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Zika Virus Strains and Dengue Virus Induce Distinct Proteomic Changes in Neural Stem Cells and Neurospheres

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Nascimento, Juliana Minardi ; Gouvea-Junqueira, Danielle ; Zuccoli, Giuliana S. ; Gouveia Pedrosa, Carolina da Silva ; Brandao-Teles, Caroline ; Crunfli, Fernanda ; Antunes, Andre S. L. M. ; Cassoli, Juliana S. ; Karmirian, Karina ; Salerno, Jose Alexandre ; de Souza, Gabriela Fabiano ; Muraro, Stefanie Primon ; Proenca-Modena, Jose Luiz ; Higa, Luiza M. ; Tanuri, Amilcar ; Garcez, Patricia P. ; Rehen, Stevens K. ; Martins-de-Souza, Daniel
Total Authors: 18
Document type: Journal article
Source: Molecular Neurobiology; v. N/A, p. 15-pg., 2022-06-22.
Abstract

Brain abnormalities and congenital malformations have been linked to the circulating strain of Zika virus (ZIKV) in Brazil since 2016 during the microcephaly outbreak; however, the molecular mechanisms behind several of these alterations and differential viral molecular targets have not been fully elucidated. Here we explore the proteomic alterations induced by ZIKV by comparing the Brazilian (Br ZIKV) and the African (MR766) viral strains, in addition to comparing them to the molecular responses to the Dengue virus type 2 (DENV). Neural stem cells (NSCs) derived from induced pluripotent stem (iPSCs) were cultured both as monolayers and in suspension (resulting in neurospheres), which were then infected with ZIKV (Br ZIKV or ZIKV MR766) or DENV to assess alterations within neural cells. Large-scale proteomic analyses allowed the comparison not only between viral strains but also regarding the two- and three-dimensional cellular models of neural cells derived from iPSCs, and the effects on their interaction. Altered pathways and biological processes were observed related to cell death, cell cycle dysregulation, and neurogenesis. These results reinforce already published data and provide further information regarding the biological alterations induced by ZIKV and DENV in neural cells. (AU)

FAPESP's process: 18/25439-9 - Proteomic profile of neural stem cells and neurospheres infected with Zika virus and Dengue virus
Grantee:Danielle Gouvêa Junqueira
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 14/21035-0 - Quantitative proteomics in neural cell lines and organoids derived from induced pluripotent stem cells from schizophrenia patients
Grantee:Juliana Minardi Nascimento
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 17/25055-3 - The role of hnRNPs in oligodendrocytes and their implications on schizophrenia
Grantee:Caroline Brandão Teles Rodrigues
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/14666-4 - Influence of the endocannabinoid system on the energetic profile of neural cells during neurodevelopment: implications in Schizophrenia
Grantee:Giuliana da Silva Zuccoli
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 19/00098-7 - Multi-User Equipment approved in grant 2017/25588-1: cromatógrafo Acquity UPLC I-Class
Grantee:Daniel Martins-de-Souza
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 20/10282-7 - Exploring the molecular basis of SARS-CoV-2 infection in preclinical neural models
Grantee:Andre Saraiva Leao Marcelo Antunes
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study
Grantee:Daniel Martins-de-Souza
Support Opportunities: Research Projects - Thematic Grants