PMID- 32712664 OWN - NLM STAT- MEDLINE DCOM- 20210520 LR - 20210520 IS - 1537-6591 (Electronic) IS - 1058-4838 (Print) IS - 1058-4838 (Linking) VI - 72 IP - 9 DP - 2021 May 4 TI - The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression. PG - e256-e264 LID - 10.1093/cid/ciaa1047 [doi] AB - 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. CI - (c) The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. FAU - Moron-Lopez, Sara AU - Moron-Lopez S AD - AIDS Research Institute IrsiCaixa, Badalona, Spain. FAU - Urrea, Victor AU - Urrea V AD - AIDS Research Institute IrsiCaixa, Badalona, Spain. FAU - Dalmau, Judith AU - Dalmau J AD - AIDS Research Institute IrsiCaixa, Badalona, Spain. FAU - Lopez, Miguel AU - Lopez M AD - Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain. AD - Epigenetic Therapies Group, Experimental and Clinical Hematology Program, Josep Carreras Leukaemia Research Institute, Badalona, Spain. FAU - Puertas, Maria C AU - Puertas MC AD - AIDS Research Institute IrsiCaixa, Badalona, Spain. FAU - Ouchi, Dan AU - Ouchi D AD - AIDS Research Institute IrsiCaixa, Badalona, Spain. FAU - Gomez, Antonio AU - Gomez A AD - Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain. FAU - Passaes, Caroline AU - Passaes C AD - Institut Pasteur, Unite HIV, Inflammation et Persistence, Paris, France. FAU - Mothe, Beatriz AU - Mothe B AD - AIDS Research Institute IrsiCaixa, Badalona, Spain. AD - Fundacio Lluita Contra la Sida, University Hospital "Germans Trias i Pujol," Badalona, Spain. AD - University of Vic-Central University of Catalonia (UVic-UCC), Barcelona, Spain. FAU - Brander, Christian AU - Brander C AD - AIDS Research Institute IrsiCaixa, Badalona, Spain. AD - University of Vic-Central University of Catalonia (UVic-UCC), Barcelona, Spain. AD - Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. FAU - Saez-Cirion, Asier AU - Saez-Cirion A AD - Institut Pasteur, Unite HIV, Inflammation et Persistence, Paris, France. FAU - Clotet, Bonaventura AU - Clotet B AD - AIDS Research Institute IrsiCaixa, Badalona, Spain. AD - Fundacio Lluita Contra la Sida, University Hospital "Germans Trias i Pujol," Badalona, Spain. AD - University of Vic-Central University of Catalonia (UVic-UCC), Barcelona, Spain. FAU - Esteller, Manel AU - Esteller M AD - Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. AD - Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain. AD - Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain. AD - Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Badalona, Spain. FAU - Berdasco, Maria AU - Berdasco M AD - Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain. AD - Epigenetic Therapies Group, Experimental and Clinical Hematology Program, Josep Carreras Leukaemia Research Institute, Badalona, Spain. FAU - Martinez-Picado, Javier AU - Martinez-Picado J AD - AIDS Research Institute IrsiCaixa, Badalona, Spain. AD - University of Vic-Central University of Catalonia (UVic-UCC), Barcelona, Spain. AD - Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. LA - eng GR - P01 AI131568/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Infect Dis JT - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JID - 9203213 SB - IM MH - CD4-Positive T-Lymphocytes MH - Disease Progression MH - *HIV Infections/drug therapy MH - *HIV-1/genetics MH - Humans MH - Viremia PMC - PMC8096268 OTO - NOTNLM OT - HIV-1 disease progression OT - HIV-1 infection OT - TNF OT - genome-wide methylation EDAT- 2020/07/28 06:00 MHDA- 2021/05/21 06:00 PMCR- 2020/07/26 CRDT- 2020/07/27 06:00 PHST- 2020/03/27 00:00 [received] PHST- 2020/07/21 00:00 [accepted] PHST- 2020/07/28 06:00 [pubmed] PHST- 2021/05/21 06:00 [medline] PHST- 2020/07/27 06:00 [entrez] PHST- 2020/07/26 00:00 [pmc-release] AID - 5876587 [pii] AID - ciaa1047 [pii] AID - 10.1093/cid/ciaa1047 [doi] PST - ppublish SO - Clin Infect Dis. 2021 May 4;72(9):e256-e264. doi: 10.1093/cid/ciaa1047.