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Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
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Strategies to Inhibit Hepatitis B Virus at the Transcript Level
Bingqian Qu1,2, Richard J P Brown1
1Division of Veterinary Medicine, Paul Ehrlich Institute, 63225 Langen, Germany.
Viruses
|August 10, 2021
Summary
New antivirals target hepatitis B virus (HBV) transcription and transcripts. These drugs, including nuclear receptor agonists and RNA-based therapies, show promise in reducing viral load and surface antigen expression for HBV treatment.
Area of Science:
- Hepatology and Viral Immunology
- Molecular Virology and Drug Discovery
Background:
- Chronic hepatitis B virus (HBV) infection affects approximately 240 million people globally.
- HBV transcription relies on episomal covalently closed circular DNA (cccDNA) and integrated viral DNA.
- Viral gene transcription is modulated by various liver-specific and ubiquitous transcription factors.
Purpose of the Study:
- To review recent advancements in antiviral therapies targeting HBV gene transcription and transcript stability.
- To highlight novel therapeutic strategies for managing chronic HBV infection.
Main Methods:
- Review of current literature on antivirals affecting HBV transcription and transcript degradation.
- Analysis of mechanisms of action for nuclear receptor agonists, small molecule inhibitors, and RNA-based therapeutics (siRNAs, oligonucleotides).
- Evaluation of the impact of these antivirals on viral transcripts and surface antigen expression.
Main Results:
- Nuclear receptor agonists effectively inhibit HBV gene transcription from cccDNA.
- Small molecule inhibitors repress HBV X protein-mediated transcription.
- Small interfering RNAs and single-stranded oligonucleotides degrade viral transcripts from both cccDNA and integrated templates, reducing viral load and surface antigen expression.
Conclusions:
- Emerging antivirals demonstrate potent inhibition of HBV transcription and transcript destabilization.
- These agents reduce viral RNA abundance and can lead to loss of surface antigen expression.
- These novel therapeutics hold significant potential for repurposing or further development in anti-HBV drug arsenals.
Keywords:
RNA interferencechronic hepatitis Bcovalently closed circular DNAnuclear receptortranscription factortranscriptional inhibitorviral integrationMore Related Videos
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