Comparative DNA Methylation Profiling Reveals an Immunoepigenetic Signature of HIV-related Cognitive Impairment.
Comparative DNA Methylation Profiling Reveals an Immunoepigenetic Signature of HIV-related Cognitive Impairment.
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DOI：
10.1038/srep33310
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发表时间：
2016-09-15
影响因子：
4.6
通讯作者：
Maunakea AK
中科院分区：
文献类型：
--
作者：
Corley MJ;Dye C;D'Antoni ML;Byron MM;Yo KL;Lum-Jones A;Nakamoto B;Valcour V;SahBandar I;Shikuma CM;Ndhlovu LC;Maunakea AK
单核细胞/巨噬细胞有助于HIV相关的认知障碍（CI）的神经发病机制;然而，在我们对驱动这种关系的确切机制的理解方面仍然存在相当大的差距。此外，与HIV相关CI相关的独特生物学特征是否存在于免疫细胞群中仍然未知。在这里，我们使用全基因组DNA甲基化和基因表达谱分析了来自有和没有CI的HIV感染个体的单核细胞的DNA甲基化组和转录组。我们在单核细胞中鉴定了1，032个CI相关的差异甲基化位点。这些位点与中枢神经系统（CNS）相关的基因网络以及与HIV的相互作用有关。CI组中大部分（70.6%）的基因座表现出较高的DNA甲基化状态，并优先分布在基因组的基因体和基因间区域。CI相关的DNA甲基化状态在12个CpG位点与神经心理学测试成绩相关。CI相关的DNA甲基化也与基因表达差异相关，包括CNS基因CSRNP 1（P = 0.017）、DISC 1（P = 0.012）和NR 4A 2（P = 0.005）;以及已知与HIV病毒血症相关的基因THBS 1（P = 0.003）。这一发现队列数据揭示了与HIV相关CI相关的细胞类型特异性DNA甲基化模式，并提供了一种免疫表观遗传DNA甲基化“特征”，可能用于证实临床评估，告知致病机制，并揭示针对CI的新治疗靶点。
Monocytes/macrophages contribute to the neuropathogenesis of HIV-related cognitive impairment (CI); however, considerable gaps in our understanding of the precise mechanisms driving this relationship remain. Furthermore, whether a distinct biological profile associated with HIV-related CI resides in immune cell populations remains unknown. Here, we profiled DNA methylomes and transcriptomes of monocytes derived from HIV-infected individuals with and without CI using genome-wide DNA methylation and gene expression profiling. We identified 1,032 CI-associated differentially methylated loci in monocytes. These loci related to gene networks linked to the central nervous system (CNS) and interactions with HIV. Most (70.6%) of these loci exhibited higher DNA methylation states in the CI group and were preferentially distributed over gene bodies and intergenic regions of the genome. CI-associated DNA methylation states at 12 CpG sites associated with neuropsychological testing performance scores. CI-associated DNA methylation also associated with gene expression differences including CNS genes CSRNP1 (P = 0.017), DISC1 (P = 0.012), and NR4A2 (P = 0.005); and a gene known to relate to HIV viremia, THBS1 (P = 0.003). This discovery cohort data unveils cell type-specific DNA methylation patterns related to HIV-associated CI and provide an immunoepigenetic DNA methylation “signature” potentially useful for corroborating clinical assessments, informing pathogenic mechanisms, and revealing new therapeutic targets against CI.
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DOI：
10.1093/infdis/jiv277
发表时间：
2015-11-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Horvath S;Levine AJ
通讯作者：
Levine AJ
影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
3.8
作者：
Dedeurwaerder, Sarah;Defrance, Matthieu;Fuks, Francois
通讯作者：
Fuks, Francois
影响因子：
9.9
作者：
Childs, EA;Lyles, RH;McArthur, JC
通讯作者：
McArthur, JC
影响因子：
5.3
作者：
Faissner, Simon;Ambrosius, Bjoern;Chan, Andrew
通讯作者：
Chan, Andrew