HBV Transcriptional and Post-transcriptional Regulation
A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".
Deadline for manuscript submissions: closed (15 July 2024) | Viewed by 12504
Special Issue Editors
Interests: hepatitis B virus; hepatitis delta virus; HBx; RNA therapies; antisense oligonucleotide therapies
Special Issue Information
Dear Colleagues,
Hepatitis B virus (HBV), a small, enveloped DNA virus from the hepadnaviridae family, contuinues to be a major public health concern, with approximately 300 million people chronically infected worldwide. Covalently closed circular HBV DNA (cccDNA) is the stable, chromatinized, episomal viral genome, which encodes two enhancers and four promoters and serves as the transcriptional template for six viral RNAs (preCore, pre-genomic (pg), preS1/S2, S, HBx). Besides these major HBV RNAs, at least 20 variants of spliced pgRNA and several HBx transcripts of varying lengths are also produced, though their functions remain mostly undefined.
HBV cccDNA exists in the nucleus as a “minichromosome” associated with histones and various other host proteins. Viral transcription is dependent on the cellular transcriptional machinery and recent studies indicate that cccDNA is controlled by host epigenetic regulatory mechanisms. For example, histone acetyltransferases, the histone-lysine N-methyltransferase SETDB1, the arginine methyltransferase PRMT1, and the structural maintenance of chromosome 5/6 complex (Smc5/6) have been reported to modulate HBV transcription. HBV RNAs are also regulated post-transcriptionally, e.g., by the TENT4-ZCCHC14 complex.
Nucleos(t)ide inhibitors of HBV replication do not directly impact cccDNA transcription or reduce HBV RNA levels. Therefore, new antiviral therapies are being developed to inhibit cccDNA transcription or to target HBV RNAs. These include HBV-targeted antisense oligonucleotides and siRNAs, as well as inhibitors of the viral HBx protein, and inhibitors of host targets such as histone modifying enzymes and TENT4A/4B. The potential of capsid assembly modulators (CAMs) to module HBV transcription also continues to be explored.
This Special Issue aims to update recent advances in the field of HBV transcriptional and post-transcriptional regulation, including furthering our understanding of:
- Epigenetic regulation of HBV transcription;
- Host restriction of HBV transcription;
- HBV RNA splicing;
- HBV RNA stabilization/degradation;
- Advances in antiviral therapies targeting HBV transcription and HBV RNAs.
Dr. Rudolf K. Beran
Dr. Simon P. Fletcher
Guest Editors
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Keywords
- cccDNA
- epigenetic regulation
- SMC5/6 complex
- HBx
- RNA splicing
- TENT4A/B (PAPD5/7)
- interferon
- Interferon-Stimulated Genes (ISGs)
- antisense oligonucleotide
- siRNA
- CAM
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