HBx inhibits DNA sensing signaling pathway via ubiquitination and autophagy of cGAS

Abstract

BACKGROUND: Cyclic GMP-AMP synthase (cGAS) is a crucial DNA sensor and plays an important role in host antiviral innate immune responses. During hepatitis B virus (HBV) infection, the cGAS signaling pathway can suppress HBV replication. As an important regulatory protein of HBV, hepatitis B virus X protein (HBx) may serve as an antagonistic character to the cGAS/STING signaling pathway. In this study, we aim to investigate the functional role of HBx in the cGAS/STING signaling pathway. METHODS: The effects of HBx on IFN-β promoter activity were measured by Dual-luciferase reporter assays. Ubiquitination and autophagy were analyzed by Western-blot and Co-immunoprecipitation assays. RESULTS: Our results show that HBx down-regulates IFN-I production by directly promoting ubiquitination and autophagy degradation of cGAS. CONCLUSIONS: HBV can antagonize host cGAS DNA sensing to promote HBV replication and provide novel insights to develop novel approaches against HBV infection.