School of Life Sciences, Shanghai University, Shanghai, 200444, China.
Shanghai Key Laboratory of PMMP, East China Normal University, Shanghai, 200241, China.
Gene Ther. 2019 Feb;26(1-2):29-39. doi: 10.1038/s41434-018-0051-6. Epub 2018 Nov 15.
Many complex diseases or traits are the results of both genetic and environmental factors. The environmental factors affect the human body by modifying its epigenetics, which controls the activity of genomes without mutating it. Viral infection is one of the common environmental factors for complex diseases. For example, the human immunodeficiency virus (HIV) infection can cause acquired immune deficiency syndrome (AIDS), HBV, and HCV infections are associated with hepatocellular carcinoma, and human papillomavirus infection is a causal factor in cervical carcinoma. In this study, to investigate how HIV infection affects DNA methylation, we analyzed the blood DNA methylation data of 485 512 sites in 44 HIV- and 142 HIV + patients. Several advanced computational methods were applied to identify the core distinctive features that were different between the HIV patients and the healthy controls. These methods can be used for differentiating HIV-infected patients from uninfected ones. These core distinctive DNA methylation features were confirmed to be functionally connected to premature aging and abnormal immune regulation, two typical pathological symptoms of HIV infection, revealing the potential regulatory mechanisms of HIV infection on the DNA methylation status of the host cells and provided novel insights on the pathogenesis of HIV infection and AIDS.
许多复杂疾病或特征是遗传和环境因素共同作用的结果。环境因素通过改变表观遗传学来影响人体，而表观遗传学可以控制基因组的活性而不使其发生突变。病毒感染是复杂疾病的常见环境因素之一。例如，人类免疫缺陷病毒（HIV）感染可导致获得性免疫缺陷综合征（AIDS），HBV 和 HCV 感染与肝细胞癌有关，人乳头瘤病毒感染是宫颈癌的一个致病因素。在这项研究中，为了研究 HIV 感染如何影响 DNA 甲基化，我们分析了 44 名 HIV 感染者和 142 名 HIV 阳性患者的血液 DNA 甲基化数据，共 485512 个位点。应用了几种先进的计算方法来识别 HIV 感染者和健康对照之间存在差异的核心特征。这些方法可用于区分 HIV 感染者和未感染者。这些核心的独特 DNA 甲基化特征被证实与过早衰老和异常免疫调节功能相关，这是 HIV 感染的两个典型病理症状，揭示了 HIV 感染对宿主细胞 DNA 甲基化状态的潜在调控机制，并为 HIV 感染和艾滋病的发病机制提供了新的见解。
