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Differences in sequences between HBV-relaxed circular DNA and covalently closed circular DNA

The hepatitis B virus (HBV) genome exists in two forms: circular covalently closed DNA (cccDNA) and relaxed circular DNA (RCDNA). Here, we investigated the presence of differences in the sequences of both forms in paired samples of serum and liver tissue. The serum and liver biopsy samples were coll...

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Autores principales: Rybicka, Magda, Woziwodzka, Anna, Romanowski, Tomasz, Stalke, Piotr, Dręczewski, Marcin, Bielawski, Krzysztof Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520316/
https://www.ncbi.nlm.nih.gov/pubmed/28634352
http://dx.doi.org/10.1038/emi.2017.41
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author Rybicka, Magda
Woziwodzka, Anna
Romanowski, Tomasz
Stalke, Piotr
Dręczewski, Marcin
Bielawski, Krzysztof Piotr
author_facet Rybicka, Magda
Woziwodzka, Anna
Romanowski, Tomasz
Stalke, Piotr
Dręczewski, Marcin
Bielawski, Krzysztof Piotr
author_sort Rybicka, Magda
collection PubMed
description The hepatitis B virus (HBV) genome exists in two forms: circular covalently closed DNA (cccDNA) and relaxed circular DNA (RCDNA). Here, we investigated the presence of differences in the sequences of both forms in paired samples of serum and liver tissue. The serum and liver biopsy samples were collected at the same time from 67 chronically infected patients. The genotyping of the RCDNA and cccDNA was performed using mass spectrometry analysis. The HBV mutations located in the HBV pol (P) and the HBV basal core promoter/pre-core (BCP/PC) regions were included. The BCP/PC and P sequences of the RCDNA extracted from liver and blood samples were different in 39% and 16% of patients, respectively. Differences were also found between RCDNA and cccDNA extracted from the same liver specimen. Moreover, the cccDNA BCP/PC region sequence had an impact on various virological and clinical parameters. We demonstrated that there are differences between the RCDNA and cccDNA sequences that were extracted from the same liver tissue. However, further investigations are needed to analyze whether the mutations in the cccDNA are conserved and whether cccDNA serves as a ‘mutation storage’ pool for HBV. This result could have profound implications for the subsequent therapy choices for treatment-experienced patients.
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spelling pubmed-55203162017-08-21 Differences in sequences between HBV-relaxed circular DNA and covalently closed circular DNA Rybicka, Magda Woziwodzka, Anna Romanowski, Tomasz Stalke, Piotr Dręczewski, Marcin Bielawski, Krzysztof Piotr Emerg Microbes Infect Original Article The hepatitis B virus (HBV) genome exists in two forms: circular covalently closed DNA (cccDNA) and relaxed circular DNA (RCDNA). Here, we investigated the presence of differences in the sequences of both forms in paired samples of serum and liver tissue. The serum and liver biopsy samples were collected at the same time from 67 chronically infected patients. The genotyping of the RCDNA and cccDNA was performed using mass spectrometry analysis. The HBV mutations located in the HBV pol (P) and the HBV basal core promoter/pre-core (BCP/PC) regions were included. The BCP/PC and P sequences of the RCDNA extracted from liver and blood samples were different in 39% and 16% of patients, respectively. Differences were also found between RCDNA and cccDNA extracted from the same liver specimen. Moreover, the cccDNA BCP/PC region sequence had an impact on various virological and clinical parameters. We demonstrated that there are differences between the RCDNA and cccDNA sequences that were extracted from the same liver tissue. However, further investigations are needed to analyze whether the mutations in the cccDNA are conserved and whether cccDNA serves as a ‘mutation storage’ pool for HBV. This result could have profound implications for the subsequent therapy choices for treatment-experienced patients. Nature Publishing Group 2017-06 2017-06-21 /pmc/articles/PMC5520316/ /pubmed/28634352 http://dx.doi.org/10.1038/emi.2017.41 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Rybicka, Magda
Woziwodzka, Anna
Romanowski, Tomasz
Stalke, Piotr
Dręczewski, Marcin
Bielawski, Krzysztof Piotr
Differences in sequences between HBV-relaxed circular DNA and covalently closed circular DNA
title Differences in sequences between HBV-relaxed circular DNA and covalently closed circular DNA
title_full Differences in sequences between HBV-relaxed circular DNA and covalently closed circular DNA
title_fullStr Differences in sequences between HBV-relaxed circular DNA and covalently closed circular DNA
title_full_unstemmed Differences in sequences between HBV-relaxed circular DNA and covalently closed circular DNA
title_short Differences in sequences between HBV-relaxed circular DNA and covalently closed circular DNA
title_sort differences in sequences between hbv-relaxed circular dna and covalently closed circular dna
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520316/
https://www.ncbi.nlm.nih.gov/pubmed/28634352
http://dx.doi.org/10.1038/emi.2017.41
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