乙型肝炎病毒DNA整合：调查病毒发病机理和持久性的体外模

StephenW

Hepatitis B Virus DNA Integration: In Vitro Models for Investigating Viral Pathogenesis and Persistence
Thomas Tu  1   2 , Henrik Zhang  1 , Stephan Urban  3   4
Affiliations
Affiliations

    1
    Storr Liver Centre, Faculty of Medicine and Health, Westmead Clinical School and Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
    2
    Centre for Infectious Diseases and Microbiology, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia.
    3
    Department of Infectious Diseases, Molecular Virology, Heidelberg University Hospital, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
    4
    German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.

    PMID: 33530322 DOI: 10.3390/v13020180

Abstract

Hepatitis B Virus (HBV) is a globally-distributed pathogen and is a major cause of liver disease. HBV (or closely-related animal hepadnaviruses) can integrate into the host genome, but (unlike retroviruses) this integrated form is replication-defective. The specific role(s) of the integrated HBV DNA has been a long-standing topic of debate. Novel in vitro models of HBV infection combined with sensitive molecular assays now enable researchers to investigate this under-characterised phenomenon with greater ease and precision. This review covers the contributions these systems have made to understanding how HBV DNA integration induces liver cancer and facilitates viral persistence. We summarise the current findings into a working model of chronic HBV infection and discuss the clinical implications of this hypothetical framework on the upcoming therapeutic strategies used to curb HBV-associated pathogenesis.

Keywords: HBV DNA integration; HBV double-stranded linear DNA; hepatitis B virus; hepatocellular carcinoma (HCC); microhomology-mediated end joining; non-homologous end joining; viral persistence.

StephenW

乙型肝炎病毒DNA整合：调查病毒发病机理和持久性的体外模型。
托马斯·屠1 2，张子轩1，斯蒂芬·乌尔班3 4
隶属关系
隶属关系

    1个
    悉尼大学韦斯特米德医学院和卫生学院斯托尔肝中心，悉尼大学，韦斯特米德，澳大利亚新南威尔士州2145。
    2
    悉尼大学玛丽·巴希尔传染病与生物安全研究所传染病和微生物学中心，澳大利亚新南威尔士州2145，韦斯特米德，韦斯特米德医院。
    3
    海德堡大学医院分子病毒学传染病科，德国海德堡Im Neuenheimer Feld 345，6912​​0。
    4
    德国感染研究中心（DZIF），海德堡合作伙伴站点，Im Neuenheimer Feld 345，6912​​0海德堡，德国。

    PMID：33530322 DOI：10.3390 / v13020180

抽象

乙型肝炎病毒（HBV）是全球分布的病原体，是肝病的主要原因。 HBV（或密切相关的动物肝炎病毒）可以整合到宿主基因组中，但是（与逆转录病毒不同），这种整合形式具有复制缺陷。整合的HBV DNA的特定作用一直是争论的长期话题。现在，新型的HBV感染体外模型与敏感的分子分析相结合，使研究人员能够更轻松，更准确地研究这种特征不足的现象。这篇综述涵盖了这些系统在理解HBV DNA整合如何诱导肝癌和促进病毒持久性方面所做的贡献。我们将当前的发现总结成一个慢性HBV感染的工作模型，并讨论该假想框架对遏制HBV相关发病机理的即将到来的治疗策略的临床意义。

关键词：HBV DNA整合； HBV双链线性DNA；乙型肝炎病毒;肝细胞癌（HCC）；微同源性介导的末端连接；非同源末端连接；病毒的持久性。

StephenW

https://www.mdpi.com/1999-4915/13/2/180/pdf