Epigallocatechin-3-gallate inhibits replication of influenza A virus via restoring the host methylated genes following infection.

Abstract

Influenza is a highly infectious disease caused by several types of viruses, including the influenza A virus (IAV), influenza B virus, and rarely, the influenza C virus. Epigallocatechin gallate (EGCG), a natural compound found in green tea, has shown promising effects in inhibiting viral infections. In this study, we investigated the methylation changes that occur following IAV infection, specifically focusing on the down-regulation of ten-eleven translocation 1 (TET1) and TET2 gene expression at both RNA and protein levels. We found that the methylation process triggered by IAV infection leads to the down-regulation of TET1 and TET2. Importantly, treatment with the methylation inhibitor epigallocatechin-3-gallate (EGCG) can prevent IAV infection by disrupting the DNA methylation changes induced by the virus in A549 cells. Our results demonstrate that EGCG treatment significantly alters DNA methylation patterns in human lung epithelial cells (A549) after IAV infection. The treatment appears to down-regulate the expression of DNA methylation co-factors, such as DNMT1 and methionine synthase (MS), which are significantly reduced following IAV infection at 24 h post-infection. Additionally, EGCG treatment led to a marked increase in the gene expression of TET1 and TET2, enzymes responsible for DNA demethylation. We also observed a significant decrease in the production of pro-inflammatory cytokines, specifically interleukin-6 (IL-6) and interferon beta (IFN-β), in infected A549 cells treated with EGCG compared to untreated or control cells. The concentration of IFN-β was notably lower in the EGCG-treated infected cells, in contrast to control cells where IFN-β levels increased significantly up to 200 pm/mL at 12 h post-infection. Similarly, IL-6 levels were significantly reduced in EGCG-treated cells. Overall, this study provides evidence that EGCG, a methylation inhibitor, can modulate DNA methylation pathways in IAV-infected cells by targeting DNMT1 and MS, leading to the inhibition of IAV replication. These findings suggest that EGCG could be a promising therapeutic agent for preventing or reducing IAV infection.