Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Profiling whole-tissue metabolic reprogramming during cutaneous poxvirus infection and clearance

ABSTRACT: Background Vaccinia virus (VACV) infection induces prominent changes in host cell metabolism. Little is known about the global metabolic reprogramming that takes place in the whole tissue during viral infection. Here, we performed an unbiased longitudinal metabolomics study in VACV-infected mice to investigate metabolic changes in the tissue during infection. We assessed metabolites in homogenized skin over time in the presence or absence of antigen-specific T cells using untargeted mass spectrometry. VACV infection induced several significant metabolic changes, including in the levels of nucleic acid metabolites (reflecting the impact of viral replication on the skin metabolome). Furthermore, monocyte- and antiviral T cell-produced metabolites, including itaconic acid, glutamine, and glutathione, were significantly increased following infection, highlighting the immune response’s contribution to the global skin metabolome. Additional RNA-Seq of infected skin tissue recapitulated transcriptional changes identified via metabolomics. Overall, our study reveals the metabolic balance of viral replication and the antiviral immune response in the skin and identifies metabolic pathways that could contribute to cutaneous poxvirus control in vivo.

ORGANISM(S): Mus musculus

PROVIDER: GSE236603 | GEO | 2023/11/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Changes in gene expression within the skin caused by antigen-specific memory CD4+ T cells during Vaccinia virus infection.

Project description:To investigate the mechanisms used by memory CD4+ T cells to protect the skin from poxvirus infection, we infected LCMV immune mice with VacV on the right ear skin and VacV expressing the dominant MHC-II restricted epitope from LCMV (VacV-Ii-GP61) on the left ear skin. On day 3 after the co-infection, RNA from whole skin was isolated and gene expression was analyzed using RNA sequencing.

2023-03-24 | GSE227917 | GEO

Global Stable-isotope Tracing Metabolomics Reveals System-wide Metabolic Alternations in Aging Drosophila

Project description:System-wide metabolic homeostasis is crucial for maintaining physiological functions of living organisms. Stable-isotope tracing metabolomics allows to unravel metabolic activity quantitatively by measuring the isotopically labeled metabolites, but has been largely restricted by coverage. Yet, delineating system-wide metabolic homeostasis at the whole-organism level remains non-trivial. Here, we develop a global isotope tracing metabolomics technology to measure labeled metabolites with a metabolome-wide coverage. Using Drosophila as an aging model organism, we probe the in vivo tracing kinetics with quantitative information on labeling patterns, extents and rates on a metabolome-wide scale. We curate a system-wide metabolic network to characterize metabolic homeostasis and disclose a system-wide loss of metabolic coordinations that impacts both intra- and inter-tissue metabolic homeostasis significantly during Drosophila aging. Importantly, we reveal an unappreciated metabolic diversion from glycolysis to serine metabolism and purine metabolism as Drosophila aging. The developed technology facilitates a system-level understanding of metabolic regulation in living organisms.

2022-05-29 | GSE204740 | GEO

Herpesvirus remodel organization and function of mitochondria as infection proceeds

Project description:During the infection, viruses target mitochondria to promote viral replication. Infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteractions of viral factors. The precise structural and functional changes that underlie how mitochondria react to the infection remain largely unclear. Our multimodal integration of advanced imaging, genomics, and metabolomics draws a comprehensive picture of time-dependent changes in mitochondria as HSV-1 infection proceeds from early to late infection.

2024-03-18 | GSE243613 | GEO

Transcriptomic and Metabolomic Analyses Reveal Distinctive Metabolic Characteristics of Superficial and Deep Subcutaneous Adipose Tissues

Project description:Background: The purpose of the study was to find out the molecular and metabolic characteristics of human superficial (SSAT) and deep subcutaneous adipose tissue (DSAT) by performing transcriptomics and metabolomics analysis Methods: We conducted RNA-sequencing and metabolome analysis of SSAT and DSAT in a 48-year-old female patient with a BMI of 27.6 kg/m2. Six samples for each group were collected during a deep inferior epigastric perforator flap breast reconstruction. The calculated transcripts per million values were processed for unsupervised hierarchically clustered heat map generation, and Gene set enrichment analysis. For metabolomics analysis, the samples were analyzed in two modes for cationic and anionic metabolites by Capillary Electrophoresis Time-of-Flight Mass Spectrometry (CE-TOFMS). The metabolome was processed for principal component analysis (PCA) and heat map generation. For indirect metabolic flux analyses, primary adipocytes obtained from SSAT and DSAT were analyzed with Seahorse® extracellular flux analyzer. Results: PCA and heat map data revealed global differences in the transcriptome and metabolome of SSAT and DSAT. The top up-regulated gene sets in the SSAT were related to adipogenesis (FDR q < 0.0001), oxidative phosphorylation (FDR q < 0.0001), fatty acid metabolism (FDR q < 0.0001) and glycolysis (FDR q = 0.001), while inflammatory response (FDR q < 0.05) was the top up-regulated gene set in DSAT. Consequently, the metabolites related to glycolysis were abundant in SSAT, while the metabolites related to fatty acid metabolism and oxidative phosphorylation were abundant in DSAT. In cellular flux analysis, SSAT showed higher level of glycolysis and spare oxidative phosphorylation capacities. Conclusion: The global transcriptome and metabolome difference suggest that human superficial and deep subcutaneous adipose tissue are metabolically distinguishable subcompartments.

2024-10-28 | GSE216803 | GEO

Quantitative temporal proteomic analysis of vaccinia virus infection reveals regulation of histone deacetylases by an interferon antagonist

Project description:Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of IRF-3, NF-κB and type I interferon (IFN) signaling. Here, we used highly multiplexed proteomics to quantify >8,000 cellular proteins and ~80% of viral proteins over seven time points spanning the whole course of VACV infection. This identified multiple novel viral targets, including putative natural killer cell ligands and IFN-stimulated genes. The class II histone deacetylase HDAC5 was selectively degraded early during VACV infection. Use of cell lines in which HDAC5 was overexpressed or knocked out showed that HDAC5 restricted replication of both VACV and herpes simplex virus type 1 (HSV-1). By generating a protein-based temporal classification of VACV gene expression, we identified the early protein C6, a multifunctional IFN antagonist, as the factor that targets HDAC5 for proteasomal degradation. Our approach thus identifies both a novel restriction factor and a viral mechanism of innate immune evasion.

2019-05-07 | PXD012785 | Pride

Distinct metabolic perturbations associated with pediatric Plasmodium falciparum malaria during Intra-erythrocytic development stage

Project description:The goal of this study was to interrogate the impact of metabolic perturbations during P. falciparum infection on the host immune response in a cohort of West African children sampled and profiled before and during infection. Here, we use integrative metabolomics-transcriptomic approach to the investigate potential immunomodulatory effects of serum metabolites during the blood stage of infection.

2021-04-26 | GSE156791 | GEO

Selective modulation of cell surface proteins during vaccinia infection: a resource for identifying viral immune evasion strategies

Project description:The interaction between immune cells and virus-infected targets involves multiple plasma membrane (PM) proteins. A systematic study of PM protein modulation by vaccinia virus (VACV), the paradigm of host regulation, has the potential to reveal not only novel viral immune evasion mechanisms, but also novel factors critical in host immunity. Here, >1000 PM proteins were quantified throughout VACV infection, revealing selective downregulation of known T and NK cell ligands including HLA-C, downregulation of cytokine receptors including IFNAR2, IL-6ST and IL-10RB, and rapid inhibition of expression of certain protocadherins and ephrins, candidate activating immune ligands. Downregulation of most PM proteins occurred via a proteasome-independent mechanism. Upregulated proteins included a decoy receptor for TRAIL. Twenty VACV-encoded PM proteins were identified, of which five were not recognised previously as such. Collectively, this dataset constitutes a valuable resource for future studies on antiviral immunity, host-pathogen interaction, poxvirus biology, vector-based vaccine design and oncolytic therapy.

2022-06-01 | PXD033407 | Pride

B27 inmunopeptidome in vaccinica infected cells

Project description:Identification of natural human leukocyte antigen (HLA) ligandome is a key element to understand the cellular immune responses. Advanced high throughput mass spectrometry analyses identify a relevant, but not complete, fraction of the many tens of thousands of self-peptides generated by the antigen processing in live cells. In infected cells, in addition to this complex HLA ligandome, a minority of peptides from degradation of the few proteins encoded by the viral genome are also bound to HLA class I molecules. In this study, the standard immunoproteomics strategy was modified to include the classical acid stripping treatment after virus infection to enrich the HLA ligandome in virus ligands. Complexes of HLA-B*27:05-bound peptide pools were isolated from vaccinia virus (VACV)-infected cells treated with acid stripping after virus infection. The HLA class I ligandome was identified using high throughput mass spectrometry analyses, yielding 42 and 52 natural peptides processed and presented in untreated and after acid stripping treatment VACV-infected human cells, respectively. Most of these virus ligands were identified in both conditions, but a relevant fraction of VACV ligands detected by mass spectrometry was dependent of acid stripping treatment with almost twice more exclusive viral ligands that the untreated VACV-infected condition. Theoretical binding affinity prediction of the VACV HLA-B*27:05 ligands and acute antiviral T cell response characterization in the HLA transgenic mice model showed no differences between HLA ligands identified under the two conditions: untreated and acid stripping condition. These findings indicated that acid stripping treatment could be useful to identify HLA class I ligands from virus-infected cells.

2021-12-22 | PXD027859 | Pride

One-carbon metabolites control cellular identity [scRNA-seq]

Project description:Metabolomic analyses reveal the specific array of metabolites present in a cell type or tissue at any given time. Multiple lines of evidence indicate that metabolites provide a readout of ongoing cellular functions, and changes in the metabolome correlate with specific biological processes1–4 as seen, for instance, during cellular differentiation. These changes are potentially associated with the regulation of signaling pathways and gene expression networks that are critical to alter cellular identity5–7. However, it is less clear whether specific metabolites or metabolic pathways can drive changes in cellular identity. To identify metabolites engaged with cell state transitions, we performed metabolomic analyses at the earliest stages of cellular differentiation and uncovered metabolites transiently upregulated just as the first transcriptional changes emerged. Specifically, we observed a wave of one-carbon metabolism conserved between three different multipotent stem cell types. Treatment of fully differentiated cells with these metabolites caused the loss of mature identity and transition toward progenitor-like states, thus demonstrating that the metabolome plays a causative role in initiating and modulating cell fate. Our studies reveal a metabolic intervention that can reprogram cellular phenotypes and could potentially be applied in regenerative medicine applications

2024-01-24 | GSE145932 | GEO

One-carbon metabolites control cellular identity [Bulk RNA-seq]

2024-01-24 | GSE145897 | GEO