乙型肝炎病毒 DNA 整合作为乙型肝炎病毒介导的致病特性的新

StephenW

乙型肝炎病毒 DNA 整合作为乙型肝炎病毒介导的致病特性的新生物标志物和目前乙型肝炎病毒治愈策略的障碍
罗米娜·萨尔皮尼 1 , 斯特凡诺·德安娜 1 , 莉维亚·贝内德蒂 1 , 洛伦佐·皮尔马特奥 1 , 乌普卡·吉尔 2 , 瓦伦蒂娜·史维彻 3 , 帕特里克·T·F·肯尼迪 2
隶属关系
隶属关系

    1
    意大利罗马 Tor Vergata 大学实验医学系。
    2
    Barts Liver Centre, Barts and The London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, 英国。
    3
    意大利罗马 Tor Vergata 大学生物系。

    PMID：36118192 PMCID：PMC9478028 DOI：10.3389/fmicb.2022.972687

抽象的

慢性乙型肝炎病毒 (HBV) 感染是全球肝脏相关发病率和死亡率的主要原因。 HBV-DNA 整合到人类基因组中被认为是 HBV 感染早期阶段经常发生的事件，并表征了 HBV 自然史的整个过程。精细分子生物学技术的发展揭示了 HBV-DNA 整合到人类基因组中的功能意义，包括其在 HBV 相关发病机制进展中的作用，以及在引发促癌机制的建立、促进肝细胞癌。本综述对当前关于 HBV-DNA 整合的知识体系进行了更新和全面的概述，重点关注 HBV-DNA 整合的分子机制及其在 HBV 感染自然史的不同阶段中的发生。此外，我们在这里讨论了 HBV 整合作为 HBV 相关发病机制的生物标志物的主要临床意义，特别是在肝癌发生方面，以及整合如何成为目前和新型抗病毒疗法实现 HBV 治愈的障碍。总体而言，对 HBV 整合的机制和功能进行更精细的了解至关重要，因为它可能为特设诊断工具的设计提供信息，这些工具能够揭示干扰相关细胞内途径的 HBV 整合事件，并用于确定直接针对改变的新治疗策略与 HBV 整合有关。

关键词：HBV生物标志物；乙肝治愈； HBV-DNA整合；慢性乙肝病毒感染；肝细胞癌。

版权所有 © 2022 Salpini、D'Anna、Benedetti、Piermatteo、Gill、Svicher 和 Kennedy。
利益冲突声明

作者声明，该研究是在没有任何可能被解释为潜在利益冲突的商业或财务关系的情况下进行的。

StephenW

Hepatitis B virus DNA integration as a novel biomarker of hepatitis B virus-mediated pathogenetic properties and a barrier to the current strategies for hepatitis B virus cure
Romina Salpini  1 , Stefano D'Anna  1 , Livia Benedetti  1 , Lorenzo Piermatteo  1 , Upkar Gill  2 , Valentina Svicher  3 , Patrick T F Kennedy  2
Affiliations
Affiliations

    1
    Department of Experimental Medicine, University of Rome Tor Vergata, Roma, Italy.
    2
    Barts Liver Centre, Barts and The London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, United Kingdom.
    3
    Department of Biology, University of Rome Tor Vergata, Roma, Italy.

    PMID: 36118192 PMCID: PMC9478028 DOI: 10.3389/fmicb.2022.972687

Abstract

Chronic infection with Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality worldwide. HBV-DNA integration into the human genome is recognized as a frequent event occurring during the early phases of HBV infection and characterizing the entire course of HBV natural history. The development of refined molecular biology technologies sheds new light on the functional implications of HBV-DNA integration into the human genome, including its role in the progression of HBV-related pathogenesis and in triggering the establishment of pro-oncogenic mechanisms, promoting the development of hepatocellular carcinoma. The present review provides an updated and comprehensive overview of the current body of knowledge on HBV-DNA integration, focusing on the molecular mechanisms underlying HBV-DNA integration and its occurrence throughout the different phases characterizing the natural history of HBV infection. Furthermore, here we discuss the main clinical implications of HBV integration as a biomarker of HBV-related pathogenesis, particularly in reference to hepatocarcinogenesis, and how integration may act as a barrier to the achievement of HBV cure with current and novel antiviral therapies. Overall, a more refined insight into the mechanisms and functionality of HBV integration is paramount, since it can potentially inform the design of ad hoc diagnostic tools with the ability to reveal HBV integration events perturbating relevant intracellular pathways and for identifying novel therapeutic strategies targeting alterations directly related to HBV integration.

Keywords: HBV biomarkers; HBV cure; HBV-DNA integration; chronic HBV infection; hepatocellular carcinoma.

Copyright © 2022 Salpini, D’Anna, Benedetti, Piermatteo, Gill, Svicher and Kennedy.
Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

StephenW

https://www.frontiersin.org/arti ... icb.2022.972687/pdf