在开始抗逆转录病毒治疗之前，人类免疫缺陷病毒感染中出现的加速表观遗传衰老和甲基化紊乱。
Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy.
机构信息
Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
出版信息
J Infect Dis. 2021 May 28;223(10):1681-1689. doi: 10.1093/infdis/jiaa599.
BACKGROUND
Whether accelerated aging develops over the course of chronic human immunodeficiency virus (HIV) infection or can be observed before significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) before the initiation of antiretroviral therapy (ART).
METHODS
A total of 378 ART-naive PLWH who had CD4 T-cell counts >500/µL and were enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared with 34 HIV-negative controls. DNA methylation was performed using the Illumina MethylationEPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in PLWH compared with controls were identified using a robust linear model. Methylation age was calculated using a previously described epigenetic clock.
RESULTS
There were a total of 56 639 DMPs and 6103 DMRs at a false discovery rate of <0.1. The top 5 DMPs corresponded to genes NLRC5, VRK2, B2M, and GPR6 and were highly enriched for cancer-related pathways. PLWH had significantly higher methylation age than HIV-negative controls (P = .001), with black race, low CD4 and high CD8 T-cell counts, and duration of HIV being risk factors for age acceleration.
CONCLUSIONS
PLWH before the initiation of ART and with preserved immune status show evidence of advanced methylation aging.
背景
慢性人类免疫缺陷病毒（HIV）感染过程中是否会发生加速衰老，或者在出现明显免疫抑制之前是否可以观察到，目前尚不清楚。我们研究了 HIV 感染者（PLWH）在开始抗逆转录病毒治疗（ART）之前血液中的 DNA 甲基化情况，以评估其细胞衰老情况。
方法
共有 378 名 CD4 T 细胞计数>500/µL、未接受过 ART 的 PLWH 参加了抗逆转录病毒治疗时机的策略性研究（肺部子研究），并与 34 名 HIV 阴性对照进行了比较。使用 Illumina MethylationEPIC BeadChip 进行 DNA 甲基化分析。采用稳健的线性模型鉴定 PLWH 与对照组之间的差异甲基化位置（DMP）和差异甲基化区域（DMR）。使用先前描述的表观遗传时钟计算甲基化年龄。
结果
在错误发现率<0.1 时，共鉴定出 56639 个 DMP 和 6103 个 DMR。前 5 个 DMP 对应 NLRC5、VRK2、B2M 和 GPR6 基因，高度富集于癌症相关途径。PLWH 的甲基化年龄明显高于 HIV 阴性对照组（P=0.001），黑种人、低 CD4 和高 CD8 T 细胞计数以及 HIV 持续时间是加速衰老的危险因素。
结论
在开始 ART 且免疫状态良好的 PLWH 中，存在先进的甲基化衰老证据。
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