Zika Virus Impairs Neurogenesis and Synaptogenesis Pathways in Human Neural Stem Cells and Neurons

Author(s):Show less -

Rosa-Fernandes, Livia ^[1] ; Cugola, Fernanda Rodrigues ^[2] ; Russo, Fabiele Baldino ^[2] ; Kawahara, Rebeca ^[3] ; de Melo Freire, Caio Cesar ^[4] ; Correa Leite, Paulo Emlio ^[5] ; Bassi Stern, Ana Carolina ^[3] ; Angeli, Claudia Blanes ^[3] ; Leal de Oliveira, Danielle Bruna ^[2] ; Melo, Stella Rezende ^[2] ; de Andrade Zanotto, Paolo Marinho ^[2] ; Durigon, Edison Luiz ^[2] ; Larsen, Martin Rossel ^[1] ; Baleeiro Beltrao-Braga, Patricia Cristina ^{[6, 2]} ; Palmisano, Giuseppe ^[3]

Affiliation

^[1] Univ Southern Denmark, Dept Biochem & Mol Biol, Odense - Denmark

^[2] Univ Sao Paulo, Dept Microbiol, Inst Biomed Sci, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[4] Univ Fed Sao Carlos, Dept Genet & Evolut, Sao Carlos, SP - Brazil

^[5] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Rio De Janeiro - Brazil

^[6] Univ Sao Paulo, Sch Arts Sci & Humanities, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR NEUROSCIENCE; v. 13, MAR 15 2019.
• Web of Science Citations: 1

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. (AU)

• FAPESP's process: 16/02978-6 - Cell modeling Autism Spectrum Disorder patients using induced pluripotent stem cells (iPSC)
• Grantee: Fabiele Baldino Russo
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 14/06863-3 - Post-translational modifications in cancer and parasite infection diagnosis: methodological approaches and biological implications
• Grantee: Giuseppe Palmisano
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 13/08844-3 - Morphological and functional research of neurons derived from induced pluripotent stem cells from autistic spectrum disorder patients
• Grantee: Fabiele Baldino Russo
• Support type: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/16748-8 - INVESTIGATION OF ZIKA VIRUS ACTION IN CENTRAL NERVOUS SYSTEM CELLS: MODELING INFECTION IN HUMAN ASTROCYTES DERIVED FROM INDUCED PLURIPOTENT CELLS
• Grantee: Patricia Cristina Baleeiro Beltrão Braga
• Support type: Regular Research Grants
• FAPESP's process: 11/20683-0 - Generation of induced pluripotent cells of patients with autistic disorder
• Grantee: Fabiele Baldino Russo
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/02866-0 - DISCOVERY AND VERIFICATION OF INTACT GLYCOPEPTIDES AS CANDIDATE PROSTATE CANCER BIOMARKERS USING MASS SPECTROMETRY-BASED PROTEOMICS APPROACHES
• Grantee: Rebeca Kawahara Sakuma
• Support type: Scholarships in Brazil - Post-Doctorate