LC-MS/MS - NS-NE - Zika Virus Impairs Neurogenesis and Synaptogenesis Pathways in Human Neural Stem Cells and Neurons

ABSTRACT: Growing evidences have associated Zika virus 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-based proteomics combined with cell biology approaches to characterize altered molecular pathways on neurons and NPCs infected by ZIKV-BR, strain obtained from the 2015 Brazilian outbreak. Assessment of neurons differentiated from iPSC from different donors shows the importance of the host genetic background to the susceptibility of ZIKV infection, also confirmed by cytokine fingerprinting. Additionally, infected cells presented an impairment of neurogenesis and synaptogenesis processes. Moreover, ZIKV-BR infected NPCs showed unique alteration of pathways involved in neurological diseases, cell death and survival and embryonic development compared to ZIKV-AF, showing a human adaptation of the Brazilian viral strain. Taken together, these data explain CNS developmental arrest observed in Congenital Zika Virus syndrome is beyond neuronal cell death.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell

SUBMITTER: Livia Rosa-Fernandes  

LAB HEAD: Giuseppe Palmisano

PROVIDER: PXD009293 | Pride | 2019-11-12

REPOSITORIES: Pride