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G-quadruplexes in the evolution of hepatitis B virus

Hepatitis B virus (HBV) is one of the most dangerous human pathogenic viruses found in all corners of the world. Recent sequencing of ancient HBV viruses revealed that these viruses have accompanied humanity for several millenia. As G-quadruplexes are considered to be potential therapeutic targets i...

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Autores principales: Brázda, Václav, Dobrovolná, Michaela, Bohálová, Natália, Mergny, Jean-Louis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415126/
https://www.ncbi.nlm.nih.gov/pubmed/37395407
http://dx.doi.org/10.1093/nar/gkad556
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author Brázda, Václav
Dobrovolná, Michaela
Bohálová, Natália
Mergny, Jean-Louis
author_facet Brázda, Václav
Dobrovolná, Michaela
Bohálová, Natália
Mergny, Jean-Louis
author_sort Brázda, Václav
collection PubMed
description Hepatitis B virus (HBV) is one of the most dangerous human pathogenic viruses found in all corners of the world. Recent sequencing of ancient HBV viruses revealed that these viruses have accompanied humanity for several millenia. As G-quadruplexes are considered to be potential therapeutic targets in virology, we examined G-quadruplex-forming sequences (PQS) in modern and ancient HBV genomes. Our analyses showed the presence of PQS in all 232 tested HBV genomes, with a total number of 1258 motifs and an average frequency of 1.69 PQS per kbp. Notably, the PQS with the highest G4Hunter score in the reference genome is the most highly conserved. Interestingly, the density of PQS motifs is lower in ancient HBV genomes than in their modern counterparts (1.5 and 1.9/kb, respectively). This modern frequency of 1.90 is very close to the PQS frequency of the human genome (1.93) using identical parameters. This indicates that the PQS content in HBV increased over time to become closer to the PQS frequency in the human genome. No statistically significant differences were found between PQS densities in HBV lineages found in different continents. These results, which constitute the first paleogenomics analysis of G4 propensity, are in agreement with our hypothesis that, for viruses causing chronic infections, their PQS frequencies tend to converge evolutionarily with those of their hosts, as a kind of ‘genetic camouflage’ to both hijack host cell transcriptional regulatory systems and to avoid recognition as foreign material.
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spelling pubmed-104151262023-08-12 G-quadruplexes in the evolution of hepatitis B virus Brázda, Václav Dobrovolná, Michaela Bohálová, Natália Mergny, Jean-Louis Nucleic Acids Res Computational Biology Hepatitis B virus (HBV) is one of the most dangerous human pathogenic viruses found in all corners of the world. Recent sequencing of ancient HBV viruses revealed that these viruses have accompanied humanity for several millenia. As G-quadruplexes are considered to be potential therapeutic targets in virology, we examined G-quadruplex-forming sequences (PQS) in modern and ancient HBV genomes. Our analyses showed the presence of PQS in all 232 tested HBV genomes, with a total number of 1258 motifs and an average frequency of 1.69 PQS per kbp. Notably, the PQS with the highest G4Hunter score in the reference genome is the most highly conserved. Interestingly, the density of PQS motifs is lower in ancient HBV genomes than in their modern counterparts (1.5 and 1.9/kb, respectively). This modern frequency of 1.90 is very close to the PQS frequency of the human genome (1.93) using identical parameters. This indicates that the PQS content in HBV increased over time to become closer to the PQS frequency in the human genome. No statistically significant differences were found between PQS densities in HBV lineages found in different continents. These results, which constitute the first paleogenomics analysis of G4 propensity, are in agreement with our hypothesis that, for viruses causing chronic infections, their PQS frequencies tend to converge evolutionarily with those of their hosts, as a kind of ‘genetic camouflage’ to both hijack host cell transcriptional regulatory systems and to avoid recognition as foreign material. Oxford University Press 2023-07-03 /pmc/articles/PMC10415126/ /pubmed/37395407 http://dx.doi.org/10.1093/nar/gkad556 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Computational Biology
Brázda, Václav
Dobrovolná, Michaela
Bohálová, Natália
Mergny, Jean-Louis
G-quadruplexes in the evolution of hepatitis B virus
title G-quadruplexes in the evolution of hepatitis B virus
title_full G-quadruplexes in the evolution of hepatitis B virus
title_fullStr G-quadruplexes in the evolution of hepatitis B virus
title_full_unstemmed G-quadruplexes in the evolution of hepatitis B virus
title_short G-quadruplexes in the evolution of hepatitis B virus
title_sort g-quadruplexes in the evolution of hepatitis b virus
topic Computational Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415126/
https://www.ncbi.nlm.nih.gov/pubmed/37395407
http://dx.doi.org/10.1093/nar/gkad556
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