Project description: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.
Project description:We extracted total RNA from CD4+ T cells from 3 patient groups: chronic HIV-1 patients (CHI), long term non-progressors (LTNPs) and healthy controls (HC). Array results show that a large number of miRNAs are altered in HIV-1 infected patients compared to HC. Most of the differentially expressed miRNAs are down-regulated but there are some up-regulated miRNAs. A particular family of miRNAs which appear to be downregulated in HIV-1 infected patients is the let-7 family of miRNAs.
Project description:We extracted total RNA from CD4+ T cells from 3 patient groups: chronic HIV-1 patients (CHI), long term non-progressors (LTNPs) and healthy controls (HC). Array results show that a large number of miRNAs are altered in HIV-1 infected patients compared to HC. Most of the differentially expressed miRNAs are down-regulated but there are some up-regulated miRNAs. A particular family of miRNAs which appear to be downregulated in HIV-1 infected patients is the let-7 family of miRNAs. In this study, we have included 8 healthy controls, 7 LTNPs and 7 CHI patients. We extracted RNA from magnetically separated CD4+ T cells (separated from peripheral blood mononuclear cells) and ran them on an Agilent miRNA array.
Project description:Opportunistic oral infections are ultimately presented in a vast majority of HIV-infected patients, often causing debilitating lesions that also contribute to deterioration in nutritional health. Although appreciation for the role that the microbiota is likely to play in the initiation and/or enhancement of oral infections has grown considerably in recent years, little is known about the impact of HIV infection on host-microbe interactions within the oral cavity. In the current study, we characterize modulations in the bacterial composition of the lingual microbiome in patients with treated and untreated HIV infection. Bacterial species profiles were elucidated by microarray assay and compared between untreated HIV infected patients, HIV infected patients receiving antiretroviral therapy, and healthy HIV negative controls. The relationship between clinical parameters (viral burden and CD4+ T cell depletion) and the loss or gain of bacterial species was evaluated in each HIV patient group. Characterization of modulations in the dorsal tongue (lingual) microbiota that are associated with chronic HIV infection.
Project description:Although the survival rate for patients infected with human immunodeficiency virus type 1 (HIV-1) has dramatically improved due to recent advancements in antiretroviral therapy, the mechanism of pathogenesis of HIV-associated lipodystrophy remains poorly understood. To elucidate the pathophysiological mechanism of disease, we analyzed gene expression profiles of inguinal adipose tissues from HIV-infected and healthy conrol patients. Genetic analysis revealed that fat tissue from patients with HIV typically had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction including insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis. Of note, triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV.
Project description:There are 19 differentially expressed microRNAs among new HIV-infected cases, old HIV-infected cases and healthy controls. Five microRNAs show trends in healthy controls, new HIV-infected cases and old HIV-infected cases, they are hsa-miR-1291, and hsa-miR-3609 with up-trends, and hsa-miR-3162-3p, hsa-miR-874-5p and hsa-miR-4258 with down-trends.
Project description:Human gut is the primary site for HIV-1 infection. However, most of transcriptomic studies so far were based on peripheral blood (PBMC). The current study compared the transcriptomes of human LPMC between healthy controls and chronically HIV-1 infected patients.