title: Comparative DNA Methylation Profiling Reveals an Immunoepigenetic Signature of HIV-related Cognitive Impairment.
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.
authors.affiliation: Department of Native Hawaiian Health, John A. Burns School of Medicine, Suite 1016B, University of Hawaii, Honolulu, HI 96813, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Corley
authors.affiliation: Department of Native Hawaiian Health, John A. Burns School of Medicine, Suite 1016B, University of Hawaii, Honolulu, HI 96813, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Dye
authors.affiliation: Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB325C, Honolulu, HI 96813, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: D'Antoni
authors.affiliation: Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB325C, Honolulu, HI 96813, USA.
authors.forename: Mary Margaret
authors.initials: MM
authors.lastname: Byron
authors.affiliation: Department of Native Hawaiian Health, John A. Burns School of Medicine, Suite 1016B, University of Hawaii, Honolulu, HI 96813, USA.
authors.forename: Kaahukane Leite-Ah
authors.initials: KL
authors.lastname: Yo
authors.affiliation: Department of Native Hawaiian Health, John A. Burns School of Medicine, Suite 1016B, University of Hawaii, Honolulu, HI 96813, USA.
authors.forename: Annette
authors.initials: A
authors.lastname: Lum-Jones
authors.affiliation: Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB, Honolulu, HI 96815, USA.
authors.forename: Beau
authors.initials: B
authors.lastname: Nakamoto
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
authors.affiliation: Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB325C, Honolulu, HI 96813, USA.
authors.forename: Ivo
authors.initials: I
authors.lastname: SahBandar
authors.affiliation: Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB, Honolulu, HI 96815, USA.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shikuma
authors.affiliation: Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB325C, Honolulu, HI 96813, USA.|Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB, Honolulu, HI 96815, USA.
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.affiliation: Department of Native Hawaiian Health, John A. Burns School of Medicine, Suite 1016B, University of Hawaii, Honolulu, HI 96813, USA.
authors.forename: Alika K
authors.initials: AK
authors.lastname: Maunakea
mesh_terms: D000368:Aged; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D060825:Cognitive Dysfunction / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006678:HIV / Q000235:genetics / Q000472:pathogenicity; D015658:HIV Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D059467:Transcriptome / Q000235:genetics