Advertisement

 

 

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.
Author Information (click to view)

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,


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, (click to view)

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,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Scientific reports 2016 09 156() 33310 doi 10.1038/srep33310

Abstract

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.

Submit a Comment

Your email address will not be published. Required fields are marked *

thirteen + 4 =

[ HIDE/SHOW ]