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The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression
Moron-Lopez, Sara (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Urrea, Víctor (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Dalmau, Judith (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Lopez, Miguel (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Puertas, Maria C.. (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ouchi, Dan (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Gómez Moruno, Antonio (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Passaes, Caroline (Institut Pasteur)
Mothe, Beatriz (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Brander, Christian (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Saez-Cirion, Asier (Institut Pasteur)
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Fundació de Lluita Contra la Sida)
Esteller, M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Berdasco, Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Martinez-Picado, Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)

Date: 2021
Abstract: BACKGROUND: Human genetic variation-mostly in the human leukocyte antigen (HLA) and C-C chemokine receptor type 5 (CCR5) regions-explains 25% of the variability in progression of human immunodeficiency virus (HIV) infection. However, it is also known that viral infections can modify cellular DNA methylation patterns. Therefore, changes in the methylation of cytosine-guanine (CpG) islands might modulate progression of HIV infection. METHODS: In total, 85 samples were analyzed: 21 elite controllers (EC), 21 subjects with HIV before combination antiretroviral therapy (cART) (viremic, 93 325 human immunodeficiency virus type 1 [HIV-1] RNA copies/mL) and under suppressive cART (cART, median of 17 months, <50 HIV-1 RNA copies/mL), and 22 HIV-negative donors (HIVneg). We analyzed the methylation pattern of 485 577 CpG in DNA from peripheral CD4+ T lymphocytes. We selected the most differentially methylated gene (TNF) and analyzed its specific methylation, messenger RNA (mRNA) expression, and plasma protein levels in 5 individuals before and after initiation of cART. RESULTS: We observed 129 methylated CpG sites (associated with 43 gene promoters) for which statistically significant differences were recorded in viremic versus HIVneg, 162 CpG sites (55 gene promoters) in viremic versus cART, 441 CpG sites (163 gene promoters) in viremic versus EC, but none in EC versus HIVneg. The TNF promoter region was hypermethylated in viremic versus HIVneg, cART, and EC. Moreover, we observed greater plasma levels of TNF in viremic individuals than in EC, cART, and HIVneg. CONCLUSIONS: Our study shows that genome methylation patterns vary depending on HIV infection status and progression profile and that these variations might have an impact on controlling HIV infection in the absence of cART.
Grants: Ministerio de Economía y Competitividad SAF2016-80033-R
Instituto de Salud Carlos III RD12/0017/0002
Instituto de Salud Carlos III RD16/0025/0041
Agència de Gestió d'Ajuts Universitaris i de Recerca 2013FI_B 00275
European Commission 681137
Note: Altres ajuts: National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number PO1-AI131568
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Subject: Genome-wide methylation ; HIV-1 infection ; HIV-1 disease progression ; TNF
Published in: Clinical Infectious Diseases, Vol. 72 Núm. 9 (april 2021) , p. e256-e264, ISSN 1537-6591

DOI: 10.1093/cid/ciaa1047
PMID: 32712664


9 p, 3.7 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles

 Record created 2021-06-15, last modified 2023-11-05



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