The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression.
The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression.
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DOI：
10.1093/cid/ciaa1047
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发表时间：
2021-05-04
期刊：
影响因子：
--
通讯作者：
Martinez-Picado J
中科院分区：
文献类型：
--
作者：
Moron-Lopez S;Urrea V;Dalmau J;Lopez M;Puertas MC;Ouchi D;Gómez A;Passaes C;Mothe B;Brander C;Saez-Cirion A;Clotet B;Esteller M;Berdasco M;Martinez-Picado J
人类遗传变异-主要是在人类白细胞抗原（HLA）和C-C趋化因子受体5型（CCR 5）区域-解释了人类免疫缺陷病毒（HIV）感染进展中25%的变异性。然而，也已知病毒感染可以改变细胞DNA甲基化模式。因此，胞嘧啶-鸟嘌呤（CpG）岛甲基化的变化可能调节HIV感染的进展。总共分析了85份样本：21名精英控制者（EC），21名在联合抗逆转录病毒治疗（cART）之前患有HIV的受试者（病毒血症，93325人类免疫缺陷病毒1型[HIV-1] RNA拷贝/mL）和抑制性cART（cART，中位数为17个月，<50 HIV-1 RNA拷贝/mL），以及22名HIV阴性供体（HIV阴性）。我们分析了外周血CD 4 + T淋巴细胞DNA中485 577个CpG的甲基化模式。我们选择了甲基化差异最大的基因（TNF），并分析了5名个体在cART开始前后的特异性甲基化、信使RNA（mRNA）表达和血浆蛋白水平。我们观察到129个甲基化的CpG位点（与43个基因启动子相关），其中在病毒血症与HIV阴性中记录了统计学显著差异，在病毒血症与cART中记录了162个CpG位点（55个基因启动子），在病毒血症与EC中记录了441个CpG位点（163个基因启动子），但在EC与HIV阴性中没有。TNF启动子区域在病毒血症与HIV阴性、cART和EC中高甲基化。此外，我们观察到病毒血症个体的TNF血浆水平高于EC、cART和HIV阴性个体。我们的研究表明，基因组甲基化模式根据HIV感染状态和进展情况而变化，这些变化可能对在没有cART的情况下控制HIV感染产生影响。这项研究表明，非人类免疫缺陷病毒（HIV）感染和病毒血症，联合抗逆转录病毒治疗（cART）抑制，和精英控制者与HIV个体之间的基因组甲基化模式取决于HIV病毒血症和进展概况，这可能会影响在没有cART的情况下控制HIV感染。
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. 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. 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. 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. This study shows that genome methylation patterns among nonhuman immunodeficiency virus (HIV)-infected and viremic, combination antiretroviral therapy (cART)-suppressed, and elite controller individuals with HIV vary depending on HIV viremia and progression profile, which might have an impact on control of HIV infection in the absence of cART.
影响因子：
4.2
作者：
Bettaccini AA;Baj A;Accolla RS;Basolo F;Toniolo AQ
通讯作者：
Toniolo AQ
影响因子：
3.4
作者：
Britton, Laura-Mae P.;Sova, Pavel;Belisle, Sarah;Liu, Shichong;Chan, Eric Y.;Katze, Michael G.;Garcia, Benjamin A.
通讯作者：
Garcia, Benjamin A.