Immunometabolism is a key factor for the persistent spontaneous elite control of HIV-1 infection
Por:
Tarancon-Diez L, Rodríguez-Gallego E, Rull A, Peraire J, Viladés C, Portilla I, Jimenez-Leon MR, Alba V, Herrero P, Leal M, Ruiz-Mateos E and Vidal F
Publicada:
1 abr 2019
Ahead of Print:
14 mar 2019
Resumen:
Background: Approximately 25% of elite controllers (ECs) lose their virological control by mechanisms that are only partially known. Recently, immunovirological and proteomic factors have been associated to the loss of spontaneous control. Our aim was to perform a metabolomic approach to identify the underlying mechanistic pathways and potential biomarkers associated with this loss of control.
Methods: Plasma samples from EC who spontaneously lost virological control (Transient Controllers, TC, n = 8), at two and one year before the loss of control, were compared with a control group of EC who persistently maintained virological control during the same follow-up period (Persistent Controllers, PC, n = 8). The determination of metabolites and plasma lipids was performed by GC-qTOF and LC-qTOF using targeted and untargeted approaches. Metabolite levels were associated with the polyfunctionality of HIV-specific CD8(+)T-cell response.
Findings: Our data suggest that, before the loss of control, TCs showed a specific circulating metabolomic profile characterized by aerobic glycolytic metabolism, deregulated mitochondrial function, oxidative stress and increased immunological activation. In addition, CD8(+) T-cell polyfunctionality was strongly associated with metabolite levels. Finally, valine was the main differentiating factor between TCs and PCs.
Interpretation: All these metabolomic differences should be considered not only as potential biomarkers but also as therapeutic targets in HIV infection. (C) 2019 The Authors. Published by Elsevier B.V.
Filiaciones:
Tarancon-Diez L:
Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain
Rodríguez-Gallego E:
Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain
Rull A:
Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain
Peraire J:
Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain
Viladés C:
Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain
Portilla I:
Infectious Diseases, Instituto de Investigación Sanitaria y Biomédica de Alicante, ISABIAL - FISABIO, Hospital General Universitario de Alicante, Alicante, Spain
Jimenez-Leon MR:
Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain
Alba V:
Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain
Herrero P:
Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), Reus, Spain
Leal M:
Servicio de Medicina Interna, Hospital Viamed Santa Ángela de la Cruz, Sevilla, Spain
Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Sevilla
Ruiz-Mateos E:
Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain
Vidal F:
Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain
Open Access
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