Zhao Kaitao, Liu Andrew, Xia Yuchen
State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Laboratory of Molecular Cardiology, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20814, USA.
Innovation (Camb). 2020 Aug 5;1(2):100034. doi: 10.1016/j.xinn.2020.100034. eCollection 2020 Aug 28.
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.
乙肝病毒(HBV)于1965年被发现,是对全球公共卫生的一种威胁。HBV感染人类肝细胞并导致急慢性肝病,且无法治愈。在被HBV感染的细胞中,病毒DNA可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。虽然HBV整合通常会产生无复制能力的转录本,但它仍可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了更好的揭示。在此,我们综述了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。