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Updated: Sep 28, 2025

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
Published on: December 21, 2019
HBx inhibits DNA sensing signaling pathway via ubiquitination and autophagy of cGAS
Hong Chen1, Linshan Jiang1, Shu Chen1
1Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjing Road, Yuzhong District, Chongqing, 400010, China.
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.
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