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Transcriptome analysis of primary monocytes from HIV+ patients with differential responses to therapy

ABSTRACT: This study aimed at investigating the monocytic transcriptome distinction between patients with sustained virus suppression (BDL) and patients with virological failure during highly active antiretroviral therapy (HAART). This study provides the first transcriptomic distinctions in monocytes between viremic patients and BDLs on HAART. Our results reflected the outcome balanced between subversion of monocyte transcriptome by HIV and compensatory effect adapted by host cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52900 | GEO | 2013/12/30

SECONDARY ACCESSION(S): PRJNA230417

REPOSITORIES: GEO

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Transcriptome analysis of primary monocytes from HIV+ patients with differential responses to therapy

Project description:This study aimed at investigating the monocytic transcriptome distinction between patients with sustained virus suppression (BDL) and patients with virological failure during highly active antiretroviral therapy (HAART). This study provides the first transcriptomic distinctions in monocytes between viremic patients and BDLs on HAART. Our results reflected the outcome balanced between subversion of monocyte transcriptome by HIV and compensatory effect adapted by host cells. Total RNA obtained from primary monocytes from five HIV+ patients on HAART who sustainably controlled HIV below detection level (BDL), five HIV+ patients on HAART who consecutively experienced viremia and four healthy HIV sero-negative controls were compared against each other.

2013-12-30 | E-GEOD-52900 | biostudies-arrayexpress

Dysregulation of the colonic mucosally-adherent microbiota associates with HIV disease progression.

Project description:HIV is known to severely affect the gastrointestinal immune system, in particular compartments of immunity that regulate gut microbial composition. Furthermore, recent studies in mice have shown that dysregulation of the gut microbiome can contribute to chronic inflammation, which is a hallmark of HIV and is thought to fuel disease progression. We sought to understand whether the gut microbial community differs in HIV-infected subjects, and whether such putative differences are associated with disease progression. We found that dysbiosis in the gut mucosally-adherent bacterial community associates with markers of chronic inflammation and disease progression in HIV-infected subjects, and this dysbiosis remains in many subjects undergiong antiretroviral therapy. We used G3 PhyloChip microarrays (commercially available from Second Genome, Inc.) to profile gut bacteria in rectosigmoid biopsies from 32 subjects: 6 HIV-infected viremic untreated (VU), 18 HIV-infected subjects on highly active antiretroviral therapy (HAART), 1 HIV-infected long-term non-progressor that is untreated (LTNP), and 9 HIV-uninfected subjects (HIV-).

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Transcriptional profiling of CD4 T-cells in HIV-1 infected patients

2011-01-01 | GSE23879 | GEO

Gene expression before HAART initiation predicts HIV-infected individuals at risk of poor CD4+ T cell recovery.

Project description:Analysis of peripheral blood mononuclear cells (PBMCs) taken from 24 HIV-infected male participants before the start of highly active antiretroviral therapy (HAART). Results identify biomarkers for the identification of HIV-infected participants that progress to good versus poor CD4+ T cell recovery after 48 weeks of HAART.

2009-12-03 | GSE19087 | GEO

Transcriptional profiling of CD4 T-cells in HIV-1 infected patients

Project description:HIV-1 elite controllers maintain undetectable levels of viral replication in the absence of antiretroviral therapy, but their underlying immunological and virological characteristics may vary. Here, we used a whole-genome transcriptional profiling approach to characterize gene expression signatures of CD4 T cells from an unselected cohort of elite controllers. In the majority of elite controllers, transcriptional profiles were similar to HAART-treated patients, while being different from HIV-1 negative persons. Yet, a smaller proportion of elite controllers showed an opposite gene expression pattern that was indistinguishable from HIV-1 negative persons, but different from HAART-treated individuals. Elite controllers with this gene expression signature had significantly higher CD4 T cell counts, smaller levels of HIV-1-specific CD8+ T cell responses and tended to have lower residual HIV-1 viremia as determined by ultra-sensitive single-digit PCR, but did not differ from other elite controllers in terms of HLA class I alleles, age or sex. Thus, these data identify a specific subgroup of elite controllers whose clinical, immunological and gene expression characteristics approximate those of HIV-1 negative persons. PBMC from study persons were stained with monoclonal antibodies against CD3, CD4 and HLA-DR, and subsequently subjected to live sorting at 70 psi using an ARIA cell sorting device (Becton Dickinson) located in a specifically designated biosafety cabinet. Following mRNA extraction form the sorted cells (RNAeasy kit, Qiagen), whole genome transcriptional profiling was performed using WG-DASL microarrays (Illumina) according to standard protocols. We included an unselected cohort of elite controllers (n = 12) and two background populations of HIV-1 negative persons (n = 9) and HIV-1 infected persons effectively treated with HAART (n = 14). Four replicates were included in the study.

2011-01-01 | E-GEOD-23879 | biostudies-arrayexpress

Epigenome analysis in several cohorts of HIV progession and in uninfected individuals

Project description:Genome wide DNA methylation profiling of CD4 T cells from uninfected and HIV-infected individuals (viremic, ART-suppressed and elite controllers [EC]) The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 485,577 CpGs in DNA from peripheral CD4 T cells samples. Samples included: 22 from HIV-uninfected individuals (uninfected group), 42 from HIV-infected individuals (21 from HIV-infected viremic (viremic group) and 21 from the same participants after viral suppression (viral load< 50 copies HIV-1 RNA/plasma) by antiretroviral therapy administrarion (ART group), and 21 from elite controllers (EC group)

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A truncated HIV Tat demonstrates potent and specific latency reversal activity

Project description:The barrier to HIV-1 functional cure is caused by a small pool of latently infected resting CD4 T-cells that persist under antiretroviral therapy. Notably this latent reservoir of infected cells will produce replication-competent infectious virus once prolonged suppressive HAART is withdrawn. The reactivation of HIV-1 gene expression in T-cells harboring latent provirus in HIV-1 patients under HAART will likely result in depletion of this latent reservoir due to cytopathic effects and immune clearance. Many studies have investigated small molecules that reactivate HIV-1 gene expression but to date no latency reversal agent (LRA) has been identified to be specific, non-toxic, and effective in primary T-cells isolated from HIV-1 infected individuals undergoing long-term HAART. Stochastic fluctuations in HIV-1 tat gene expression have been attributed to be essential in the viral progression to latency. We hypothesized that exposing Tat to latently infected CD4 T-cells will result in potent latency reversal. Our results indicate the capacity of an engineered Tat to reactivate HIV-1 in latently infected cells from patients to a similar degree as the protein kinase C agonist PMA (Phorbol 12-Myristate 13-Acetate) while showing no T-cell activation nor any significant transcriptome perturbation in primary CD4 T-cells.

2023-09-05 | GSE235229 | GEO

Cytokine interactome alterations promote oropharyngeal Epstien-barr virus (EBV) replication and shedding during HIV infection

Project description:Proteomic analysis of cytokines in unstimulated oropharyngeal secretions. Epstein-barr virus (EBV) is a type 1 carcinogen which causes many cancers in humans. Here we explored the cytokine involvement of the EBV replication process in the oropharynx. Cytokine interactomic profiles were geneerated to understand the involved signalling pathways in HIV infected group and the healthy group. Proteome profilers were used to understand the major cytokine expression levels that are related to infection and immune regulation. We analyzed unstimulated oropharyngeal samples (UOPS) from 42 healthy subjects and 72 HIV positive subjects using the R & D Proteome Profiler array panels. No techinical replicates were performed. 14 samples in HIV group without therapy (NHAART group); 58 HIV patients with highly active antiretroviral therapy (HAART group); 42 samples in healthy group

2010-04-15 | E-GEOD-21339 | biostudies-arrayexpress

Homo sapiens

Project description:Blastocystis hominis Infection Alters Gut Microbiota in HIV-infected Patients Treated with Highly Active Antiretroviral Therapy (HAART)

| PRJNA788153 | ENA

Obstructive cholestasis compromises balance and alters brain lipid composition in neonatal piglets

Project description:Infants with neonatal cholestasis are prone to neurodevelopmental deficits including neuromotor function. Accumulation of potentially neurotoxic molecules in the bloodstream including ammonia and bile acids and malabsorption of lipids may affect neurodevelopment in these patients. This study examined neuromotor function and bile acid and lipid composition of the brain in a piglet model of obstructive neonatal cholestasis via bile duct ligation (BDL) surgery. Results showed that BDL piglets had compromised balance and increased liver enzyme levels, liver fibrosis and bile duct proliferation compared to SHAM piglets. Plasma and cerebellum bile acid profiles differed between BDL and SHAM piglets with hyocholic acid and conjugated bile acid forms dominating in the BDL group. In the cerebellum there were different lipid profiles, but similar gene expression profiles between the two groups.

2022-06-01 | GSE180600 | GEO

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