Frontiers in cellular neuroscience · 2019
Zika Virus Impairs Neurogenesis and Synaptogenesis Pathways in Human Neural Stem Cells and Neurons.
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Rosa-Fernandes Livia, Cugola Fernanda Rodrigues, Russo Fabiele Baldino, Kawahara Rebeca, de Melo Freire Caio Cesar, Leite Paulo Emílio Corrêa, Bassi Stern Ana Carolina, Angeli Claudia Blanes, de Oliveira Danielle Bruna Leal, Melo Stella Rezende, Zanotto Paolo Marinho de Andrade, Durigon Edison Luiz, Larsen Martin Røssel, Beltrão-Braga Patricia Cristina Baleeiro, Palmisano Giuseppe
Аннотация
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.