E-MEXP-1586
Ontology highlight
ABSTRACT:
PROVIDER: E-MEXP-1586 | ExpressionAtlas | 2025-01-22
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-MEXP-1586-analysis-methods.tsv | Tabular | |||
| E-MEXP-1586-atlasExperimentSummary.Rdata | Rdata | |||
| E-MEXP-1586-configuration.xml | Xml | |||
| E-MEXP-1586-percentile-ranks.tsv | Tabular | |||
| E-MEXP-1586-zoomifications-log.tsv | Tabular |
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Similar Datasets
Project description:HIV integration in latent and active human CD4-positive t-cells
| PRJNA213846 | ENA
Project description:To identify candidate mechanisms that may confer CTL resistance to HIV reservoir harboring cells, we studied differential intrinsic sensitivity to CTL killing in primary CD4+ T-cells. Human CD4+ T cells were divided into either a “real” condition, where half of the cells were labeled with CFSE and pulsed with the HIV-Env peptide RLRDLLLIVTR (RR11), while the other half received no peptide and were labeled with CTFR, or a “mock” condition where cells were similarly labeled but received no peptide. Both conditions were then co-cultured with the corresponding HIV-specific CTL clone. Our result showed that the comparison between the ‘real survivors’ to the ‘real bystanders’ identified 1,061 differentially expressed genes (DEGs) by setting a threshold as FDR<0.05: 743 upregulated and 318 downregulated. Among these genes, we observed expression profiles that were consistent with specific selection of over-expression of BCL2, and under-expression of caspase-2 and PARP in the ‘real survivor’ cells that resisted elimination by CTL.
2021-01-01 | GSE143879 | GEO
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:Although HIV-1 can directly infect resting CD4+ T cells, virus replication in resting CD4+T cells is very inefficient owing to the different host restriction factors blocking viral replication. The accessory protein Vpx from the major simian immunodeficiency virus (SIV) of rhesus macaque (mac) and HIV-2 lineage could degrade a host restriction factor, SAM and HD domain containing protein 1 (SAMHD1), to facilitate HIV reverse transcription. Interestingly, Vpx proteins from a second SIV lineage, the SIV of redcapped mangabeys or mandrills (SIVrcm/nmd-2), had no effect on SAMHD1 and did not affect the dNTP pool, but strongly increased HIV-1 infection in resting CD4+ T cells although not in primary macrophages. This indicates that Vpx, in addition to SAMHD1,can overcome a previously unexplored restriction factor for lentiviruses. Here to identify this potential restriction factor, we examined Vpxrcm-interacting cellular proteins and found that keratin 72 (KRT72), an intermediate filament protein that is exclusively expressed in resting CD4+ T cells, is a new host antiviral factor targeted by Vpx. Other than Vpx from SIV mac and HIV-2, the Vpxrcm/nmd-2 lineage, which had no effect on the SAMHD1 protein, could strongly promote the degradation of KRT72, resulting in enhanced HIV-1 infection in resting CD4+ T cells. Furthermore, we discovered that KRT72 restricts HIV-1 replication by sequestering incoming HIV-1 capsids in cytoplasmic intermediate filaments (IFs). In the presence of KRT72, HIV-1 capsid cores become attached to the IF and their trafficking toward the nucleus is inhibited. In contrast, in the absence of KRT72, HIV-1 capsids are transported into the nucleus,leading to high levels of integrated HIV-1 DNA. In addition, KRT72 expression was substantially higher in resting CD4+ T cells than in activated CD4+ T cells, and it was rapidly reduced by T cell activation. Collectively, the results show that KRT72 is a new Vpx-counteracted host antiviral factor that acts to tether incoming capsids to the cytoplasmic IF, thereby restricting HIV-1 infection in resting CD4+ T cells.
2025-03-28 | PXD059264 | Pride
Project description:Clonal expansion of HIV infected CD4+ T cells is a barrier to HIV eradication. We previously described a marked reduction in the frequency of the most clonally expanded infected CD4+ T cells in an individual with elite control (ES24) after initiating chemoradiation for metastatic lung cancer with a regimen that included paclitaxel and carboplatin. We tested the hypothesis that this phenomenon was due to a higher susceptibility to the chemotherapeutic drugs of CD4+ T cell clones that were sustained by active proliferation. We studied a CD4+ T cell clone with replication-competent provirus integrated into the ZNF721/ABCA11P genes, termed ZNF721i. We stimulated the clone with its cognate peptide and then exposed the cells to paclitaxel and/or carboplatin or the antiproliferative drug, mycophenolate mofetil. While treatment of cells with the cognate peptide alone led to a marked expansion of the ZNF721i clone, treatment with the cognate peptide followed by culture with either paclitaxel or mycophenolate mofetil abrogated this process. The drugs did not affect the proliferation of other CD4+ T cell clones that were not specific for the cognate peptide. This strategy of antigen-specific stimulation followed by treatment with an antiproliferative agent may lead to the selective elimination of clonally expanded HIV-infected cells.
2025-08-25 | GSE305896 | GEO
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:Cell activation is a vital step for T cell memory/effector differentiation as well as for productive HIV infection. To identify novel regulators of this process, we used next generation sequencing to profile changes in microRNA expression occurring in purified human naive CD4 T cells in response to TCR stimulation and HIV infection. HIV infection had no significant impact on global miR expression in quiescent nave CD4 T cells. We identified miR-34c-5p as a novel miR strongly induced by TCR stimulation of nave CD4 T cells, and found that it was consistently down-regulated in response to viral infection. Over-expression of miR-34c-5p had a positive effect on HIV-1 replication. Finally, we demonstrated that miR-34c-5p alters the expression of several genes involved in TCR signaling and cell activation, identifying it as a novel regulator of nave CD4 T cell activation potentially targeted by HIV infection.
2016-12-21 | E-MTAB-4214 | biostudies-arrayexpress
Project description:Despite extensive efforts, significant gaps remain in our understanding of which host factors promote or restrict human immunodeficiency virus (HIV) infection in human CD4+ T cells. Here, we employed orthogonal genome-wide CRISPR activation (CRISPRa) and CRISPR knockout (CRISPRn) screens in primary CD4+ T cells to discover both pro- and anti-HIV host factors systematically. We used secondary pooled screens and targeted individual CRISPR perturbations to validate high-confidence hits and reveal their diverse mechanisms of action. CRISPRa notably revealed potent antiviral factors, including PI16, PPID, SHISA3, and ITM2A – many of which would have been missed by gene knockout experiments alone. When PI16 is overexpressed in CD4+ T cells, it physically interacts with CD4 and numerous HIV host factors involved in viral fusion, and efficiently inhibits HIV entry. We also discovered another novel antiviral factor, PPID (Cyp40). PPID is a paralog of CypA (or PPIA), which is a proviral factor that regulates nuclear entry kinetics of HIV cores. PPID also binds to HIV capsid, but unlike CypA, it restricts infection by blocking nuclear import of the viral core. Structural modeling, evolutionary analyses, and targeted mutagenesis identified domains and residues that mediate restriction of HIV by PPID, including specific substitutions from non-human primate orthologs that improve HIV restriction. Together, our data systematically define the functional HIV-host interaction landscape in primary human T cells and reveal new mechanisms to modulate infection.
2026-04-27 | PXD071892 | Pride
Project description:Sustained Ca2+ entry into CD4+CD8+ double-positive thymocytes is required for positive selection. We identified a voltage-gated Na+ channel (VGSC), essential for positive selection of CD4+ T cells. Pharmacological inhibition of VGSC activity inhibited sustained Ca2+ influx induced by positive-selecting ligands and in vitro positive selection of CD4+ but not CD8+ T cells. In vivo shRNA knockdown of Scn5a specifically inhibited positive selection of CD4+ T cells. Ectopic expression of VGSC in peripheral AND CD4+ T cells bestowed the ability to respond to a positively selecting ligand, directly demonstrating VGSC expression was responsible for increased sensitivity. Thus active VGSCs in thymocytes provides a mechanism by which a weak positive selecting signal can induce sustained Ca2+ signals required for CD4+ T cell development. Pre-selected AND DP thymocytes were stimulated with plate bound peptide-loaded I-Ek Ig dimers. Genes were differentially regulated by positive and negative selection signals. The goal of this study is to identify ion-channel related genes critical for thymic positive selection, given the sustained Ca2+ entry into double positive thymocytes is required for positive selection. Total RNA of pre-selected AND thymocytes stimulated with I-Ek Ig dimers loaded with the positively-selecting peptide gp250, the negatively-selecting agonist peptide MCC, or the non-selecting control peptide Hb were used for the transcriptional profiling analysis. We found 28 genes were differentially down-regulated by MCC stimulation but upregulated by gp250 stimulation. One of them, scn4b, was ion-channel related.
2012-06-30 | E-GEOD-38909 | biostudies-arrayexpress
Project description:Wodarz2007 - HIV/CD4 T-cell interaction
A deterministic model illustrating how
CD4 T-cells can influence HIV infection.
This model is described in the article:
Infection dynamics in
HIV-specific CD4 T cells: does a CD4 T cell boost benefit the
host or the virus?
Wodarz D, Hamer DH.
Math Biosci 2007 Sep; 209(1):
14-29
Abstract:
Recent experimental data have shown that HIV-specific CD4 T
cells provide a very important target for HIV replication. We
use mathematical models to explore the effect of specific CD4 T
cell infection on the dynamics of virus spread and immune
responses. Infected CD4 T cells can provide antigen for their
own stimulation. We show that such autocatalytic cell division
can significantly enhance virus spread, and can also provide an
additional reservoir for virus persistence during anti-viral
drug therapy. In addition, the initial number of HIV-specific
CD4 T cells is an important determinant of acute infection
dynamics. A high initial number of HIV-specific CD4 T cells can
lead to a sudden and fast drop of the population of
HIV-specific CD4 T cells which results quickly in their
extinction. On the other hand, a low initial number of
HIV-specific CD4 T cells can lead to a prolonged persistence of
HIV-specific CD4 T cell help at higher levels. The model
suggests that boosting the population of HIV-specific CD4 T
cells can increase the amount of virus-induced immune
impairment, lead to less efficient anti-viral effector
responses, and thus speed up disease progression, especially if
effector responses such as CTL have not been sufficiently
boosted at the same time.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000663.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000663 | BioModels