IFI16 induced hepatocyte inflammation with HBV infection by regulating STING-IRF3 pathway

Aims and background: This study explores that in HBV infection, IFI16 further activates IRF3 through the STING pathway, leading to the release of inflammatory factors and thereby causing liver inflammation. This provides new ideas and theoretical basis for the inflammatory damage caused by hepatitis B virus infection, and also offers new therapeutic targets. Methods In vitro experiments were conducted using human hepatoma cell lines (Huh-7 and HepAD38) transfected with HBV DNA. IFI16 was either overexpressed or silenced, and the expression levels of IFI16, STING, IRF3, IFN-β, and IL-29 were evaluated through Western blot and qRT-PCR analyses. In vivo, an HBV-infected BALB/c mouse model was established to further validate the role of the IFI16-STING-IRF3 pathway in HBV-induced hepatic inflammation. Results IFI16 overexpression in HBV-infected Huh-7 and HepAD38 cells increased the expression of STING, IRF3, IFN-β, and IL-29. Conversely, knockdown of IFI16 using siRNA significantly suppressed the expression of these molecules. In vivo studies indicated that IFI16 overexpression elevated serum levels of ALT, AST, HBeAg, and HBsAg, as well as the expression of STING, IRF3, IFN-β, and IL-29. Furthermore, IFI16 expression correlated with the severity of HBV-associated liver fibrosis. Conclusions The IFI16-STING pathway facilitates HBV-induced hepatic inflammation by activating IRF3 and promoting the secretion of pro-inflammatory cytokines, such as IFN-β and IL-29. These insights lay a theoretical groundwork for the development of innovative antiviral therapeutic approaches.