对乙型肝炎病毒 DNA 整合的洞察 - 病毒发现 55 年后

StephenW

对乙型肝炎病毒 DNA 整合的洞察 - 病毒发现 55 年后赵开涛 1 , Andrew Liu 2 , 夏雨辰 1隶属关系隶属关系    1    武汉大学基础医学院，病毒学国家重点实验室，湖北省变态反应与免疫学重点实验室，武汉 430071。    2    分子心脏病学实验室，国家心肺血液研究所，美国国立卫生研究院，贝塞斯达，MD 20814，美国。    PMID：34557710 PMCID：PMC8454683 DOI：10.1016/j.xinn.2020.100034抽象的乙型肝炎病毒 (HBV) 于 1965 年被发现，对全球公共卫生构成威胁。 HBV感染人肝细胞，导致急慢性肝病，目前尚无治愈方法。在被HBV感染的细胞中，病毒DNA可以整合到细胞基因组中。 HBV DNA 整合是 HBV 生命周期中的一个复杂过程。尽管 HBV 整合通常会导致无法复制的转录本，但它仍然可以作为病毒蛋白表达的模板。值得注意的是，它是肝细胞癌 (HCC) 的主要驱动因素。近年来，随着检测方法和研究模型的发展，HBV DNA整合的分子生物学和致病性得到更好的揭示。在这里，我们回顾了HBV DNA整合研究的进展，包括分子机制、检测方法、研究模型、对宿主和病毒基因表达的影响、HBV整合在HCC发病机制中的作用以及潜在的治疗策略。最后，我们讨论了HBV DNA整合未来可能的研究前景。关键词：乙肝病毒；肝细胞癌;插入诱变；一体化;非同源末端连接。© 2020 作者。

StephenW

Insights into Hepatitis B Virus DNA Integration-55 Years after Virus Discovery
Kaitao Zhao  1 , Andrew Liu  2 , Yuchen Xia  1
Affiliations
Affiliations

    1
    State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
    2
    Laboratory of Molecular Cardiology, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20814, USA.

    PMID: 34557710 PMCID: PMC8454683 DOI: 10.1016/j.xinn.2020.100034

Abstract

Hepatitis B virus (HBV), which was discovered in 1965, is a threat to global public health. HBV infects human hepatocytes and leads to acute and chronic liver diseases, and there is no cure. In cells infected by HBV, viral DNA can be integrated into the cellular genome. HBV DNA integration is a complicated process during the HBV life cycle. Although HBV integration normally results in replication-incompetent transcripts, it can still act as a template for viral protein expression. Of note, it is a primary driver of hepatocellular carcinoma (HCC). Recently, with the development of detection methods and research models, the molecular biology and the pathogenicity of HBV DNA integration have been better revealed. Here, we review the advances in the research of HBV DNA integration, including molecular mechanisms, detection methods, research models, the effects on host and viral gene expression, the role of HBV integrations in the pathogenesis of HCC, and potential treatment strategies. Finally, we discuss possible future research prospects of HBV DNA integration.

Keywords: hepatitis B virus; hepatocellular carcinoma; insertional mutagenesis; integration; non-homologous end joining.

© 2020 The Authors.

StephenW

https://www.cell.com/the-innovation/pdf/S2666-6758(20)30034-5.pdf