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Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns

BACKGROUND: Previous epigenome-wide association studies have shown that HIV infection can disrupt the host DNA methylation landscape. However, it remains unclear how antiretroviral therapy (ART) affects the HIV-induced epigenetic modifications. METHODS: 184 individuals with HIV from the NEAT001/ANRS...

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Autores principales: Esteban-Cantos, Andrés, Rodríguez-Centeno, Javier, Silla, Juan C., Barruz, Pilar, Sánchez-Cabo, Fátima, Saiz-Medrano, Gabriel, Nevado, Julián, Mena-Garay, Beatriz, Jiménez-González, María, de Miguel, Rosa, Bernardino, Jose I., Montejano, Rocío, Cadiñanos, Julen, Marcelo, Cristina, Gutiérrez-García, Lucía, Martínez-Martín, Patricia, Wallet, Cédrick, Raffi, François, Rodés, Berta, Arribas, José R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842861/
https://www.ncbi.nlm.nih.gov/pubmed/36640455
http://dx.doi.org/10.1016/j.ebiom.2022.104434
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author Esteban-Cantos, Andrés
Rodríguez-Centeno, Javier
Silla, Juan C.
Barruz, Pilar
Sánchez-Cabo, Fátima
Saiz-Medrano, Gabriel
Nevado, Julián
Mena-Garay, Beatriz
Jiménez-González, María
de Miguel, Rosa
Bernardino, Jose I.
Montejano, Rocío
Cadiñanos, Julen
Marcelo, Cristina
Gutiérrez-García, Lucía
Martínez-Martín, Patricia
Wallet, Cédrick
Raffi, François
Rodés, Berta
Arribas, José R.
author_facet Esteban-Cantos, Andrés
Rodríguez-Centeno, Javier
Silla, Juan C.
Barruz, Pilar
Sánchez-Cabo, Fátima
Saiz-Medrano, Gabriel
Nevado, Julián
Mena-Garay, Beatriz
Jiménez-González, María
de Miguel, Rosa
Bernardino, Jose I.
Montejano, Rocío
Cadiñanos, Julen
Marcelo, Cristina
Gutiérrez-García, Lucía
Martínez-Martín, Patricia
Wallet, Cédrick
Raffi, François
Rodés, Berta
Arribas, José R.
author_sort Esteban-Cantos, Andrés
collection PubMed
description BACKGROUND: Previous epigenome-wide association studies have shown that HIV infection can disrupt the host DNA methylation landscape. However, it remains unclear how antiretroviral therapy (ART) affects the HIV-induced epigenetic modifications. METHODS: 184 individuals with HIV from the NEAT001/ANRS143 clinical trial (with pre-ART and post-ART samples [96 weeks of follow-up]) and 44 age-and-sex matched individuals without HIV were included. We compared genome-wide DNA methylation profiles in whole blood between groups adjusting for age, sex, batch effects, and DNA methylation-based estimates of leucocyte composition. FINDINGS: We identified 430 differentially methylated positions (DMPs) between HIV+ pre-ART individuals and HIV-uninfected controls. In participants with HIV, ART initiation modified the DNA methylation levels at 845 CpG positions and restored 49.3% of the changes found between HIV+ pre-ART and HIV-uninfected individuals. We only found 15 DMPs when comparing DNA methylation profiles between HIV+ post-ART individuals and participants without HIV. The Gene Ontology enrichment analysis of DMPs associated with untreated HIV infection revealed an enrichment in biological processes regulating the immune system and antiviral responses. In participants with untreated HIV infection, DNA methylation levels at top HIV-related DMPs were associated with CD4/CD8 ratios and viral loads. Changes in DNA methylation levels after ART initiation were weakly correlated with changes in CD4+ cell counts and the CD4/CD8 ratio. INTERPRETATION: Control of HIV viraemia after 96 weeks of ART initiation partly restores the host DNA methylation changes that occurred before antiretroviral treatment of HIV infection. FUNDING: NEAT-ID Foundation and 10.13039/501100004587Instituto de Salud Carlos III, co-funded by European Union.
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spelling pubmed-98428612023-01-18 Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns Esteban-Cantos, Andrés Rodríguez-Centeno, Javier Silla, Juan C. Barruz, Pilar Sánchez-Cabo, Fátima Saiz-Medrano, Gabriel Nevado, Julián Mena-Garay, Beatriz Jiménez-González, María de Miguel, Rosa Bernardino, Jose I. Montejano, Rocío Cadiñanos, Julen Marcelo, Cristina Gutiérrez-García, Lucía Martínez-Martín, Patricia Wallet, Cédrick Raffi, François Rodés, Berta Arribas, José R. eBioMedicine Articles BACKGROUND: Previous epigenome-wide association studies have shown that HIV infection can disrupt the host DNA methylation landscape. However, it remains unclear how antiretroviral therapy (ART) affects the HIV-induced epigenetic modifications. METHODS: 184 individuals with HIV from the NEAT001/ANRS143 clinical trial (with pre-ART and post-ART samples [96 weeks of follow-up]) and 44 age-and-sex matched individuals without HIV were included. We compared genome-wide DNA methylation profiles in whole blood between groups adjusting for age, sex, batch effects, and DNA methylation-based estimates of leucocyte composition. FINDINGS: We identified 430 differentially methylated positions (DMPs) between HIV+ pre-ART individuals and HIV-uninfected controls. In participants with HIV, ART initiation modified the DNA methylation levels at 845 CpG positions and restored 49.3% of the changes found between HIV+ pre-ART and HIV-uninfected individuals. We only found 15 DMPs when comparing DNA methylation profiles between HIV+ post-ART individuals and participants without HIV. The Gene Ontology enrichment analysis of DMPs associated with untreated HIV infection revealed an enrichment in biological processes regulating the immune system and antiviral responses. In participants with untreated HIV infection, DNA methylation levels at top HIV-related DMPs were associated with CD4/CD8 ratios and viral loads. Changes in DNA methylation levels after ART initiation were weakly correlated with changes in CD4+ cell counts and the CD4/CD8 ratio. INTERPRETATION: Control of HIV viraemia after 96 weeks of ART initiation partly restores the host DNA methylation changes that occurred before antiretroviral treatment of HIV infection. FUNDING: NEAT-ID Foundation and 10.13039/501100004587Instituto de Salud Carlos III, co-funded by European Union. Elsevier 2023-01-12 /pmc/articles/PMC9842861/ /pubmed/36640455 http://dx.doi.org/10.1016/j.ebiom.2022.104434 Text en © 2022 Fundacion Investigacion Biomedica del Hospital La Paz https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Esteban-Cantos, Andrés
Rodríguez-Centeno, Javier
Silla, Juan C.
Barruz, Pilar
Sánchez-Cabo, Fátima
Saiz-Medrano, Gabriel
Nevado, Julián
Mena-Garay, Beatriz
Jiménez-González, María
de Miguel, Rosa
Bernardino, Jose I.
Montejano, Rocío
Cadiñanos, Julen
Marcelo, Cristina
Gutiérrez-García, Lucía
Martínez-Martín, Patricia
Wallet, Cédrick
Raffi, François
Rodés, Berta
Arribas, José R.
Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns
title Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns
title_full Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns
title_fullStr Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns
title_full_unstemmed Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns
title_short Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns
title_sort effect of hiv infection and antiretroviral therapy initiation on genome-wide dna methylation patterns
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842861/
https://www.ncbi.nlm.nih.gov/pubmed/36640455
http://dx.doi.org/10.1016/j.ebiom.2022.104434
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