Transcriptional analysis of human peripheral CXCR5mem and CXCR5neg HIV-specific CD4 T cells in progressive disease
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PROVIDER: PRJNA527042 | ENA |
REPOSITORIES: ENA
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Project description:The virus-specific CD4+ T cell dysfunction associated with failure to control chronic infections is poorly understood in humans. A striking enrichment of a Tfh signature is observed in ex vivo stimulated HIV-specific CD4 T cells of Chronic progressors (CPs) compared to Elite controls (ECs), which was not due to a higher fraction of CXCR5mem HIV-specific CD4 in CPs. Here, we sought to define the cell subsets that contributed to the TFH transcriptional signature observed in CPs, applying microarray analysis to paired live-sorted subsets of CXCR5mem and CXCR5neg HIV-specific CD4+ T cells from CPs and ECs . The Tfh signature was not confined to TFH but also atypically enriched in CXCR5neg non-TFH cells and increased expression of key TFh molecules were enriched in the CXCR5neg HIV-specific CD4 T cells of CPs compared to ECs. Thus, altered differentiation is central to HIV-specific CD4+ T cell impairment and involves both gain and loss of functions.
2019-07-15 | GSE128280 | GEO
Project description:The virus-specific CD4+ T cell dysfunction associated with failure to control chronic infections is poorly understood in humans. In this study we sought to determine transcriptional signatures that link HIV-specific T cell help to viral control by performing genome wide transcriptional analysis on ex vivo stimulated HIV-specific CD4+ T cells from HIV-infected subjects with diverse viral loads, who were not on antiretroviral therapy at time of sampling.
2019-07-15 | GSE129872 | GEO
Project description:We examined the gene expression profiles in ex vivo human CD4+ and CD8+ T cells from untreated HIV-infected individuals at different clinical stages and rates of disease progression. Profiles of pure CD4+ and CD8+ T cells subsets from HIV-infected nonprogressors who controlled viremia were indistinguishable from HIV-uninfected individuals. Similarly, no gene clusters could distinguish T cells from individuals with early from chronic progressive HIV infection, whereas differences were observed between uninfected or nonprogressors versus early or chronic progressors. In early/chronic HIV infection, three characteristic gene expression signatures were observed: (1) CD4+ and CD8+ T cells showed increased expression of interferon stimulated genes (ISGs). However, some ISGs including CXCL9, CXCL10, and CXCL11, and the IL15R? in both CD4+ and CD8+ T cells and the anti-HIV ISG APOBEC3G in CD4+ T cells, were not upregulated. (2) CD4+ and CD8+ T cells showed a cluster similar to that observed in thymocytes, and (3) more genes were differentially regulated in CD8+ T cells than in CD4+ T cells, including a cluster of genes downregulated exclusively in CD8+ T cells. In conclusion, HIV infection induces a persistent T cell transcriptional profile, early in infection, characterized by a dramatic but potentially aberrant interferon response, and a profile suggesting an active thymic output. We studied a cohort of HIV infected individuals with various clinical stages of HIV infection and healthy uninfected volunteers as a control group (Table 1). We included 5 individuals with early HIV infection (A), five with chronic progressive HIV infection (C), five individuals with non-progressive HIV infection with low or undetectable viral loads (L) and five HIV uninfected individuals (N). The HIV infected individuals were never on therapy prior to entering the study. Samples were taken once from each donor.
2007-11-11 | E-GEOD-6740 | biostudies-arrayexpress
Project description:Transcriptional analysis of HIV-specific CD4+ T cells in progressive disease and in spontaneously controlled infection.
| PRJNA533078 | ENA
Project description:Analysis of global gene expression profiles of flow cytometry-sorted, different pathogen-specific CD4+ T cell populations from the same peripheral blood mononuclear cells (PBMC), to identify molecular parameters that regulate differential susceptibilities of these CD4+ T cells to HIV infection. The results reveal distinct gene expression profiles between CMV-specific and tetanus toxoid/Candida-specific CD4+ T cells that involved selective upregulation of comprehensive innate antiviral
2012-12-13 | GSE42853 | GEO
Project description:Analysis of global gene expression profiles of flow cytometry-sorted, different pathogen-specific CD4+ T cell populations from the same peripheral blood mononuclear cells (PBMC), to identify molecular parameters that regulate differential susceptibilities of these CD4+ T cells to HIV infection. The results reveal distinct gene expression profiles between CMV-specific and tetanus toxoid/Candida-specific CD4+ T cells that involved selective upregulation of comprehensive innate antiviral Total RNA extracted from CFSE-low, flow-sorted pathogen-specific CD4+ T cells were analyzed for global gene expression. Changes in gene expression were compared between CMV to combined TT/Candida, or TT/CMV and Candida/CMV.
2012-12-13 | E-GEOD-42853 | biostudies-arrayexpress
Project description:Human Immunodeficiency Virus type-1 (HIV-1)-infected individuals show metabolic alterations of CD4 T cells through unclear mechanisms with undefined consequences. We analyzed the transcriptome of CD4 T cells from HIV-1 patients and revealed that elevated oxidative phosphorylation (OXPHOS) pathway is associated with poor outcomes. Inhibition of OXPHOS by the FDA-approved drug metformin, which targets mitochondrial respiratory chain complex I, suppresses HIV-1 replication in human CD4 T cells and humanized mice. In patients, HIV-1 peak viremia positively correlates with the expression of NLRX1, a mitochondrial innate immune receptor. Quantitative proteomics and metabolic analyses reveal that NLRX1 enhances OXPHOS and glycolysis during HIV-1-infection of CD4 T cells to promote viral replication. At the mechanistic level, HIV infection induces the association of NLRX1 with the mitochondrial protein, FASTKD5, to promote the expression of mitochondrial respiratory complex components. This study uncovers the OXPHOS pathway in CD4 T cells as a target for HIV-1 therapy.
2022-02-16 | PXD023565 | Pride
Project description:Host directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Since HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo. A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1 infected patients with paired samples on and off antiretroviral treatment. In the in vitro experiment, the proteome of CD4+ T cells was quantified over a time course following HIV-1 infection. 1,725 host cell proteins and 4 HIV-1 proteins were quantified, with 145 proteins changing significantly during the time course. Changes in the proteome peaked 24 hours after infection, concomitantly with significant HIV-1 protein production. In the in vivo branch of the study, CD4+ T cells from viremic patients and those with no detectable viral load after treatment were sorted and the proteomes quantified. We consistently detected 895 proteins, 172 of which were considered to be significantly different between viraemic patients and patients undergoing successful treatment. The proteome of in vitro infected CD4+ T cells was modulated on multiple functional levels, including TLR-4 signalling and the type 1 interferon signalling pathway. Perturbations in the type 1 interferon signalling pathway were recapitulated in CD4+ T cells from patients. The study shows that proteome maps generated by SWATH-MS indicate a range of functionally significant changes in the proteome of HIV infected human CD4+ T cells. Exploring these perturbations in more detail may help identify new targets for immune based interventions.
2017-02-28 | PXD005234 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE14278: Comparison of CD4+ T cell function between HIV-1 resistant and HIV-1 susceptible individuals (Affymetrix) GSE14279: Comparison of CD4+ T cell function between HIV-1 resistant and HIV-1 susceptible individuals (Immune) Refer to individual Series
2010-05-07 | E-GEOD-14280 | biostudies-arrayexpress
Project description:To systematically examine host-virus interaction in HIV infection, we used isobaric tag-based quantitative mass spectrometry to perform a proteomic profiling of HIV infection of human primary CD4 T cells.
| MSV000082987 | MassIVE