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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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