IFN-α2b通过阻断肝脏中HBx / MSL2 / cccc / HBV / HBx的正反馈回路抑

StephenW

Biochem Biophys Res Commun

. 2020 Jun 18;527(1):76-82.
doi: 10.1016/j.bbrc.2020.04.057. Epub 2020 Apr 25.
IFN-α2b Inhibits the Ethanol enriched-HBV cccDNA Through Blocking a Positive Feedback Loop of HBx/MSL2/cccDNA/HBV/HBx in Liver
Zixian Liu  1 , Jiapei Wang  1 , Hongfeng Yuan  1 , Lei Liu  1 , Yanan Bu  1 , Man Zhao  1 , Guang Yang  1 , Jinyan Feng  1 , Yunxia Liu  1 , Jiangning Li  1 , Qiujia He  1 , Xiaodong Zhang  2
Affiliations
Affiliations

    1
    Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China.
    2
    Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China. Electronic address: [email protected].

    PMID: 32446394 DOI: 10.1016/j.bbrc.2020.04.057

Abstract

Hepatitis B virus (HBV) is a major risk factor for liver diseases, in which HBV covalently closed circular DNA (cccDNA), as the genomic form that templates viral transcription, plays crucial roles in sustaining viral persistence. Clinically, the excessive ethanol intake accelerates the progression of liver diseases with HBV infection. Here, we supposed that ethanol might trigger HBV cccDNA in the liver. Interestingly, we observed that the ethanol remarkably elevated the levels of HBeAg, HBsAg, HBV DNA and cccDNA in HBV-expressing hepatoma cells. Mechanically, the ethanol increased the levels of HBx and MSL2 in vivo and in HBV-expressing HepG2 cells, but not in HBV-free HepG2 cells. Moreover, the down-regulation of MSL2 by small interference RNA could block the ethanol-promoted HBV cccDNA in HepG2.2.15 cells. As a commonly administered treatment for HBV, the effect of IFNα on ethanol-triggered HBV cccDNA remains poorly understood. Strikingly, we showed that the treatment with IFN-α2b inhibited the ethanol-promoted cccDNA through depressing MSL2 in the cells. Thus, we conclude that IFN-α2b inhibits the ethanol-enriched HBV cccDNA through blocking a positive feedback loop of HBx/MSL2/cccDNA/HBV/HBx. Our finding provides new insights into the mechanism by which IFN-α2b inhibits ethanol-enhanced HBV cccDNA. Therapeutically, IFNα may contribute to the cccDNA induced by ethanol in liver.

Keywords: Ethanol; HBx; Hepatitis B virus; IFNα; MSL2; cccDNA.

Copyright © 2020 Elsevier Inc. All rights reserved.

StephenW

生化生物物理学会

。 2020年6月18日; 527（1）：76-82。
doi：10.1016 / j.bbrc.2020.04.057。 Epub 2020年4月25日。
IFN-α2b通过阻断肝脏中HBx / MSL2 / cccc / HBV / HBx的正反馈回路抑制乙醇富集的HBV cccDNA
刘子贤1，王家培1，洪峰源1，刘磊1，延安部1，满昭1，广阳1，金燕峰1，云霞刘1，江宁李1，邱家河1，张晓东2
隶属关系
隶属关系

1个
南开大学生命科学学院肿瘤研究系，天津300071
2
南开大学生命科学学院肿瘤研究系，天津300071电子地址：[email protected]。

PMID：32446394 DOI：10.1016 / j.bbrc.2020.04.057

抽象

乙型肝炎病毒（HBV）是肝脏疾病的主要危险因素，其中乙型肝炎病毒以共价形式封闭环状DNA（cccDNA），作为模板化病毒转录的基因组形式，在维持病毒持久性中起着至关重要的作用。临床上，过量摄入乙醇会加速HBV​​感染引起的肝脏疾病的进展。在这里，我们认为乙醇可能会触发肝脏中的HBV cccDNA。有趣的是，我们观察到乙醇显着提高了表达HBV的肝癌细胞中HBeAg，HBsAg，HBV DNA和cccDNA的水平。从机械上讲，乙醇会增加体内和表达HBV的HepG2细胞中HBx和MSL2的水平，但不会增加无HBV的HepG2细胞中的水平。此外，小干扰RNA对MSL2的下调可能会阻断乙醇促进的HepG2.2.15细胞中的HBV cccDNA。作为常用的HBV疗法，对IFNα对乙醇触发的HBV cccDNA的作用仍知之甚少。令人惊讶的是，我们表明用IFN-α2b处理可通过抑制细胞中的MSL2抑制乙醇促进的cccDNA。因此，我们得出的结论是，IFN-α2b通过阻断HBx / MSL2 / cccDNA / HBV / HBx的正反馈回路来抑制富含乙醇的HBV cccDNA。我们的发现为IFN-α2b抑制乙醇增强的HBV cccDNA的机制提供了新的见解。在治疗上，IFNα可能有助于肝脏中乙醇诱导的cccDNA。

关键字：乙醇； HBx;乙型肝炎病毒; IFNα; MSL2； cccDNA。

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