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HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

ABSTRACT: Exploratory microarray analysis identified significant changes in gene expression in adipose tissue. These included changes in genes regulating lipid and steroid metabolic processes and electron carrier activity in HIV-infected patients receiving antiretroviral therapy (ART). Additional genes involved in metabolic processes and mitochondrial function were found to be up-regulated in the adipose tissue of HIV-positive patients compared with HIV-negative controls.

ORGANISM(S): Homo sapiens

PROVIDER: GSE30310 | GEO | 2011/07/07

SECONDARY ACCESSION(S): PRJNA143573

REPOSITORIES: GEO

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HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

Project description:Exploratory microarray analysis identified significant changes in gene expression in adipose tissue. These included changes in genes regulating lipid and steroid metabolic processes and electron carrier activity in HIV-infected patients receiving antiretroviral therapy (ART). Additional genes involved in metabolic processes and mitochondrial function were found to be up-regulated in the adipose tissue of HIV-positive patients compared with HIV-negative controls. To identify differential gene expression in different tissues (PBMC, muscle, adipose tissue) between HIV patient groups (HIV negative, HIV positive with ART, HIV positive without ART).

2011-07-07 | E-GEOD-30310 | biostudies-arrayexpress

Antiretroviral therapy potentiates high-fat diet induced obesity and glucose intolerance

Project description:Background Breakthroughs in HIV treatment, especially antiretroviral therapy (ART), have massively reduced mortality. However, ART-treated individuals display elevated rates of obesity, diabetes, and cardiovascular disease, collectively known as metabolic syndrome. These co-morbidities represent a considerable threat to long-term survival and quality of life. Previous studies have shown that high-fat feeding induces persistent low-grade systemic and adipose tissue inflammation contributing to insulin resistance and metabolic dysregulation via adipose-infiltrating macrophages. Methods and Results Studies herein test the hypothesis that ART potentiates the inflammatory effects of a high-fat diet (HFD). C57Bl/6J mice on a HFD or standard chow containing ART or vehicle, were subjected to functional metabolic testing, RNA-sequencing of epididymal white adipose tissue (eWAT), and array-based kinomic analysis of eWAT-infiltrating macrophages. ART-treated mice on a HFD displayed fat mass accumulation, impaired glucose tolerance, and potentiated insulin resistance. Gene set enrichment and kinomic array analyses revealed a pro-inflammatory transcriptional signature depicting granulocyte migration and activation. Conclusions The current study reveals a HFD-ART interaction that increases inflammatory transcriptional pathways in eWAT consistent with macrophage infiltration, resulting in impaired glucose metabolism, energy balance, and metabolic dysfunction.

2018-09-14 | GSE110035 | GEO

Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns.

Project description:Background. Previous epigenome-wide association studies have shown that HIV infection can disrupt the host DNA methylation landscape. However, it remains unclear how antiretroviral therapy (ART) affects the HIV-induced epigenetic modifications. Methods. 184 individuals with HIV from the NEAT001/ANRS143 clinical trial (with pre-ART and post-ART samples [96 weeks of follow-up]) and 44 age-and-sex matched individuals without HIV were included. We compared genome-wide DNA methylation profiles in whole blood between groups adjusting for age, sex, batch effects, and leucocyte type heterogeneity. Findings. We identified 430 differentially methylated positions (DMPs) between HIV+ pre-ART individuals and HIV-uninfected controls. In participants with HIV, ART initiation modified the DNA methylation levels at 845 CpG positions and restored 49.3% of the changes found between HIV+ pre-ART and HIV-uninfected individuals. We only found 15 DMPs when comparing DNA methylation profiles between HIV+ post-ART individuals and participants without HIV. The Gene Ontology enrichment analysis of DMPs associated with untreated HIV infection revealed an enrichment in biological processes regulating the immune system and antiviral responses. In participants with untreated HIV infection, DNA methylation levels at top HIV-related DMPs were associated with CD4/CD8 ratios and viral loads. Changes in DNA methylation levels after ART initiation were weakly correlated with changes in CD4+ cell counts and the CD4/CD8 ratio. Interpretation. Control of HIV viraemia after 96 weeks of ART initiation restores most of the host DNA methylation changes that occurred before antiretroviral treatment of HIV infection.

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Dominant CD4+ T cell receptors remain stable throughout antiretroviral therapymediated immune restoration in people with HIV

Project description:In people with HIV (PWH), the post antiretroviral therapy (ART) window is critical for immune restoration and HIV reservoir stabilization. We employ deep immune profiling, T cell receptor (TCR) sequencing and examine proliferation to assess how ART impacts T cell homeostasis. Hierarchies and frequencies of dominant CD4 TCR clonotypes (0.1-11% of all CD4+ T cells) remain stable post-ART, suggesting that clonal homeostasis can be independent of homeostatic processes regulating CD4+T cell absolute number, phenotypes and function. The slow restoration of host-immunity post-ART also has implications for the design of ART interruption studies.

2023-10-09 | GSE244867 | GEO

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

Project description:Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed microarray analysis using Affymetrix Arrays in portmortem brain tissues from seven treated and eight untreated HAND patients and six uninfected controls.

2011-09-24 | E-GEOD-28160 | biostudies-arrayexpress

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

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Project description:We compared transcriptional profiles of CD4+ and CD8+ T lymphocytes from HIV infected individuals before and 1 year after interruption of antiretroviral therapy (ART).

2018-01-01 | GSE98902 | GEO

Inflammation and macrophage activation in adipose tissue of HIV-infected patients under antiretroviral treatment.

Project description:We used microarrays to detail the global gene expression profile in subcutaneous adipose tissue between controls and HIV-infected patients under antiretroviral treatment. Subcutaneous adipose tissue biopsy from 7 HIV-infected patients and 6 control subjects were taken for RNA extraction and hybridization on Affymetrix microarrays.

2010-01-09 | E-GEOD-19811 | biostudies-arrayexpress

Transcriptome profiling of cardiomyocytes treated with antiretroviral drugs

Project description:The use of antiretroviral therapy (ART) improved the life expectancy of HIV patients through the suppression of HIV propagation in host. However, recent studies suggest that long-term use of ART induces comorbid conditions and heart failure in surviving HIV patients. The mechanism associated with the antiretroviral drugs (ARVs) induced cardiotoxicity and heart failure is not clear. In this study, we performed an RNA sequencing with ARV drugs-treated neonatal rat ventricular cardiomyocytes to explore drugs-induced cardiotoxicity. RNA-sequencing data analysis identified 1756 differentially expressed genes (padj<0.05) in cardiomyocytes. Out of 1756 genes, 701 genes were upregulated, and 1055 genes were downregulated in drug-treated cardiomyocytes. Functional enrichment analysis of differentially expressed genes was performed using clusterProfiler R and ingenuity pathway analysis. Our study showed that upregulated genes were linked with the biological processes associated with apoptosis, cellular movement or locomotion, cellular stress, and immune response. In contrast, down-regulated genes were involved in cell division and metabolism. Interestingly, we also found that ARV drugs treatment significantly upregulates the expression of a set of genes involved in cardiac enlargement and hypertrophy in the heart. Collectively, ARVs treatment in cardiomyocytes induces cardiotoxicity through differentially regulation of pathological genes expression in cardiomyocytes.

2021-12-29 | GSE188210 | GEO

Profiling of proteome changes in plasma of HIV-infected patients receiving antiretroviral therapy

Project description:Antiretroviral therapy (ART) prevents HIV-1 onward transmission and disease progression, leading to excellent prognosis people living with HIV-1 (PWH). However, significant side effects, complications and impaired immune reconstitution still persist along with ART. We aimed to profile proteome changes in plasma before and after ART to identify the molecular pathways altered by ART and finding potential targets to improve the health of PWH.

2022-03-08 | PXD045070 |

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