临床中的HBV整合研究：在自然感染史中的作用

StephenW

HBV-Integration Studies in the Clinic: Role in the Natural History of Infection
Teresa Pollicino  1 , Giuseppe Caminiti  2
Affiliations
Affiliations

    1
    Laboratory of Molecular Hepatology, Department of Human Pathology, University Hospital "G. Martino" of Messina, 98124 Messina, Italy.
    2
    Laboratory of Molecular Hepatology, Department of Human Pathology, University of Messina, 98124 Messina, Italy.

    PMID: 33652619 DOI: 10.3390/v13030368

Abstract

Hepatitis B virus (HBV) infection is a major global health problem causing acute and chronic liver disease that can lead to liver cirrhosis and hepatocellular carcinoma (HCC). HBV covalently closed circular DNA (cccDNA) is essential for viral replication and the establishment of a persistent infection. Integrated HBV DNA represents another stable form of viral DNA regularly observed in the livers of infected patients. HBV DNA integration into the host genome occurs early after HBV infection. It is a common occurrence during the HBV life cycle, and it has been detected in all the phases of chronic infection. HBV DNA integration has long been considered to be the main contributor to liver tumorigenesis. The recent development of highly sensitive detection methods and research models has led to the clarification of some molecular and pathogenic aspects of HBV integration. Though HBV integration does not lead to replication-competent transcripts, it can act as a stable source of viral RNA and proteins, which may contribute in determining HBV-specific T-cell exhaustion and favoring virus persistence. The relationship between HBV DNA integration and the immune response in the liver microenvironment might be closely related to the development and progression of HBV-related diseases. While many new antiviral agents aimed at cccDNA elimination or silencing have been developed, integrated HBV DNA remains a difficult therapeutic challenge.

Keywords: HBV DNA integration; HBsAg; HBx; chronic hepatitis B; double-stranded DNA breaks; hepatitis B virus infection; oxidative stress.

StephenW

临床中的HBV整合研究：在自然感染史中的作用
特蕾莎·波里奇诺（Teresa Pollicino）1，朱塞佩·卡米尼蒂（Giuseppe Caminiti）2
隶属关系
隶属关系

    1个
    意大利墨西拿大学医院“ G. Martino”人体病理学部分子肝病实验室，意大利98124。
    2个
    墨西拿大学人类病理学系分子肝病实验室，意大利墨西拿98124。

    PMID：33652619 DOI：10.3390 / v13030368

抽象的

乙型肝炎病毒（HBV）感染是引起急性和慢性肝病的主要全球性健康问题，可能导致肝硬化和肝细胞癌（HCC）。 HBV共价封闭的环状DNA（cccDNA）对于病毒复制和持续感染的建立至关重要。整合的HBV DNA代表了在感染患者的肝脏中定期观察到的另一种稳定形式的病毒DNA。 HBV DNA整合入宿主基因组发生在HBV感染后的早期。它是HBV生命周期中的常见现象，并且已在慢性感染的所有阶段中被检测到。长期以来，HBV DNA整合一直被认为是肝肿瘤发生的主要因素。高灵敏度检测方法和研究模型的最新发展已导致对HBV整合的某些分子和病原学方面的澄清。尽管HBV整合并不能产生具有复制能力的转录本，但它可以作为病毒RNA和蛋白质的稳定来源，这可能有助于确定HBV特异性T细胞的耗竭并有利于病毒的持久性。 HBV DNA整合与肝脏微环境中的免疫反应之间的关系可能与HBV相关疾病的发生和发展密切相关。尽管已经开发出了许多针对cccDNA消除或沉默的新型抗病毒药物，但整合的HBV DNA仍然是一项艰巨的治疗挑战。

关键词：HBV DNA整合；乙肝表面抗原HBx;慢性乙型肝炎双链DNA断裂；乙肝病毒感染；氧化应激。

StephenW

https://pubmed.ncbi.nlm.nih.gov/33652619/