Interferon-induced miR-7705 modulates the anti-virus activity of cholesterol 25-hydroxylase.

ABSTRACT: Cholesterol 25-hydroxylase (CH25H), an interferon-stimulated gene (ISG), has been implicated in broad-spectrum antiviral immunity. Here, we identify CH25H as a potent suppressor of hepatitis B virus (HBV) replication that significantly outperforms IFN-α in reducing HBV DNA, pregenomic RNA (pgRNA), HBsAg, and HBeAg, without inducing cytotoxicity. However, CH25H is weakly expressed in hepatocytes and only modestly induced by type I interferon. We found that CH25H expression is tightly controlled by microRNAs, especially miR-7705, which is induced by IFN-α in a STAT1-dependent manner. miR-7705 directly targets the 3'UTR of CH25H, suppressing its expression and enhancing HBV replication. Knockdown of miR-7705 restores CH25H levels, enhances IFN-induced antiviral responses, and suppresses HBV r

SUBMITTER: Wang L 

PROVIDER: S-EPMC12455982 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature