Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection
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J. Virol.-2017-Cui-.pdf
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Author(s)
Cui, Liang
Hou, Jue
Fang, Jinling
Lee, Yie Hou
Costa, Vivian Vasconcelos
Wong, Lan Hiong
Chen, Qingfeng
Ooi, Eng Eong
Ong, Choon Nam
Tannenbaum, Steven R
Date Issued
May 2017
Journal
Journal of Virology
Publisher
American Society for Microbiology
Citation
Cui, Liang et al. “Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection.” Edited by Jae U. Jung. Journal of Virology 91, 14 (May 2017): e00386–17 © 2017 Cui et al
Version
Final published version
Abstract
Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend-most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. Keywords: dengue fever; humanized mice; mass spectrometry; metabolomics; systems biology
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1128/JVI.00386-17
