Zika virus impairs neurogenesis and synaptogenesis pathways in human neural stem cells and neurons

Livia Rosa-Fernandes, Fernanda Rodrigues Cugola, Fabiele Baldino Russo, Rebeca Kawahara, Caio Cesar de Melo Freire, Paulo Emílio Corrêa Leite, Ana Carolina Bassi Stern, Claudia Blanes Angeli, Danielle Bruna Leal de Oliveira, Stella Rezende Melo, Paolo Marinho de Andrade Zanotto, Edison Luiz Durigon, Martin Røssel Larsen*, Patricia Cristina Baleeiro Beltrão-Braga*, Giuseppe Palmisano*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
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Abstract

Growing evidences have associated Zika virus (ZIKV) infection with congenital malformations, including microcephaly. Nonetheless, signaling mechanisms that promote the disease outcome are far from being understood, affecting the development of suitable therapeutics. In this study, we applied shotgun mass spectrometry (MS)-based proteomics combined with cell biology approaches to characterize altered molecular pathways on human neuroprogenitor cells (NPC) and neurons derived from induced pluripotent stem cells infected by ZIKV-BR strain, obtained from the 2015 Brazilian outbreak. Furthermore, ZIKV-BR infected NPCs showed unique alteration of pathways involved in neurological diseases, cell death, survival and embryonic development compared to ZIKV-AF, showing a human adaptation of the Brazilian viral strain. Besides, infected neurons differentiated from NPC presented an impairment of neurogenesis and synaptogenesis processes. Taken together, these data explain that CNS developmental arrest observed in Congenital Zika Syndrome is beyond neuronal cell death.

Original languageEnglish
Article number64
Pages (from-to)1-16
Number of pages16
JournalFrontiers in Cellular Neuroscience
Volume13
DOIs
Publication statusPublished - 15 Mar 2019
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Zika virus
  • microcephaly
  • congenital Zika syndrome
  • neurogenesis
  • synaptogenesis

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