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Mapping the Interactions of HBV cccDNA with Host Factors

1
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore 117545, Singapore
2
Department of Medicine, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore 119228, Singapore
3
Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore 138673, Singapore
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(17), 4276; https://doi.org/10.3390/ijms20174276
Received: 6 August 2019 / Revised: 26 August 2019 / Accepted: 27 August 2019 / Published: 1 September 2019
(This article belongs to the Special Issue Molecular Research in Emerging Viruses 2019)
Hepatitis B virus (HBV) infection is a major health problem affecting about 300 million people globally. Although successful administration of a prophylactic vaccine has reduced new infections, a cure for chronic hepatitis B (CHB) is still unavailable. Current anti-HBV therapies slow down disease progression but are not curative as they cannot eliminate or permanently silence HBV covalently closed circular DNA (cccDNA). The cccDNA minichromosome persists in the nuclei of infected hepatocytes where it forms the template for all viral transcription. Interactions between host factors and cccDNA are crucial for its formation, stability, and transcriptional activity. Here, we summarize the reported interactions between HBV cccDNA and various host factors and their implications on HBV replication. While the virus hijacks certain cellular processes to complete its life cycle, there are also host factors that restrict HBV infection. Therefore, we review both positive and negative regulation of HBV cccDNA by host factors and the use of small molecule drugs or sequence-specific nucleases to target these interactions or cccDNA directly. We also discuss several reporter-based surrogate systems that mimic cccDNA biology which can be used for drug library screening of cccDNA-targeting compounds as well as identification of cccDNA-related targets. View Full-Text
Keywords: Hepatitis B virus; covalently closed circular DNA; host-virus interaction; drug target; screening systems Hepatitis B virus; covalently closed circular DNA; host-virus interaction; drug target; screening systems
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MDPI and ACS Style

Mohd-Ismail, N.K.; Lim, Z.; Gunaratne, J.; Tan, Y.-J. Mapping the Interactions of HBV cccDNA with Host Factors. Int. J. Mol. Sci. 2019, 20, 4276.

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