Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection

Influenza A virus (IAV) is a leading cause of human respiratory infections and poses a major public health concern. IAV replication can affect the expression of DNA methyltransferases (DNMTs), and the subsequent changes in DNA methylation regulate gene expression and may lead to abnormal gene transcription and translation, yet the underlying mechanisms of virus-induced epigenetic changes from DNA methylation and its role in virus-host interactions remain elusive. Here in this paper, we showed that DNMT1 expression could be suppressed following the inhibition of miR-142-5p or the PI3K/AKT signaling pathway during IAV infection, resulting in demethylation of the promotor region of the 2'-5'-oligoadenylate synthetase-like (OASL) protein and promotion of its expression in A549 cells. OASL expression enhanced RIG-I-mediated interferon induction and then suppressed replication of IAV. Our study elucidated an innate immunity mechanism by which up-regulation of OASL contributes to host antiviral responses via epigenetic modifications in IAV infection, which could provide important insights into the understanding of viral pathogenesis and host antiviral defense.

Automated summary

Influenza A Virus (IAV) is a major public health concern, and its replication can lead to epigenetic changes via DNA methylation, which regulate gene expression. In this study, we found that the suppression of DNMT1 expression during IAV infection results in demethylation of the OASL protein's promoter region, promoting its expression and enhancing host antiviral response. This innate immunity mechanism sheds light on viral pathogenesis and host defense.