Comparative DNA Methylation Profiling Reveals an Immunoepigenetic Signature of HIV-related Cognitive Impairment

• Published in: Scientific reports 2016-09, Vol.6 (1), p.33310-33310, Article 33310
• Main Authors: Corley, Michael J., Dye, Christian, D’Antoni, Michelle L., Byron, Mary Margaret, Yo, Kaahukane Leite-Ah, Lum-Jones, Annette, Nakamoto, Beau, Valcour, Victor, SahBandar, Ivo, Shikuma, Cecilia M., Ndhlovu, Lishomwa C., Maunakea, Alika K.
• Format: Article
• Language: English
• Subjects: 38; 45; 45/23; 45/47; 49/31; 49/39; 49/90; 631/208/176/1988; 631/250/2504/342; 631/250/255/1901; 631/378/1689/132; Aged; Central nervous system; Central Nervous System - immunology; Central Nervous System - metabolism; Central Nervous System - pathology; Central Nervous System - virology; Cognitive ability; Cognitive Dysfunction - etiology; Cognitive Dysfunction - genetics; Cognitive Dysfunction - immunology; Cognitive Dysfunction - pathology; CpG islands; Deoxyribonucleic acid; Disc1 protein; DNA; DNA fingerprinting; DNA methylation; DNA Methylation - genetics; Female; Gene expression; Gene Expression Regulation - genetics; Genomes; HIV - genetics; HIV - pathogenicity; HIV Infections - complications; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - pathology; Humanities and Social Sciences; Humans; Macrophages; Male; Measuring techniques; Middle Aged; Monocytes; Monocytes - immunology; Monocytes - pathology; multidisciplinary; Neuropathogenesis; Psychology; Science; Transcriptome - genetics; Viremia
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep33310

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.