Articles producció científica> Ciències Mèdiques Bàsiques

Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control

  • Identification data

    Identifier: imarina:9262250
    Authors:
    Masip JRallón NYeregui EOlona MResino SBenito JMViladés CGarcía-Pardo GAlcamí JRuiz-Mateos EGómez-Bertomeu FVargas MNavarro MOteo JAPineda JAMartí AAlba VVidal FPeraire JRull A
    Abstract:
    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.
  • Others:

    Author, as appears in the article.: Masip J; Rallón N; Yeregui E; Olona M; Resino S; Benito JM; Viladés C; García-Pardo G; Alcamí J; Ruiz-Mateos E; Gómez-Bertomeu F; Vargas M; Navarro M; Oteo JA; Pineda JA; Martí A; Alba V; Vidal F; Peraire J; Rull A
    Department: Ciències Mèdiques Bàsiques
    URV's Author/s: Garcia Pardo, Graciano / Gomez Bertomeu, Frederic-Francesc / Martí Zaragoza, Àlex / Masip Morcillo, Jenifer / Olona Cabases, Maria Montserrat / Peraire Forner, José Joaquin / RULL AIXA, ANNA / Vidal Marsal, Francisco / Vilades Laborda, Consuelo Gloria / Yeregui Etxeberria, Elena
    Keywords: Viral Metabolomics Mass spectrometry Long-term Lipidomics Kreb's cycle Hiv infection Elite controllers (ecs) Elite controllers viral profiles nonprogressors mass spectrometry long-term lipidomics kreb's cycle hiv infection glucose elite controllers (ecs) cycle activation absence
    Abstract: 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.
    Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Odontología Nutrição Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Immunology and allergy Immunology Farmacia Engenharias iii Engenharias ii Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciência de alimentos Biotecnología Biodiversidade
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: graciano.garcia@urv.cat frederic-francesc.gomez@urv.cat joaquim.peraire@urv.cat consuelo.vilades@urv.cat elena.yeregui@estudiants.urv.cat alex.marti@estudiants.urv.cat jenifer.masip@estudiants.urv.cat jenifer.masip@estudiants.urv.cat francesc.vidal@urv.cat
    Author identifier: 0000-0002-8039-2889 0000-0001-7808-5479 0000-0002-2991-9593 0000-0002-6692-6186
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.frontiersin.org/articles/10.3389/fimmu.2022.822272/full
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Frontiers In Immunology. 13 822272-
    APA: Masip J; Rallón N; Yeregui E; Olona M; Resino S; Benito JM; Viladés C; García-Pardo G; Alcamí J; Ruiz-Mateos E; Gómez-Bertomeu F; Vargas M; Navarro M; (2022). Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control. Frontiers In Immunology, 13(), 822272-. DOI: 10.3389/fimmu.2022.822272
    Article's DOI: 10.3389/fimmu.2022.822272
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2022
    Publication Type: Journal Publications
  • Keywords:

    Immunology,Immunology and Allergy
    Viral
    Metabolomics
    Mass spectrometry
    Long-term
    Lipidomics
    Kreb's cycle
    Hiv infection
    Elite controllers (ecs)
    Elite controllers
    viral
    profiles
    nonprogressors
    mass spectrometry
    long-term
    lipidomics
    kreb's cycle
    hiv infection
    glucose
    elite controllers (ecs)
    cycle
    activation
    absence
    Zootecnia / recursos pesqueiros
    Saúde coletiva
    Química
    Odontología
    Nutrição
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    Immunology and allergy
    Immunology
    Farmacia
    Engenharias iii
    Engenharias ii
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciência de alimentos
    Biotecnología
    Biodiversidade
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