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Title: Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018)
Authors: Caires-Junior, Luiz Carlos
Goulart, Ernesto
Melo, Uira Souto
Araujo, Bruno Henrique Silva [UNIFESP]
Alvizi, Lucas
Soares-Schanoski, Alessandra
Oliveira, Danyllo Felipe de
Kobayashi, Gerson Shigeru
Griesi-Oliveira, Karina
Musso, Camila Manso
Amaral, Murilo Sena
Silva, Lucas Ferreira da
Astray, Renato Mancini
Suarez-Patino, Sandra Fernanda
Ventini, Daniella Cristina
Silva, Sergio Gomes da
Yamamoto, Guilherme Lopes
Ezquina, Suzana
Naslavsky, Michel Satya
Telles-Silva, Kayque Alves
Weinmann, Karina
van der Linden, Vanessa
van der Linden, Helio
Oliveira, Joao Ricardo Mendes de
Arrais, Nivia Maria Rodrigues
Melo, Adriana
Figueiredo, Thalita
Santos, Silvana
Meira, Joanna Goes Castro
Passos, Saulo Duarte
Almeida, Roque Pacheco de
Bispo, Ana Jovina Barreto
Cavalheiro, Esper Abrão [UNIFESP]
Kalil, Jorge
Cunha-Neto, Edecio
Nakaya, Helder
Andreata-Santos, Robert
Ferreira, Luis Carlos de Souza
Verjovski-Almeida, Sergio
Ho, Paulo Lee
Passos-Bueno, Maria Rita
Zatz, Mayana
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Nature Communications. London, v. 9, 2018.
Abstract: 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.
ISSN: 2041-1723
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