Summary of Study ST002955

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001838. The data can be accessed directly via it's Project DOI: 10.21228/M84H8B This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002955
Study TitleUntargeted metabolomics analysis of plasma from viremic non-progressors (VNP), progressors, and healthy control (HC) patients using high-resolution, high-performance LC-MS/MS analysis.
Study SummaryViremic Non-Progressors (VNPs) maintain normal CD4+ T-cell counts despite uncontrolled HIV-1 replication, but mechanisms leading to CD4+ T-cell preservation are incompletely characterized. We aim to generate a comprehensive understanding of this infrequent phenotype by comparing rates of cellular infection, immunophenotype, genomics, single-cell transcriptomics, metabolomics, and levels of plasma biomarkers in 16 VNPs and 29 HIV+ Progressors. During chronic infection VNPs show lower frequency of HIV-1-infected cells in periphery, which is associated with reduced CCR5 expression and higher prevalence of CCR5Δ32 heterozygosity. The CD8+ T-cell compartment displays a less cytotoxic and less activated phenotype in VNPs. Moreover, despite similar viremia, we found lower bystander CD4+ T-cell death in the VNPs, together with weaker IFN responses, reduced plasma levels of zonulin (a biomarker of intestinal permeability), altered tryptophan catabolism, and preserved LPS responsiveness in vitro. Overall, a complex multifactorial mechanism, suggesting gut-associated lymphoid tissue preservation, underlies resistance to HIV pathogenesis in VNPs.
Institute
IrsiCaixa
Last NameMartinez-Picado
First NameJavier
AddressCarretera de Canyet, s/n, 08916 Badalona, Barcelona
Emailjmpicado@irsicaixa.es
Phone+34 934 65 63 74
Submit Date2023-11-02
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-10-16
Release Version1
Javier Martinez-Picado Javier Martinez-Picado
https://dx.doi.org/10.21228/M84H8B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001838
Project DOI:doi: 10.21228/M84H8B
Project Title:Viremic non-progressors evade HIV-1 pathogenesis by CCR5Δ32 heterozygosity, low activation of cytotoxic cells and reduced IFN response
Project Summary:Viremic Non-Progressors (VNPs) maintain normal CD4+ T-cell counts despite uncontrolled HIV-1 replication, but mechanisms leading to CD4+ T-cell preservation are incompletely characterized. We aim to generate a comprehensive understanding of this infrequent phenotype by comparing rates of cellular infection, immunophenotype, genomics, single-cell transcriptomics, metabolomics, and levels of plasma biomarkers in 16 VNPs and 29 HIV+ Progressors. During chronic infection VNPs show lower frequency of HIV-1-infected cells in periphery, which is associated with reduced CCR5 expression and higher prevalence of CCR5Δ32 heterozygosity. The CD8+ T-cell compartment displays a less cytotoxic and less activated phenotype in VNPs. Moreover, despite similar viremia, we found lower bystander CD4+ T-cell death in the VNPs, together with weaker IFN responses, reduced plasma levels of zonulin (a biomarker of intestinal permeability), altered tryptophan catabolism, and preserved LPS responsiveness in vitro. Overall, a complex multifactorial mechanism, suggesting gut-associated lymphoid tissue preservation, underlies resistance to HIV pathogenesis in VNPs.
Institute:IrsiCaixa
Last Name:Martinez-Picado
First Name:Javier
Address:Carretera de Canyet, s/n, 08916 Badalona, Barcelona
Email:jmpicado@irsicaixa.es
Phone:+34 934 65 63 74

Subject:

Subject ID:SU003068
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Mammals

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Group
SA3218558HC
SA32185620HC
SA32185729HC
SA32185840HC
SA32185938HC
SA32186044HC
SA321901QC-12n/a
SA321902QC-11n/a
SA321903QC-9n/a
SA321904QC-8n/a
SA321905QC-10n/a
SA32186127Progressor
SA32186228Progressor
SA3218631Progressor
SA32186445Progressor
SA32186525Progressor
SA32186622Progressor
SA32186731Progressor
SA32186843Progressor
SA32186939Progressor
SA32187036Progressor
SA32187134Progressor
SA32187242Progressor
SA32187326Progressor
SA3218747Progressor
SA32187510Progressor
SA32187612Progressor
SA3218776Progressor
SA3218785Progressor
SA3218793Progressor
SA3218804Progressor
SA32188114Progressor
SA32188211Progressor
SA32188317Progressor
SA32188419Progressor
SA32188515Progressor
SA32188618VNP
SA32188730VNP
SA32188824VNP
SA32188923VNP
SA3218902VNP
SA32189146VNP
SA32189241VNP
SA32189333VNP
SA3218949VNP
SA32189513VNP
SA32189635VNP
SA32189732VNP
SA32189821VNP
SA32189916VNP
SA32190037VNP
Showing results 1 to 51 of 51

Collection:

Collection ID:CO003061
Collection Summary:Blood samples from HIV+ VNPs and Progressors were collected in EDTA-treated tubes and plasma fraction was isolated by centrifugation at University Hospital Germans Trias i Pujol (Barcelona, Spain). Blood samples from HIV seronegative individuals were collected in EDTA-treated tubes and plasma fraction was isolated by centrifugation at The Wistar Institute (Philadelphia, US).
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR003077
Treatment Summary:No treatment was applied. Inclusion criteria for each group were as follows: HC - HIV seronegative; VNP - viral load > 10,000 copies/ml and CD4 T-cell decay rate < 10% for a minimum of 4 years of ART-free follow-up; Progressor - viral load > 10,000 copies/ml and CD4 T-cell decay rate > 10%.

Sample Preparation:

Sampleprep ID:SP003074
Sampleprep Summary:Briefly, polar metabolites were extracted from 50 µl plasma samples with 500 µl of ice-cold 80:20 (v/v) methanol/water spiked with 1.5 µM heavy-labeled amino acid internal standard mix. Deproteinated supernatants were stored at −80 °C prior to analysis. A quality control (QC) pool sample was made by pooling a small aliquot from each sample extract.
Processing Storage Conditions:-80℃
Extract Storage:-80℃

Chromatography:

Chromatography ID:CH003663
Chromatography Summary:Hydrophilic interaction liquid chromatography (HILIC) was performed at 0.2 ml/min on a ZIC-pHILIC column (2.1 mm × 150 mm, EMD Millipore) at 45 °C. Solvent A was 20 mM ammonium carbonate, 5 µM medronic acid, 0.1% ammonium hydroxide, pH 9.2, and solvent B was acetonitrile. The gradient was 85% B for 2 min, 85% B to 20% B over 15 min, 20% B to 85% B over 0.1 min, and 85% B for 8.9 min. The autosampler was held at 4 °C. For each analysis, 4 µl of sample was injected.
Instrument Name:Thermo Vanquish Horizon UHPLC
Column Name:SeQuant ZIC- pHILIC (150 x 2.1mm,5um)
Column Temperature:45
Flow Gradient:85% B for 2 min, 85% B to 20% B over 15 min, 20% B to 85% B over 0.1 min, and 85% B for 8.9 min
Flow Rate:0.2 ml/min
Solvent A:100% water; 20 mM ammonium carbonate; 5 µM medronic acid; 0.1% ammonium hydroxide, pH 9.2
Solvent B:100% acetonitrile
Chromatography Type:HILIC

Analysis:

Analysis ID:AN004852
Analysis Type:MS
Chromatography ID:CH003663
Num Factors:4
Num Metabolites:190
Rt Units:Minutes
Units:Peak Area
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