Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Sci Rep. 2019 Jul 19;9(1):10495. doi: 10.1038/s41598-019-46930-1.
Perinatally-acquired HIV has persistent effects on long-term health outcomes, even after early treatment. We hypothesize that epigenetic indicators, such as DNA methylation, may elucidate cellular processes that explain these effects. Here, we compared DNA methylation profiles in whole blood from 120 HIV-infected children on antiretroviral therapy (ART) and 60 frequency age-matched HIV-uninfected children aged 4-9 years in Johannesburg, South Africa. Using an individual CpG site approach, we found 1,309 differentially-methylated (DM) CpG sites between groups, including 1,271 CpG sites that were hyper-methylated in the HIV-infected group and 38 CpG sites that were hypo-methylated in the HIV-infected group. Six hyper-methylated CpG sites were in EBF4, which codes for a transcription factor involved in B-cell maturation. The top hypomethylated site was in the promoter region of NLRC5, encoding a transcription factor that regulates major histocompatibility complex (MHC) class I molecule expression. Using a differentially-methylated region (DMR) approach, we found 315 DMRs between groups, including 28 regions encompassing 686 CpG sites on chromosome 6. A large number of the genes identified in both the CpG site and DMR approaches were located in the MHC region on chromosome 6, which plays an important role in the adaptive immune system. This study provides the first evidence that changes in the epigenome are detectable in children with perinatally-acquired HIV infection on suppressive ART started at an early age.
围生期获得性 HIV 对长期健康结果有持续影响，即使在早期治疗后也是如此。我们假设表观遗传标志物，如 DNA 甲基化，可能阐明解释这些影响的细胞过程。在这里，我们比较了南非约翰内斯堡 120 名接受抗逆转录病毒治疗 (ART) 的 HIV 感染儿童和 60 名年龄匹配的 HIV 未感染儿童的全血 DNA 甲基化谱。使用个体 CpG 位点方法，我们发现两组之间有 1309 个差异甲基化 (DM) CpG 位点，包括 1271 个在 HIV 感染组中高甲基化的 CpG 位点和 38 个在 HIV 感染组中低甲基化的 CpG 位点。EBF4 中有 6 个高甲基化 CpG 位点，其编码参与 B 细胞成熟的转录因子。高甲基化的 CpG 位点在 NLRC5 的启动子区域，编码一种调节主要组织相容性复合体 (MHC) Ⅰ类分子表达的转录因子。使用差异甲基化区域 (DMR) 方法，我们发现两组之间有 315 个 DMR，包括染色体 6 上 28 个包含 686 个 CpG 位点的区域。在 CpG 位点和 DMR 方法中鉴定的大量基因位于染色体 6 上的 MHC 区域，该区域在适应性免疫系统中起着重要作用。这项研究首次提供了证据，表明在早期开始接受抑制性 ART 的围生期获得性 HIV 感染儿童的表观基因组中可以检测到变化。
