HBx 通过泛素化和 cGAS 的自噬来抑制 DNA 感应信号通路。
HBx inhibits DNA sensing signaling pathway via ubiquitination and autophagy of cGAS.
机构信息
Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjing Road, Yuzhong District, Chongqing, 400010, China.
Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
出版信息
Virol J. 2022 Mar 28;19(1):55. doi: 10.1186/s12985-022-01785-3.
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.
背景
环鸟苷酸-腺苷酸合酶（cGAS）是一种重要的 DNA 传感器，在宿主抗病毒先天免疫反应中发挥重要作用。在乙型肝炎病毒（HBV）感染过程中，cGAS 信号通路可以抑制 HBV 复制。乙型肝炎病毒 X 蛋白（HBx）作为 HBV 的重要调节蛋白，可能作为 cGAS/STING 信号通路的拮抗物。本研究旨在探讨 HBx 在 cGAS/STING 信号通路中的功能作用。
方法
通过双荧光素酶报告基因检测分析 HBx 对 IFN-β 启动子活性的影响。通过 Western-blot 和 Co-immunoprecipitation 实验分析泛素化和自噬。
结果
我们的结果表明，HBx 通过直接促进 cGAS 的泛素化和自噬降解来下调 IFN-I 的产生。
结论
HBV 可以拮抗宿主的 cGAS DNA 感应，促进 HBV 复制，为开发针对 HBV 感染的新方法提供了新的思路。
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