Methylome-wide Analysis of Chronic HIV Infection Reveals Five-Year Increase in Biological Age and Epigenetic Targeting of HLA.

TitleMethylome-wide Analysis of Chronic HIV Infection Reveals Five-Year Increase in Biological Age and Epigenetic Targeting of HLA.
Publication TypeJournal Article
Year of Publication2016
AuthorsGross, AM, Jaeger, PA, Kreisberg, JF, Licon, K, Jepsen, KL, Khosroheidari, M, Morsey, BM, Swindells, S, Shen, H, Ng, CT, Flagg, K, Chen, D, Zhang, K, Fox, HS, Ideker, T
JournalMol Cell
Volume62
Issue2
Pagination157-168
Date Published2016 04 21
ISSN1097-4164
KeywordsAging, Anti-HIV Agents, Case-Control Studies, CD4-CD8 Ratio, CHARTER, Chronic Disease, CpG Islands, Disease Progression, DNA Methylation, Epigenesis, Genetic, External, Gene Expression Profiling, Genome-Wide Association Study, Genotype, HIV Infections, HLA Antigens, Humans, Models, Genetic, Phenotype, Risk Factors, Time Factors, Treatment Outcome
Abstract

HIV-infected individuals are living longer on antiretroviral therapy, but many patients display signs that in some ways resemble premature aging. To investigate and quantify the impact of chronic HIV infection on aging, we report a global analysis of the whole-blood DNA methylomes of 137 HIV+ individuals under sustained therapy along with 44 matched HIV- individuals. First, we develop and validate epigenetic models of aging that are independent of blood cell composition. Using these models, we find that both chronic and recent HIV infection lead to an average aging advancement of 4.9 years, increasing expected mortality risk by 19%. In addition, sustained infection results in global deregulation of the methylome across >80,000 CpGs and specific hypomethylation of the region encoding the human leukocyte antigen locus (HLA). We find that decreased HLA methylation is predictive of lower CD4 / CD8 T cell ratio, linking molecular aging, epigenetic regulation, and disease progression.

DOI10.1016/j.molcel.2016.03.019
Alternate JournalMol. Cell
PubMed ID27105112
PubMed Central IDPMC4995115
Grant ListU24 MH100925 / MH / NIMH NIH HHS / United States
HHSN271201000030C / MH / NIMH NIH HHS / United States
P30 MH062261 / MH / NIMH NIH HHS / United States
P30 CA023100 / CA / NCI NIH HHS / United States
R01 DA030962 / DA / NIDA NIH HHS / United States
T32 GM008666 / GM / NIGMS NIH HHS / United States
P30 GM103509 / GM / NIGMS NIH HHS / United States
U24 CA184427 / CA / NCI NIH HHS / United States