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A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?
Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-li...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454437/ https://www.ncbi.nlm.nih.gov/pubmed/28531167 http://dx.doi.org/10.3390/v9050125 |
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author | Schreiner, Sabrina Nassal, Michael |
author_facet | Schreiner, Sabrina Nassal, Michael |
author_sort | Schreiner, Sabrina |
collection | PubMed |
description | Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is converted into nuclear covalently closed circular (ccc) DNA. Associating with cellular proteins into an episomal minichromosome, cccDNA acts as template for new viral RNAs, ensuring formation of progeny virions. Hence, cccDNA represents the viral persistence reservoir that is not directly targeted by current anti-HBV therapeutics. Eliminating cccDNA will thus be at the heart of a cure for chronic hepatitis B. The low production of HBV cccDNA in most experimental models and the associated problems in reliable cccDNA quantitation have long hampered a deeper understanding of cccDNA molecular biology. Recent advancements including cccDNA-dependent cell culture systems have begun to identify select host DNA repair enzymes that HBV usurps for RC-DNA to cccDNA conversion. While this list is bound to grow, it may represent just one facet of a broader interaction with the cellular DNA damage response (DDR), a network of pathways that sense and repair aberrant DNA structures and in the process profoundly affect the cell cycle, up to inducing cell death if repair fails. Given the divergent interactions between other viruses and the DDR it will be intriguing to see how HBV copes with this multipronged host system. |
format | Online Article Text |
id | pubmed-5454437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-54544372017-06-08 A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond? Schreiner, Sabrina Nassal, Michael Viruses Review Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is converted into nuclear covalently closed circular (ccc) DNA. Associating with cellular proteins into an episomal minichromosome, cccDNA acts as template for new viral RNAs, ensuring formation of progeny virions. Hence, cccDNA represents the viral persistence reservoir that is not directly targeted by current anti-HBV therapeutics. Eliminating cccDNA will thus be at the heart of a cure for chronic hepatitis B. The low production of HBV cccDNA in most experimental models and the associated problems in reliable cccDNA quantitation have long hampered a deeper understanding of cccDNA molecular biology. Recent advancements including cccDNA-dependent cell culture systems have begun to identify select host DNA repair enzymes that HBV usurps for RC-DNA to cccDNA conversion. While this list is bound to grow, it may represent just one facet of a broader interaction with the cellular DNA damage response (DDR), a network of pathways that sense and repair aberrant DNA structures and in the process profoundly affect the cell cycle, up to inducing cell death if repair fails. Given the divergent interactions between other viruses and the DDR it will be intriguing to see how HBV copes with this multipronged host system. MDPI 2017-05-22 /pmc/articles/PMC5454437/ /pubmed/28531167 http://dx.doi.org/10.3390/v9050125 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Schreiner, Sabrina Nassal, Michael A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond? |
title | A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond? |
title_full | A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond? |
title_fullStr | A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond? |
title_full_unstemmed | A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond? |
title_short | A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond? |
title_sort | role for the host dna damage response in hepatitis b virus cccdna formation—and beyond? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454437/ https://www.ncbi.nlm.nih.gov/pubmed/28531167 http://dx.doi.org/10.3390/v9050125 |
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