Unknown,Transcriptomics,Genomics,Proteomics

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Methylome-wide analysis of chronic HIV infected patients and healthy controls

ABSTRACT: Current therapy has turned HIV infection into a chronic condition. Clinically, some patients suffer prematurely from ailments associated with advanced age; however, the relationship between HIV and aging is unclear. Here we have collected a large cohort of HAART treated HIV+ subjects with both recent and chronic infection and recapitulated the shared phenotype of HIV and age. To further understand this signal, we applied validated models of DNA methylation-based biological age to establish a clear link between HIV infection and molecular age advancement. We then show this result to be robust to HIV duration, cellular composition, and general methylome disorder. Finally we show a pattern of hypomethylation in HIV+ individuals at the HLA locus. Together these results lead to a much-needed better understanding of the epigenetic consequences and gerontological aspects of chronic HIV infection. To determine whether HIV is associated with signs of aberrant biological aging, samples of whole blood were collected from HIV-infected, HAART-treated but otherwise healthy non-Hispanic white males (no hepatitis C co-infection, no diabetes, and strict adherence to therapy) and healthy non-Hispanic white male controls. DNA was extracted from whole blood and genome-wide methylation profiles of each sample were determined using the Illumina Infinium HumanMethylation450 BeadChip array. As a validation, a second cohort of subjects was profiled by flow-sorting cells and measuring methylation in pure-cell populations. Data were normalized and controlled for quality using standard techniques. Please note that the following samples were excluded from the data processing by quality control steps; METI-6 METI-7 352_CD4 381_CD4 however, their raw data was provided so that the full pipeline could be reproduced.

ORGANISM(S): Homo sapiens

SUBMITTER: Andrew Gross

PROVIDER: E-GEOD-67705 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: Many studies have shown that long noncoding RNAs (lncRNAs) derived from the host and human immunodeficiency virus (HIV) itself play important roles in virus-host interactions and viral pathogenesis. It is unclear whether lncRNAs were involved in ART therapy of HIV/AIDS patients. Methods: Six HIV/acquired immunodeficiency syndrome (AIDS) subjects pre-HAART and post-HAART with effective control of plasma viremia (<20 HIV RNA copies/ml) and 6 healthy subjects were recruited in this study to perform RNA sequencing. The expression profiles of lncRNAs and mRNAs were obtained, to exploration of the potential roles of lncRNAs, trans- and cis-acting analysis was used. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to sort out functional categories of genes. Results: We identified a total of 974 lncRNAs whose expression levels were restored to normal after ART therapy. The results of the cis-acting analysis showed that only six lncRNAs have cis-regulated target genes, among which the target gene RP11-290F5.1, interferon regulatory factors 2 (IRF2), could promote HIV replication. We also identified lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression between pre- and post-HAART, and the differences were significant. We selected lncRNA CTB-119C2.1 for qRT–PCR verification, and the results were consistent with those of RNA-seq. RAB3A and GADD45A, two of the lncRNA CTB-119C2.1-associated genes, have been shown to be associated with HIV infection. KEGG analysis of lncRNA CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway or pathways related to cell circulation and DNA replication. Conclusion: In this study, we used RNA-seq to systematically compare the expression profiles of lncRNAs in HIV subjects between untreated and treated time points. We successfully identified some lncRNAs with differential expression during certain periods (no HIV infection, HIV infection before treatment, and after treatment). Their expression is associated with HIV viral loads, and some of their regulating genes were found to be involved in HIV pathogenesis through bioinformatic analysis. These findings could help to reveal the underlying molecular mechanism of the progression of HIV infection.

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Methylome-wide analysis of chronic HIV infected patients and healthy controls

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