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Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals

BACKGROUND: The HIV-1 proviral genome harbors multiple CpG islands (CpGIs), both in the promoter and intragenic regions. DNA methylation in the promoter region has been shown to be heavily involved in HIV-1 latency regulation in cultured cells. However, its exact role in proviral transcriptional reg...

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Autores principales: Kint, Sam, Trypsteen, Wim, De Spiegelaere, Ward, Malatinkova, Eva, Kinloch-de Loes, Sabine, De Meyer, Tim, Van Criekinge, Wim, Vandekerckhove, Linos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049218/
https://www.ncbi.nlm.nih.gov/pubmed/32111236
http://dx.doi.org/10.1186/s13148-020-00829-1
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author Kint, Sam
Trypsteen, Wim
De Spiegelaere, Ward
Malatinkova, Eva
Kinloch-de Loes, Sabine
De Meyer, Tim
Van Criekinge, Wim
Vandekerckhove, Linos
author_facet Kint, Sam
Trypsteen, Wim
De Spiegelaere, Ward
Malatinkova, Eva
Kinloch-de Loes, Sabine
De Meyer, Tim
Van Criekinge, Wim
Vandekerckhove, Linos
author_sort Kint, Sam
collection PubMed
description BACKGROUND: The HIV-1 proviral genome harbors multiple CpG islands (CpGIs), both in the promoter and intragenic regions. DNA methylation in the promoter region has been shown to be heavily involved in HIV-1 latency regulation in cultured cells. However, its exact role in proviral transcriptional regulation in infected individuals is poorly understood or characterized. Moreover, methylation at intragenic CpGIs has never been studied in depth. RESULTS: A large, well-characterized HIV-1 patient cohort (n = 72), consisting of 17 long-term non-progressors and 8 recent seroconverters (SRCV) without combination antiretroviral therapy (cART), 15 early cART-treated, and 32 late cART-treated patients, was analyzed using a next-generation bisulfite sequencing DNA methylation method. In general, we observed low level of promoter methylation and higher levels of intragenic methylation. Additionally, SRCV showed increased promoter methylation and decreased intragenic methylation compared with the other patient groups. This data indicates that increased intragenic methylation could be involved in proviral transcriptional regulation. CONCLUSIONS: Contrasting in vitro studies, our results indicate that intragenic hypermethylation of HIV-1 proviral DNA is an underestimated factor in viral control in HIV-1-infected individuals, showing the importance of analyzing the complete proviral genome in future DNA methylation studies.
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spelling pubmed-70492182020-03-05 Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals Kint, Sam Trypsteen, Wim De Spiegelaere, Ward Malatinkova, Eva Kinloch-de Loes, Sabine De Meyer, Tim Van Criekinge, Wim Vandekerckhove, Linos Clin Epigenetics Research BACKGROUND: The HIV-1 proviral genome harbors multiple CpG islands (CpGIs), both in the promoter and intragenic regions. DNA methylation in the promoter region has been shown to be heavily involved in HIV-1 latency regulation in cultured cells. However, its exact role in proviral transcriptional regulation in infected individuals is poorly understood or characterized. Moreover, methylation at intragenic CpGIs has never been studied in depth. RESULTS: A large, well-characterized HIV-1 patient cohort (n = 72), consisting of 17 long-term non-progressors and 8 recent seroconverters (SRCV) without combination antiretroviral therapy (cART), 15 early cART-treated, and 32 late cART-treated patients, was analyzed using a next-generation bisulfite sequencing DNA methylation method. In general, we observed low level of promoter methylation and higher levels of intragenic methylation. Additionally, SRCV showed increased promoter methylation and decreased intragenic methylation compared with the other patient groups. This data indicates that increased intragenic methylation could be involved in proviral transcriptional regulation. CONCLUSIONS: Contrasting in vitro studies, our results indicate that intragenic hypermethylation of HIV-1 proviral DNA is an underestimated factor in viral control in HIV-1-infected individuals, showing the importance of analyzing the complete proviral genome in future DNA methylation studies. BioMed Central 2020-02-28 /pmc/articles/PMC7049218/ /pubmed/32111236 http://dx.doi.org/10.1186/s13148-020-00829-1 Text en © The Author(s) 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kint, Sam
Trypsteen, Wim
De Spiegelaere, Ward
Malatinkova, Eva
Kinloch-de Loes, Sabine
De Meyer, Tim
Van Criekinge, Wim
Vandekerckhove, Linos
Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals
title Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals
title_full Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals
title_fullStr Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals
title_full_unstemmed Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals
title_short Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals
title_sort underestimated effect of intragenic hiv-1 dna methylation on viral transcription in infected individuals
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049218/
https://www.ncbi.nlm.nih.gov/pubmed/32111236
http://dx.doi.org/10.1186/s13148-020-00829-1
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