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Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control
Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidom...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065415/ https://www.ncbi.nlm.nih.gov/pubmed/35514981 http://dx.doi.org/10.3389/fimmu.2022.822272 |
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author | Masip, Jenifer Rallón, Norma Yeregui, Elena Olona, Montserrat Resino, Salvador Benito, José M. Viladés, Consuelo García-Pardo, Graciano Alcamí, José Ruiz-Mateos, Ezequiel Gómez-Bertomeu, Frederic Vargas, Montserrat Navarro, Marta Oteo, José A. Pineda, Juan A. Martí, Anna Alba, Verónica Vidal, Francesc Peraire, Joaquin Rull, Anna |
author_facet | Masip, Jenifer Rallón, Norma Yeregui, Elena Olona, Montserrat Resino, Salvador Benito, José M. Viladés, Consuelo García-Pardo, Graciano Alcamí, José Ruiz-Mateos, Ezequiel Gómez-Bertomeu, Frederic Vargas, Montserrat Navarro, Marta Oteo, José A. Pineda, Juan A. Martí, Anna Alba, Verónica Vidal, Francesc Peraire, Joaquin Rull, Anna |
author_sort | Masip, Jenifer |
collection | PubMed |
description | Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography–electrospray ionization–quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients). Long-term viral and immunological HIV-1 control was found to be strongly associated with elevated tricarboxylic acid (TCA) cycle function. Interestingly, of the nine metabolites identified in the TCA cycle, α-ketoglutaric acid (p = 0.004), a metabolite implicated in the activation of the mTOR complex, a modulator of HIV latency and regulator of several biological processes, was found to be a key metabolite in the persistent control. On the other hand, a lipidomics panel combining 45 lipid species showed an optimal percentage of separation and an ability to differentiate LTEC-extreme from LTEC-losing, revealing that an elevated lipidomics plasma profile could be a predictive factor for the reignition of viral replication in LTEC individuals. |
format | Online Article Text |
id | pubmed-9065415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90654152022-05-04 Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control Masip, Jenifer Rallón, Norma Yeregui, Elena Olona, Montserrat Resino, Salvador Benito, José M. Viladés, Consuelo García-Pardo, Graciano Alcamí, José Ruiz-Mateos, Ezequiel Gómez-Bertomeu, Frederic Vargas, Montserrat Navarro, Marta Oteo, José A. Pineda, Juan A. Martí, Anna Alba, Verónica Vidal, Francesc Peraire, Joaquin Rull, Anna Front Immunol Immunology Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography–electrospray ionization–quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients). Long-term viral and immunological HIV-1 control was found to be strongly associated with elevated tricarboxylic acid (TCA) cycle function. Interestingly, of the nine metabolites identified in the TCA cycle, α-ketoglutaric acid (p = 0.004), a metabolite implicated in the activation of the mTOR complex, a modulator of HIV latency and regulator of several biological processes, was found to be a key metabolite in the persistent control. On the other hand, a lipidomics panel combining 45 lipid species showed an optimal percentage of separation and an ability to differentiate LTEC-extreme from LTEC-losing, revealing that an elevated lipidomics plasma profile could be a predictive factor for the reignition of viral replication in LTEC individuals. Frontiers Media S.A. 2022-04-20 /pmc/articles/PMC9065415/ /pubmed/35514981 http://dx.doi.org/10.3389/fimmu.2022.822272 Text en Copyright © 2022 Masip, Rallón, Yeregui, Olona, Resino, Benito, Viladés, García-Pardo, Alcamí, Ruiz-Mateos, Gómez-Bertomeu, Vargas, Navarro, Oteo, Pineda, Martí, Alba, Vidal, Peraire and Rull https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Masip, Jenifer Rallón, Norma Yeregui, Elena Olona, Montserrat Resino, Salvador Benito, José M. Viladés, Consuelo García-Pardo, Graciano Alcamí, José Ruiz-Mateos, Ezequiel Gómez-Bertomeu, Frederic Vargas, Montserrat Navarro, Marta Oteo, José A. Pineda, Juan A. Martí, Anna Alba, Verónica Vidal, Francesc Peraire, Joaquin Rull, Anna Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control |
title | Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control |
title_full | Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control |
title_fullStr | Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control |
title_full_unstemmed | Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control |
title_short | Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control |
title_sort | elevated α-ketoglutaric acid concentrations and a lipid-balanced signature are the key factors in long-term hiv control |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065415/ https://www.ncbi.nlm.nih.gov/pubmed/35514981 http://dx.doi.org/10.3389/fimmu.2022.822272 |
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