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

HBx inhibits DNA sensing signaling pathway via ubiquitination and autophagy of cGAS.
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HBx 通过 cGAS 泛素化和自噬抑制 DNA 传感信号通路

DOI:
10.1186/s12985-022-01785-3
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发表时间:
2022-03-28
期刊:
影响因子:
4.8
通讯作者:
Chen W
Chen W
中科院分区:
医学3区
文献类型:
--
作者:
Chen H;Jiang L;Chen S;Hu Q;Huang Y;Wu Y;Chen W

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环GMP-AMP合酶(cGAS)是一种重要的DNA传感器,在宿主抗病毒天然免疫应答中起重要作用。在B型肝炎病毒(HBV)感染期间,cGAS信号通路可抑制HBV复制。作为HBV的重要调控蛋白,B型肝炎病毒X蛋白(HBx)可能对cGAS/STING信号通路具有拮抗作用。在这项研究中,我们的目的是研究HBx在cGAS/STING信号通路中的功能作用。通过双荧光素酶报告基因测定来测量HBx对IFN-β启动子活性的影响。通过Western印迹和免疫共沉淀分析泛素化和自噬。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。HBV可以拮抗宿主cGAS DNA传感以促进HBV复制,并为开发抗HBV感染的新方法提供新的见解。
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. 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. Our results show that HBx down-regulates IFN-I production by directly promoting ubiquitination and autophagy degradation of cGAS. 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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