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

doi:10.3389/fncel.2019.00064

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 journal › Article › peer-review

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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 language	English
Article number	64
Pages (from-to)	1-16
Number of pages	16
Journal	Frontiers in Cellular Neuroscience
Volume	13
DOIs	https://doi.org/10.3389/fncel.2019.00064
Publication status	Published - 15 Mar 2019
Externally published	Yes

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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10.3389/fncel.2019.00064

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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, 1-16. Article 64. https://doi.org/10.3389/fncel.2019.00064

@article{40b03457aea343e5b9830b5268266306,

title = "Zika virus impairs neurogenesis and synaptogenesis pathways in human neural stem cells and neurons",

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.",

keywords = "Zika virus, microcephaly, congenital Zika syndrome, neurogenesis, synaptogenesis",

author = "Livia Rosa-Fernandes and Cugola, \{Fernanda Rodrigues\} and Russo, \{Fabiele Baldino\} and Rebeca Kawahara and \{de Melo Freire\}, \{Caio Cesar\} and Leite, \{Paulo Em{\'i}lio Corr{\^e}a\} and \{Bassi Stern\}, \{Ana Carolina\} and Angeli, \{Claudia Blanes\} and \{de Oliveira\}, \{Danielle Bruna Leal\} and Melo, \{Stella Rezende\} and Zanotto, \{Paolo Marinho de Andrade\} and Durigon, \{Edison Luiz\} and Larsen, \{Martin R{\o}ssel\} and Beltr{\~a}o-Braga, \{Patricia Cristina Baleeiro\} and Giuseppe Palmisano",

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.",

year = "2019",

month = mar,

day = "15",

doi = "10.3389/fncel.2019.00064",

language = "English",

volume = "13",

pages = "1--16",

journal = "Frontiers in Cellular Neuroscience",

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Rosa-Fernandes, L, Cugola, FR, Russo, FB, Kawahara, R, de Melo Freire, CC, Leite, PEC, Bassi Stern, AC, Angeli, CB, de Oliveira, DBL, Melo, SR, Zanotto, PMDA, Durigon, EL, Larsen, MR, Beltrão-Braga, PCB & Palmisano, G 2019, 'Zika virus impairs neurogenesis and synaptogenesis pathways in human neural stem cells and neurons', Frontiers in Cellular Neuroscience, vol. 13, 64, pp. 1-16. https://doi.org/10.3389/fncel.2019.00064

TY - JOUR

T1 - Zika virus impairs neurogenesis and synaptogenesis pathways in human neural stem cells and neurons

AU - Rosa-Fernandes, Livia

AU - Cugola, Fernanda Rodrigues

AU - Russo, Fabiele Baldino

AU - Kawahara, Rebeca

AU - de Melo Freire, Caio Cesar

AU - Leite, Paulo Emílio Corrêa

AU - Bassi Stern, Ana Carolina

AU - Angeli, Claudia Blanes

AU - de Oliveira, Danielle Bruna Leal

AU - Melo, Stella Rezende

AU - Zanotto, Paolo Marinho de Andrade

AU - Durigon, Edison Luiz

AU - Larsen, Martin Røssel

AU - Beltrão-Braga, Patricia Cristina Baleeiro

AU - Palmisano, Giuseppe

N1 - 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.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - 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.

AB - 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.

KW - Zika virus

KW - microcephaly

KW - congenital Zika syndrome

KW - neurogenesis

KW - synaptogenesis

UR - https://www.scopus.com/pages/publications/85064233264

U2 - 10.3389/fncel.2019.00064

DO - 10.3389/fncel.2019.00064

M3 - Article

C2 - 30949028

SN - 1662-5102

VL - 13

SP - 1

EP - 16

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

M1 - 64

ER -

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

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