Investigating the role of GTPase in inhibiting HBV replication and enhancing interferon therapy efficacy in chronic hepatitis B patients

Abstract

BackgroundInterferon-alpha (IFNα) is a common treatment for chronic hepatitis B virus (HBV) infection, but its efficacy varies widely among patients. GTPASE, an interferon-stimulated gene (ISG), has recently been identified as a factor in antiviral immunity, though its role in HBV infection is not fully understood. ObjectiveThis study investigates the role of GTPASE in enhancing the antiviral effects of IFNα against HBV and elucidates its mechanism of action. MethodsWe analyzed the impact of GTPASE overexpression and silencing on HBV replication and clearance in HBV-infected cells. Molecular docking studies assessed the interaction between GTPASE and HBV surface antigens (HBs). Clinical samples from HBV patients undergoing Peg-IFNα treatment were also evaluated for GTPASE expression and its correlation with treatment efficacy. ResultsOverexpression of GTPASE led to significant inhibition of HBV replication, increased HBeAg seroconversion, and enhanced HBsAg clearance. GTPASE directly bound to HBs proteins, reducing their levels and affecting viral particle formation. Silencing GTPASE reduced these effects, while combined treatment with Peg-IFNα and GTPASE overexpression further improved antiviral outcomes. Mutational analysis revealed that specific sites in GTPASE are crucial for its antiviral activity. ConclusionsGTPASE acts as a positive regulator in IFNα-induced antiviral immunity against HBV. It enhances the therapeutic efficacy of IFNα by targeting HBs and modulating viral replication. GTPASE levels may serve as a predictive biomarker for response to Peg-IFNα therapy, highlighting its potential for improving individualized treatment strategies for chronic HBV infection.