The lignan compound matairesinol monoglucoside induces type I interferon production in HBV infection immunity by regulating STING signaling.

Background: the urgent need for effective prevention and treatment strategies for hepatitis B virus (HBV) has driven extensive research into natural compounds. This study aims to explore the therapeutic potential of matairesinol monoglucoside (MMG) in the treatment of HBV infection.

Methods: primary hepatocytes and Kupffer cells were isolated from wild-type (WT) or stimulator of interferon genes (STING) knockout mice and subsequently infected with AAV-HBV to establish an in vitro anti-HBV assay model. The anti-HBV effects of MMG were assessed by measuring HBV DNA, HBsAg, and HBeAg levels, as well as using qRT-PCR and ELISA to evaluate type I interferon markers (IFN-α and IFN-β), and a luciferase assay. In vivo anti-HBV effects were determined by pre-treating mice with MMG prior to AAV-HBV infection.

Results: MMG treatment significantly reduced the expression of HBV DNA, HBsAg, and HBeAg in both primary hepatocytes and Kupffer cells. Additionally, MMG enhanced the production of type I interferons (IFN-α and IFN-β) in both cell types. The knockout of STING diminished the effects of MMG on type I interferon production. Mechanistically, MMG was shown to modulate the STING-TBK1-IRF3 signaling axis, leading to increased IFN production.

Conclusions: MMG shows promise as a potential therapeutic agent against HBV by targeting the STING signaling pathway.