Esther Rodríguez-Gallego1, Laura Tarancón-Diez2, Felipe García3, Jorge Del Romero4, Jose Miguel Benito5, Verónica Alba1, Pol Herrero6, Anna Rull1, Beatriz Dominguez-Molina2, Onofre Martinez-Madrid7, Luisa Martin-Pena8,9, Federico Pulido10, Agathe León3, Carmen Rodríguez4, Norma Rallón5, Joaquim Peraire1, Consuelo Viladés1, Manuel Leal2,11, Francesc Vidal1, Ezequiel Ruiz-Mateos2. 1. Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona. 2. Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/Consejo Superior de Investigaciones Científicas/University of Seville, Spain. 3. Hospital Clinic-Fundació Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centre Català d'Investigació i Desenvolupament de Vacunes contra la Sida, Universidad de Barcelona, Spain. 4. Centro Sanitario Sandoval, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain. 5. IIS-Fundación Jiménez Diaz, Universidad Autónoma de Madrid/Madrid Hospital Universitario Rey Juan Carlos, Móstoles, Spain. 6. Centre for Omic Sciences, Unitat Mixta Universitat Rovira i Virgili-Eurecat, Reus, Spain. 7. Unidad Enfermedades Infecciosas, Hospital General Universitario Santa Lucía, Cartagena, Spain. 8. Infectious Disease Service, Son Espases Hospital, Palma de Mallorca, Illes Balears, Spain. 9. Multidisciplinary Group for Infectious Disease Service, Institute of Health Sciences Research, Instituto de Investigación Sanitaria de Palma, Health Research Foundation Ramón Llull, Son Espases Hospital, Palma de Mallorca, Illes Balears. 10. HIV Unit, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain. 11. Servicio de Medicina Interna, Hospital Viamed Santa Ángela de la Cruz, Sevilla, Spain.
Abstract
BACKGROUND: Elite controllers (ECs) spontaneously control plasma human immunodeficiency virus type 1 (HIV-1) RNA without antiretroviral therapy. However, 25% lose virological control over time. The aim of this work was to study the proteomic profile that preceded this loss of virological control to identify potential biomarkers. METHODS: Plasma samples from ECs who spontaneously lost virological control (transient controllers [TCs]), at 2 years and 1 year before the loss of control, were compared with a control group of ECs who persistently maintained virological control during the same follow-up period (persistent controllers [PCs]). Comparative plasma shotgun proteomics was performed with tandem mass tag (TMT) isobaric tag labeling and nanoflow liquid chromatography coupled to Orbitrap mass spectrometry. RESULTS: Eighteen proteins exhibited differences comparing PC and preloss TC timepoints. These proteins were involved in proinflammatory mechanisms, and some of them play a role in HIV-1 replication and pathogenesis and interact with structural viral proteins. Coagulation factor XI, α-1-antichymotrypsin, ficolin-2, 14-3-3 protein, and galectin-3-binding protein were considered potential biomarkers. CONCLUSIONS: The proteomic signature associated with the spontaneous loss of virological control was characterized by higher levels of inflammation, transendothelial migration, and coagulation. Galectin-3 binding protein could be considered as potential biomarker for the prediction of virological progression and as therapeutic target in ECs.
BACKGROUND: Elite controllers (ECs) spontaneously control plasma human immunodeficiency virus type 1 (HIV-1) RNA without antiretroviral therapy. However, 25% lose virological control over time. The aim of this work was to study the proteomic profile that preceded this loss of virological control to identify potential biomarkers. METHODS: Plasma samples from ECs who spontaneously lost virological control (transient controllers [TCs]), at 2 years and 1 year before the loss of control, were compared with a control group of ECs who persistently maintained virological control during the same follow-up period (persistent controllers [PCs]). Comparative plasma shotgun proteomics was performed with tandem mass tag (TMT) isobaric tag labeling and nanoflow liquid chromatography coupled to Orbitrap mass spectrometry. RESULTS: Eighteen proteins exhibited differences comparing PC and preloss TC timepoints. These proteins were involved in proinflammatory mechanisms, and some of them play a role in HIV-1 replication and pathogenesis and interact with structural viral proteins. Coagulation factor XI, α-1-antichymotrypsin, ficolin-2, 14-3-3 protein, and galectin-3-binding protein were considered potential biomarkers. CONCLUSIONS: The proteomic signature associated with the spontaneous loss of virological control was characterized by higher levels of inflammation, transendothelial migration, and coagulation. Galectin-3 binding protein could be considered as potential biomarker for the prediction of virological progression and as therapeutic target in ECs.
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