al 2017).…”

(-)-Epigallocatechin-3-gallate induces interferon-λ2 expression to anti-influenza A virus in human bronchial epithelial cells (BEAS-2B) through p38 MAPK signaling pathway

“…In the previous study, the crude phenylethanoid glycosides isolated from Ligustrum purpurascens via inducing endogenous IFN-γ had an anti-viral effect against the IAV (28). In other studies, EGCG inhibited HCV replication by enhancing virus dsRNA or poly I:C-induced IFN-λ1 production (17,18). Consequently, these studies provided us with new ideas.…”

“…Previous studies have revealed that EGCG exhibits affects against viral infection, including against the human immunodeficiency virus (HIV) (12), the herpes simplex virus (HSV) (13), the hepatitis B virus (HBV) (14), the hepatitis C virus (HCV) (15), and the Zika virus (16). It has been shown that EGCG enhances virus dsRNA or poly I:C-induced IFN-λ1 production and inhibits HCV replication (17,18). Although many studies have reported that EGCG has anti-influenzavirus effects (19), whether EGCG can induce IFN-λ expression in airway epithelial cells to suppress the influenza virus and related signaling pathways has not been elucidated at this stage.…”

The potential of epigallocatechin gallate in the chemoprevention and therapy of hepatocellular carcinoma

“…In total, it is estimated that there are about 150 million patients who suffer from HCV infection worldwide ( Luna-Cuadros et al, 2022 ). Studies have shown EGCG significantly enhances antiviral innate immune response in hepatocytes by inducing the expression of toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I), and interferon lambda 1 (IFN-λ1) ( Wang et al, 2016 ; Wang Y. Z. et al, 2017 ).…”