Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/progression.
Por:
Gómez-Archila LG, Palomino-Schätzlein M, Zapata-Builes W, Rugeles MT and Galeano E
Publicada:
29 jun 2023
Resumen:
How the human body reacts to the exposure of HIV-1 is an important research goal. Frequently, HIV exposure leads to infection, but some individuals show natural resistance to this infection; they are known as HIV-1-exposed but seronegative (HESN). Others, although infected but without antiretroviral therapy, control HIV-1 replication and progression to AIDS; they are named controllers, maintaining low viral levels and an adequate count of CD4 + T lymphocytes. Biological mechanisms explaining these phenomena are not precise. In this context, metabolomics emerges as a method to find metabolites in response to pathophysiological stimuli, which can help to establish mechanisms of natural resistance to HIV-1 infection and its progression. We conducted a cross-sectional study including 30 HESN, 14 HIV-1 progressors, 14 controllers and 30 healthy controls. Plasma samples (directly and deproteinized) were analyzed through Nuclear Magnetic Resonance (NMR) metabolomics to find biomarkers and altered metabolic pathways. The metabolic profile analysis of progressors, controllers and HESN demonstrated significant differences with healthy controls when a discriminant analysis (PLS-DA) was applied. In the discriminant models, 13 metabolites associated with HESN, 14 with progressors and 12 with controllers were identified, which presented statistically significant mean differences with healthy controls. In progressors, the metabolites were related to high energy expenditure (creatinine), mood disorders (tyrosine) and immune activation (lipoproteins), phenomena typical of the natural course of the infection. In controllers, they were related to an inflammation-modulating profile (glutamate and pyruvate) and a better adaptive immune system response (acetate) associated with resistance to progression. In the HESN group, with anti-inflammatory (lactate and phosphocholine) and virucidal (lactate) effects which constitute a protective profile in the sexual transmission of HIV. Concerning the significant metabolites of each group, we identified 24 genes involved in HIV-1 replication or virus proteins that were all altered in progressors but only partially in controllers and HESN. In summary, our results indicate that exposure to HIV-1 in HESN, as well as infection in progressors and controllers, affects the metabolism of individuals and that this affectation can be determined using NMR metabolomics.
Filiaciones:
Gómez-Archila LG:
Grupo de Investigación en Sustancias Bioactivas, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia (UdeA), Medellín, Colombia
Grupo de Investigación en Ciencias Farmacéuticas ICIF-CES, Facultad de Ciencias y Biotecnología, Universidad CES, Medellín, Colombia
:
Servicio de RMN, Centro de Investigación Príncipe Felipe, Valencia, España
Zapata-Builes W:
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Medellín, Colombia
Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia
Rugeles MT:
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Medellín, Colombia
Galeano E:
Grupo de Investigación en Sustancias Bioactivas, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia (UdeA), Medellín, Colombia
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