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

Abstract

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.

Keywords

• cGAS
• HBx
• IFN-β
• Ubiquitination
• Autophagy