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Zika virus infection induces synthesis of Digoxin in glioblastoma cells

Estela de O. Lima, Tatiane M. Guerreiro, Carlos F. O. R. Melo, Diogo N. de Oliveira, Daisy Machado, Marcelo Lancelloti, Rodrigo R. Catharino
doi: https://doi.org/10.1101/174441
Estela de O. Lima
1Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas - UNICAMP, Campinas, SP, 13083-877, Brazil
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Tatiane M. Guerreiro
1Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas - UNICAMP, Campinas, SP, 13083-877, Brazil
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Carlos F. O. R. Melo
1Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas - UNICAMP, Campinas, SP, 13083-877, Brazil
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Diogo N. de Oliveira
1Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas - UNICAMP, Campinas, SP, 13083-877, Brazil
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Daisy Machado
2Laboratory of Biotechnology, School of Pharmaceutical Sciences, University of Campinas – UNICAMP, Campinas, SP, 13083-859, Brazil
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Marcelo Lancelloti
2Laboratory of Biotechnology, School of Pharmaceutical Sciences, University of Campinas – UNICAMP, Campinas, SP, 13083-859, Brazil
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Rodrigo R. Catharino
1Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas - UNICAMP, Campinas, SP, 13083-877, Brazil
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ABSTRACT

Recently, microcephaly cases have increased in Americas and have been matter of concern due to Zika virus (ZIKV) recent outbreak. Previous studies have shown that ZIKV-infected progenitor neuronal cells present morphological abnormalities and increased rates of cell death, which may be indicators of microcephaly causes. As recent studies indicate Zika virus’ tropism for brain cells, how would a glioblastoma (GBM) lineage behave under ZIKV infection, considering GBM the most common and malignant brain tumor in adults, presenting extreme chemoresistance and high morbidity and mortality rates? The current trend of using genetically engineered oncolytic pathogens as a safe way to eliminate tumors is under development, with trials already in course. Therefore, the present study evaluated the possible oncolytic effects and metabolomic alterations of Zika virus infection at human malignant M059J glioblastoma cells. Microscopic evaluation was performed using optical microscopy, which showed cytopathic effects induced by ZIKV at GBM cells. For the metabolomics study, both control and infected cell cultures were submitted to MALDI-MSI analysis. Mass spectrometry data were submitted to PLS-DA statistical analysis, and distinct biomarkers were elected for each infected groups. This study brings light to unexpectedly induced metabolic changes, as endogenous Digoxin as important biomarker for ZIKV-GBM group, associated with cytopathic effects induced by viral infection. These results evidences that genetically engineered ZIKV might be a potential new strategy for neural cancer management through the induction of endogenous digoxin synthesis in glioblastoma cells.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 09, 2017.
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Zika virus infection induces synthesis of Digoxin in glioblastoma cells
Estela de O. Lima, Tatiane M. Guerreiro, Carlos F. O. R. Melo, Diogo N. de Oliveira, Daisy Machado, Marcelo Lancelloti, Rodrigo R. Catharino
bioRxiv 174441; doi: https://doi.org/10.1101/174441
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Zika virus infection induces synthesis of Digoxin in glioblastoma cells
Estela de O. Lima, Tatiane M. Guerreiro, Carlos F. O. R. Melo, Diogo N. de Oliveira, Daisy Machado, Marcelo Lancelloti, Rodrigo R. Catharino
bioRxiv 174441; doi: https://doi.org/10.1101/174441

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