Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Thursday, 12 / 09 / 2021

Abstract

REVIEW ARTICLE

HBV Integration Induces Complex Interactions between Host and Viral Genomic Functions at the Insertion Site

Dake Zhang1,*, Ke Zhang2,3, Urlike Protzer3,4 and Changqing Zeng5,6

1  Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
2  SCG Cell Therapy Pte. Ltd, Singapore
3  Institute of Virology, Technical University of Munich/Helmholtz Zentrum München, Munich, Germany
4  German Center for Infection Research (DZIF), Munich, Germany
5  Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
6  University of Chinese Academy of Sciences, Beijing, China
*Correspondence to: Dake Zhang, Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. ORCID:  https://orcid.org/0000-0001-9508-8209. E-mail:This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2021;9(3):399-408 DOI: 10.14218/JCTH.2021.00062
Received: February 7, 2021 Accepted: March 31, 2021 Published online: April 25, 2021

Abstract

Hepatitis B virus (HBV), one of the well-known DNA oncogenic viruses, is the leading cause of hepatocellular carcinoma (HCC). In infected hepatocytes, HBV DNA can be integrated into the host genome through an insertional mutagenesis process inducing tumorigenesis. Dissection of the genomic features surrounding integration sites will deepen our understanding of mechanisms underlying integration. Moreover, the quantity and biological activity of integration sites may reflect the DNA damage within affected cells or the potential survival benefits they may confer. The well-known human genomic features include repeat elements, particular regions (such as telomeres), and frequently interrupted genes (e.g., telomerase reverse transcriptase [i.e. TERT], lysine methyltransferase 2B [i.e. KMT2B], cyclin E1 [CCNE1], and cyclin A2 [CCNA2]). Consequently, distinct genomic features within diverse integrations differentiate their biological functions. Meanwhile, accumulating evidence has shown that viral proteins produced by integrants may cause cell damage even after the suppression of HBV replication. The integration-derived gene products can also serve as tumor markers, promoting the development of novel therapeutic strategies for HCC. Viral integrants can be single copy or multiple copies of different fragments with complicated rearrangement, which warrants elucidation of the whole viral integrant arrangement in future studies. All of these considerations underlie an urgent need to develop novel methodology and technology for sequence characterization and function evaluation of integration events in chronic hepatitis B-associated disease progression by monitoring both host genomic features and viral integrants. This endeavor may also serve as a promising solution for evaluating the risk of tumorigenesis and as a companion diagnostic for designing therapeutic strategies targeting integration-related disease complications.

Keywords

Double-strand break, Chimeric reads, Junction reads, Fusion transcript, Virus cellular junction, Virus cell junction, Virus host junction

Journal of Clinical and Translational Hepatology 2021 vol. 9, 399-408  [ Html  ] [ PDF Full-text ]

© 2021 Authors. This is an Open Access article distributed under the terms of the  Creative Commons Attribution-Noncommercial 4.0 License(CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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