乙型肝炎病毒共价闭合环形DNA稳态独立于慢性HBV感染期间的

StephenW

J Viral Hepat. 2017 Feb 9. doi: 10.1111/jvh.12689. [Epub ahead of print]
Hepatitis B Virus covalently closed circular DNA homeostasis is independent of the lymphotoxin pathway during chronic HBV infection.Meier MA1, Suslov A1, Ketterer S1, Heim MH1,2, Wieland SF1.
Author information

• 1Department of Biomedicine, University Hospital (USB), University of Basel, 4031, Basel, Switzerland.
• 2Division of Gastroenterology and Hepatology, University Hospital (USB), University of Basel, 4031, Basel, Switzerland.
  

AbstractCurrent treatment options for patients with chronic hepatitis B virus (HBV) infection are not curative as they are not effective in eliminating covalently closed circular DNA (cccDNA). cccDNA is a stable template for HBV transcription in the nucleus of hepatocytes and is thought to be one of the main factors responsible for HBV persistence. Recently, activation of the lymphotoxin beta receptor (LTβR) has been shown to trigger degradation of cccDNA through induction of cytidine deaminases of the APOBEC3 family in HBV cell culture model systems. To assess the presence and relevance of such mechanisms in the liver of chronically HBV infected patients, we compared intrahepatic cccDNA levels with the expression levels of lymphotoxins and some of their target genes (e.g. APOBEC deaminases) in liver biopsy tissue. Our results confirm elevated gene expression levels of components of the lymphotoxin pathway including lymphotoxin alpha (LTα), lymphotoxin beta (LTβ), APOBEC3B (A3B) and APOBEC3G (A3G) in the chronically HBV infected liver compared to uninfected liver. Furthermore, expression levels of the genes of the APOBEC deaminase family were correlated with those of LTα and LTβ gene expression, consistent with lymphotoxin-mediated upregulation of APOBEC gene expression. However, intrahepatic cccDNA and HBV replication levels were not correlated with LTα, LTβ and APOBEC gene expression. In conclusion, these results suggest that although the lymphotoxin pathway is activated in the chronically HBV infected liver, it has no major impact on HBV cccDNA metabolism in chronic HBV infection. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS: APOBEC3; Hepatitis B virus; Human liver biopsy; Lymphotoxin; cccDNA degradation

PMID:28182305DOI:10.1111/jvh.12689

StephenW

J病毒Hepat。 2017年2月9日。doi：10.1111 / jvh.12689。 [打印前的电子版]
乙型肝炎病毒共价闭合环形DNA稳态独立于慢性HBV感染期间的淋巴毒素通路。
Meier MA1，Suslov A1，Ketterer S1，Heim MH1,2，Wieland SF1。
作者信息

    1生物医学部，大学医院（USB），巴塞尔大学，4031，瑞士巴塞尔。
    Diivision of Gastroenterology and Hepatology，University Hospital（USB），University of Basel，4031，Basel，Switzerland。

抽象

目前用于慢性乙型肝炎病毒（HBV）感染的患者的治疗选择不是治愈性的，因为它们不能有效消除共价闭合的环状DNA（cccDNA）。 cccDNA是肝细胞核中HBV转录的稳定模板，并且被认为是导致HBV持续存在的主要因素之一。最近，已经显示淋巴毒素β受体（LTβR）的激活通过在HBV细胞培养模型系统中诱导APOBEC3家族的胞苷脱氨酶而引发cccDNA的降解。为了评估这种机制在慢性HBV感染患者的肝脏中的存在和相关性，我们比较肝内cccDNA水平与淋巴毒素和一些他们的目标基因（例如APOBEC脱氨酶）在肝活检组织中的表达水平。我们的结果证实升高的基因表达水平的淋巴毒素途径包括淋巴毒素α（LTα），淋巴毒素β（LTβ），APOBEC3B（A3B）和APOBEC3G（A3G）在慢性HBV感染肝相比未感染的肝脏。此外，APOBEC脱氨酶家族的基因的表达水平与那些LTα和LTβ基因表达相关，与淋巴毒素介导的APOBEC基因表达的上调一致。然而，肝内cccDNA和HBV复制水平与LTα，LTβ和APOBEC基因表达不相关。总之，这些结果表明，尽管淋巴毒素途径在慢性HBV感染的肝中被激活，但它对慢性HBV感染中的HBV cccDNA代谢没有主要影响。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

APOBEC3;乙型肝炎病毒;人肝活组织检查;淋巴毒素; cccDNA降解

PMID：
    28182305
DOI：
    10.1111 / jvh.12689