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 - http://www.scopus.com/inward/record.url?scp=85064233264&partnerID=8YFLogxK
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 -