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1H NUCLEAR MAGNETIC RESONANCE METABOLOMICS OF PLASMA UNVEILS LIVER DYSFUNCTION IN DENGUE PATIENTS
Dengue / patologia
Hepatopatias / diagnóstico
Espectroscopia de Ressonância Magnética
Metabolômica
Plasma / Química
Author
Affilliation
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Departamento de Doenças Endêmicas Samuel Pessoa. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Centro Nacional de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil / University of Pittsburgh. Center for Vaccine Research. Pittsburgh, Pennsylvania, USA.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Departamento de Doenças Endêmicas Samuel Pessoa. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brazil / Universidade Federal do Rio de Janeiro. Centro Nacional de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia e Terapia Experimental. Recife, PE, Brasil / University of Pittsburgh. Center for Vaccine Research. Pittsburgh, Pennsylvania, USA.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brazil.
Abstract
Dengue, due to its global burden, is the most important arthropod-borne flavivirus disease, and early detection lowers fatality rates to below 1%. Since the metabolic resources crucial for viral replication are provided by host cells, detection of changes in the metabolic profile associated with disease pathogenesis could help with the identification of markers of prognostic and diagnostic importance. We applied (1)H nuclear magnetic resonance exploratory metabolomics to study longitudinal changes in plasma metabolites in a cohort in Recife, Brazil. To gain statistical power, we used innovative paired multivariate analyses to discriminate individuals with primary and secondary infection presenting as dengue fever (DF; mild) and dengue hemorrhagic fever (DHF; severe) and subjects with a nonspecific nondengue (ND) illness (ND subjects). Our results showed that a decrease in plasma low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) discriminated dengue virus (DENV)-infected subjects from ND subjects, and also, subjects with severe infection even presented a decrease in lipoprotein concentrations compared to the concentrations in subjects with mild infection. These results add to the ongoing discussion that the manipulation of lipid metabolism is crucial for DENV replication and infection. In addition, a decrease in plasma glutamine content was characteristic of DENV infection and disease severity, and an increase in plasma acetate levels discriminated subjects with DF and DHF from ND subjects. Several other metabolites shown to be altered in DENV infection and the implications of these alterations are discussed. We hypothesize that these changes in the plasma metabolome are suggestive of liver dysfunction, could provide insights into the underlying molecular mechanisms of dengue virus pathogenesis, and could help to discriminate individuals at risk of the development of severe infection and predict disease outcome.
DeCS
Dengue / complicaçõesDengue / patologia
Hepatopatias / diagnóstico
Espectroscopia de Ressonância Magnética
Metabolômica
Plasma / Química
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