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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Detalhes bibliográficos
Autores: Masip, Jenifer, Rallón, Norma, Yeregui, Elena, Olona, Montserrat, Resino, Salvador, Benito, José Miguel, 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, ECRIS integrated in the Spanish AIDS Research Network
Tipo de documento: artigo
Data de publicação:2022
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositório:Repisalud
Idioma:inglês
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/14870
Acesso em linha:http://hdl.handle.net/20.500.12105/14870
Access Level:Acceso aberto
Palavra-chave:HIV Infections
HIV-1
Follow-Up Studies
Humans
Ketoglutaric Acids
Lipids
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spelling Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV ControlMasip, JeniferRallón, NormaYeregui, ElenaOlona, MontserratResino, SalvadorBenito, José MiguelViladés, ConsueloGarcía-Pardo, GracianoAlcamí, JoséRuiz-Mateos, EzequielGómez-Bertomeu, FredericVargas, MontserratNavarro, MartaOteo, José APineda, Juan AMartí, AnnaAlba, VerónicaVidal, FrancescPeraire, JoaquinRull, AnnaECRIS integrated in the Spanish AIDS Research NetworkHIV InfectionsHIV-1Follow-Up StudiesHumansKetoglutaric AcidsLipidsLong-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 MediaUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)Rovira i Virgili University (España)Instituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas (España)Unión Europea. Fondo Social Europeo (ESF/FSE)Agència de Gestió d´Ajuts Universitaris i de Recerca (AGAUR)Gilead Sciences (Spain)Red de Investigación Cooperativa en Investigación en Sida (España)20222022-08-0520222022-04-2020222022-04-20research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/14870reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/148702026-06-12T12:43:37Z
dc.title.none.fl_str_mv 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
spellingShingle Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control
Masip, Jenifer
HIV Infections
HIV-1
Follow-Up Studies
Humans
Ketoglutaric Acids
Lipids
title_short 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_sort Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control
dc.creator.none.fl_str_mv Masip, Jenifer
Rallón, Norma
Yeregui, Elena
Olona, Montserrat
Resino, Salvador
Benito, José Miguel
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
ECRIS integrated in the Spanish AIDS Research Network
author Masip, Jenifer
author_facet Masip, Jenifer
Rallón, Norma
Yeregui, Elena
Olona, Montserrat
Resino, Salvador
Benito, José Miguel
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
ECRIS integrated in the Spanish AIDS Research Network
author_role author
author2 Rallón, Norma
Yeregui, Elena
Olona, Montserrat
Resino, Salvador
Benito, José Miguel
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
ECRIS integrated in the Spanish AIDS Research Network
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Rovira i Virgili University (España)
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas (España)
Unión Europea. Fondo Social Europeo (ESF/FSE)
Agència de Gestió d´Ajuts Universitaris i de Recerca (AGAUR)
Gilead Sciences (Spain)
Red de Investigación Cooperativa en Investigación en Sida (España)
dc.subject.none.fl_str_mv HIV Infections
HIV-1
Follow-Up Studies
Humans
Ketoglutaric Acids
Lipids
topic HIV Infections
HIV-1
Follow-Up Studies
Humans
Ketoglutaric Acids
Lipids
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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-08-05
2022
2022-04-20
2022
2022-04-20
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/14870
url http://hdl.handle.net/20.500.12105/14870
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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