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

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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.

TidsskriftFrontiers in cellular neuroscience
Antal sider16
StatusUdgivet - 15. mar. 2019



Rosa-Fernandes, L., Cugola, F. R., Russo, F. B., Kawahara, R., de Melo Freire, C. C., Leite, P. E. C., Bassi Stern, A. C., Angeli, C. B., de Oliveira, D. B. L., Melo, S. R., Zanotto, P. M. D. A., Durigon, E. L., Larsen, M. R., Beltrão-Braga, P. C. B., & Palmisano, G. (2019). Zika virus impairs neurogenesis and synaptogenesis pathways in human neural stem cells and neurons. Frontiers in cellular neuroscience, 13, [64]. https://doi.org/10.3389/fncel.2019.00064