The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression

Author:

Moron-Lopez Sara1,Urrea Victor1,Dalmau Judith1,Lopez Miguel23,Puertas Maria C1,Ouchi Dan1,Gómez Antonio2,Passaes Caroline4,Mothe Beatriz156,Brander Christian167,Saez-Cirion Asier4,Clotet Bonaventura156,Esteller Manel78910,Berdasco Maria23,Martinez-Picado Javier167

Affiliation:

1. AIDS Research Institute IrsiCaixa, Badalona, Spain

2. Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain

3. Epigenetic Therapies Group, Experimental and Clinical Hematology Program, Josep Carreras Leukaemia Research Institute, Badalona, Spain

4. Institut Pasteur, Unité HIV, Inflammation et Persistence, Paris, France

5. Fundació Lluita Contra la Sida, University Hospital “Germans Trias i Pujol,” Badalona, Spain

6. University of Vic-Central University of Catalonia (UVic-UCC), Barcelona, Spain

7. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain

8. Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain

9. Centro de Investigación Biomédica en Red Cancer (CIBERONC), Madrid, Spain

10. Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Badalona, Spain

Abstract

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.

Funder

Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund

Instituto de Salud Carlos III

European Regional Development Fund

European Social Fund

European Union’s Horizon 2020

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Gilead Sciences

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Reference40 articles.

1. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load;McLaren;Proc Natl Acad Sci USA,2015

2. DNA methylation and control of gene expression;Lindahl;Nature,1981

3. Epigenetics and animal virus infections;Galvan;Front Genet,2015

4. The early expressed HIV-1 genes regulate DNMT1 expression;Youngblood;Epigenetics,2008

5. Epigenetic regulation of HIV-1 latency by cytosine methylation;Kauder;PLoS Pathog,2009

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