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Dynamics of human hepatic cells metabolome during dengue virus infection
Author(s) -
ElBacha Tatiana,
Galina Antonio,
Almeida Fabio C,
Da Poian Andrea T
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.917.1
Subject(s) - metabolome , glycolysis , pentose phosphate pathway , dengue virus , biology , biochemistry , intracellular , metabolic pathway , fructose , intracellular parasite , metabolism , dihydroxyacetone phosphate , flavivirus , metabolomics , oxidative phosphorylation , metabolite , dengue fever , virus , virology , phosphate , bioinformatics
The metabolic resources crucial for viral replication are provided by host cells. The mechanisms by which viruses interact with cell metabolism, driving biosynthetic molecules for their own replication, however, are unknown. We employed nuclear magnetic resonance to study metabolic fluxes and identify metabolites in dengue virus (DenV) infection of human hepatic cells since liver dysfunction plays a central role in DenV pathogenesis. Metabolomics were done at 24h of infection. 13 C spectra were acquired after cell incubation with D‐[U‐ 13 C]glucose. Results showed that glycolytic (fructose‐6‐phosphate, fructose‐1,6‐bisphosphate, dihydroxyacetone phosphate and glyceraldehyde‐3‐phosphate) and pentose phosphate pathway (PPP; 6‐phosphogluconate) intracellular intermediates were decreased in DenV infection and so was lactate accumulation in culture medium. Intracellular L‐glutamate and L‐alanine were increased upon DenV infection. The decrease in glycolytic and PPP intermediates indicates an enhancement of glucose utilization for biosynthetic purposes; Increased contents of L‐aminoacids indicates decreased oxidative metabolism suggesting impaired mitochondrial function. The use of metabolomics to evaluate carbon fluxes represents a key step towards the elucidation of the dynamics of DenV‐human hepatic cells metabolic interactions. Supported by: CAPES, CNPq and FAPERJ.