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

^*Kontaktforfatter

University of São Paulo
Departamento de Genética e Evolução
Federal University of Rio de Janeiro

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › 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.

Originalsprog	Engelsk
Artikelnummer	64
Tidsskrift	Frontiers in Cellular Neuroscience
Vol/bind	13
Antal sider	16
ISSN	1662-5102
DOI	https://doi.org/10.3389/fncel.2019.00064
Status	Udgivet - 15. mar. 2019

Finansiering

LR-F was supported by CNPq (202077/2015-2). RK was supported by FAPESP (2015/02866-0). PZ was supported by CNPq (441105/2016-5). PB-B was supported by FAPESP (2011/20683-0, 2013/08844-3, 2016/02978-6, and 2018/16748-8), the NGO “The Tooth Fairy Project” and CAPES for Ph.D. fellowship. GP was supported by FAPESP (2014/06863-3), CNPq (441878/2014-8) and Ricerca Finalizzata (Convenzione n.172/GR-2011-02350301) from the Ministero della Salute. This work was also supported by the VILLUM Center for Bioanalytical Sciences at the University of Southern Denmark.

Dokumenter og links

10.3389/fncel.2019.00064Licens: CC BY

Zika virus impairs neurogenesis and synaptogenesis pathways in human neural stem cells and neuronsForlagets udgivne version, 4,41 MBLicens: CC BY

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Tjek adgangen til materialet i Syddansk Universitetsbiblioteks søgemaskine

Citationsformater

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, Artikel 64. https://doi.org/10.3389/fncel.2019.00064

@article{59b2660964f541d995755aca98f225c8,

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 = "Congenital Zika syndrome, Microcephaly, Neurogenesis, Synaptogenesis, Zika virus",

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",

year = "2019",

month = mar,

day = "15",

doi = "10.3389/fncel.2019.00064",

language = "English",

volume = "13",

journal = "Frontiers in Cellular Neuroscience",

issn = "1662-5102",

publisher = "Frontiers Media",

}

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, bind 13, 64. 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

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 - Congenital Zika syndrome

KW - Microcephaly

KW - Neurogenesis

KW - Synaptogenesis

KW - Zika virus

U2 - 10.3389/fncel.2019.00064

DO - 10.3389/fncel.2019.00064

M3 - Journal article

C2 - 30949028

AN - SCOPUS:85064233264

SN - 1662-5102

VL - 13

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

Abstract

Finansiering

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