LC-MS Based-Metabolomics of Serum Samples from Newborns Exposed to Zika Virus: a Pilot Study in Brazil

Regina V. Oliveira, Departamento de Química, Universidade Federal de São Carlos (UFSCar), São Carlos, Brazil (oliveirarv@ufscar.br)
Danielle Z. S. Furtado, Instituto De Ciências Ambientais, Químicas E Farmacêuticas, Universidade Federal De São Paulo (unifesp), São Paulo, Brazil
Luiz André Zanluqui, Instituto De Ciências Ambientais, Químicas E Farmacêuticas, Universidade Federal De São Paulo (unifesp), São Paulo, Brazil
Manuel Pedro B. Silva, Instituto De Ciências Ambientais, Químicas E Farmacêuticas, Universidade Federal De São Paulo (unifesp), São Paulo, Brazil
Cleber N. Barreto, Instituto De Ciências Ambientais, Químicas E Farmacêuticas, Universidade Federal De São Paulo (unifesp), São Paulo, Brazil
Fabiana A. Marques, Instituto Federal De Educação, Ciência E Tecnologia Goiano, Ceres, Brazil
Nilson Antonio Assunção, Instituto De Ciências Ambientais, Químicas E Farmacêuticas, Universidade Federal De São Paulo (unifesp), São Paulo, Brazil

Zika virus (ZIKV) is a flavivirus transmitted by Aedes genus mosquitoes that was identified almost 70 years earlier in Africa, the Zika virus was thought to cause only mild disease. Throughout 2015, increasingly worrisome reports trickled out of Brazil about obscure virus called Zika, which became associated with birth defects, specifically microcephaly, a brain anomalie, and progressive form of paralysis known as Guillain-Barré syndrome, transforming the Zika threat into a worldwide public health emergency. In Brazil, more than 2,100 babies have been born with microencephaly and other birth defects linked to Zika. ZIKV is primary transmitted by the bite of an infected mosquito from Aedes genus, however, it can also be transmitted through sexual intercourse and from mother to fetus during pregnancy (congenital) or around the time of birth (perinatal). Signs and symptoms of ZIKV infection are often mistaken with other common viral infections ranging from no symptoms to severe illness. In light of these, better understanding the pathophysiological mechanism of ZIKV infection and its relation to microencephaly is critical for delivering improved patient care. This work employed metabolomic tools for understanding alterations caused by ZIKV infection in serum from newborns with/without microcephaly. Forty-six serum samples from newborns were divided into groups: 1-Newborns from ZIKV-infected mothers but without microcephaly (n=17) and 2-Newborns from ZIKV-infected mothers and with microcephaly (n=29). Metabolites were analyzed in reversed phase and HILIC separation modes with an UHPLC system (Nexera®, Shimadzu) coupled to an Impact HD QTOF^TM mass spectrometer (Bruker Daltonics) equipped with ESI operating in negative or positive ion mode. The MS and MS/MS data were processed through DataAnalysis and MZmine. The chemometric models were obtained through MetaboAnalyst and the identification of features were performed through the Mass Mediator (http://ceumass.eps.uspceu.es/). Statistical analyses were performed by unsupervised (PCA) and supervised (PLS-DA) chemometric tools based on mass spectral data. Results showed a large number of metabolites identified in the two studied groups, suggesting alterations in important biochemical pathways. Using VIP scores >1.5, 430 features were identified in positive ion mode and 260 features in negative ion mode. The biomarkers detected were classified as aminoacids, lipids, biogenic amines, sugars and other serum metabolites. Correlation of the identified markers with biochemical pathways indicated alterations in serotonin, noradrenaline, adrenaline, and histidine degradation pathways. These data provided information to the biochemical events in newborns exposure to ZIKV, from which it may direct further research during gestational period. 

Acknowledgments:MCTIC/FINEP/FNDCT # 04.16.0054.01,FAPESP, and CAPES.

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Abstract Reference & Short Personal Biography of Presenting Author

Dr. Oliveira is a Senior Research Associate Professor at the Chemistry Department of the Federal University of São Carlos, Brazil where she supervises Senior Researchers, Graduate students, and leads a Bioanalytical Research Laboratory. She works and collaborates on projects including qualitative and quantitative analysis of small and large molecules, natural products, biologics molecules, and biomarkers.
Her main research interest includes drug metabolism, metabolomics, bioanalytical methods for small and large molecules, mass spectrometry, biomarkers assays and cutting-edge bioanalysis methods by LC-MS/MS at the intersection of Analytical Chemistry with Biology, Biochemistry and Chemistry.

Dr. Oliveira joined the National Institute of Health, National Institute on Aging (Baltimore, MD), as a Postdoctoral Research Fellow to investigate new approaches for drug discovery using on-line screening of target molecules and bioaffinity chromatography. She also worked as a Visiting Research Scientist at Quintiles Inc (Ithaca, NY) and acted as a Senior Research Investigator at Bristol-Myers Squibb (Princeton, NJ) in the Pharmaceutical Candidate Optimization Department, where she worked with MS-based assay development for exploratory biomarkers in PK/PD and toxicology studies, collaborating to Discovery and Clinical Research activities.
She has authored or co-authored over 100 journal articles, book chapters and oral/poster presentations and has served as editorial board for the Journal of Pharmaceutical and Biomedical Analysis.