Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells

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art_CAIRES JR._Discordant_congenital_Zika_syndrome_twins_show_differential_in_2018.PDF (2.38 MB)
Citações na Scopus
86
Tipo de produção
article
Data de publicação
2018
Editora
NATURE PUBLISHING GROUP
DOI
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Scopus
Web of Science
PubMed
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Título do Volume
Autores
CAIRES JR., Luiz Carlos de
GOULART, Ernesto
MELO, UiraSouto
ARAUJO, Bruno Silva Henrique
ALVIZI, Lucas
SCHANOSKI, Alessandra Soares
OLIVEIRA, Danyllo Felipe de
KOBAYASHI, Gerson Shigeru
GRIESI-OLIVEIRA, Karina
MUSSO, Camila Manso
Autor de Grupo de pesquisa
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Organizadores
Citação
NATURE COMMUNICATIONS, v.9, article ID 475, 11p, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Congenital Zika syndrome (CZS) causes early brain development impairment by affecting neural progenitor cells (NPCs). Here, we analyze NPCs from three pairs of dizygotic twins discordant for CZS. We compare by RNA-Seq the NPCs derived from CZS-affected and CZS-unaffected twins. Prior to Zika virus (ZIKV) infection the NPCs from CZS babies show a significantly different gene expression signature of mTOR and Wnt pathway regulators, key to a neurodevelopmental program. Following ZIKV in vitro infection, cells from affected individuals have significantly higher ZIKV replication and reduced cell growth. Whole-exome analysis in 18 affected CZS babies as compared to 5 unaffected twins and 609 controls excludes a monogenic model to explain resistance or increased susceptibility to CZS development. Overall, our results indicate that CZS is not a stochastic event and depends on NPC intrinsic susceptibility, possibly related to oligogenic and/or epigenetic mechanisms.
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https://observatorio.fm.usp.br/handle/OPI/25493
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/19
Artigos e Materiais de Revistas Científicas - ODS/03