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DOI 10.1038/s41467-017-02790-9

Медицинская библиотека · Nature communications · 2018

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

Caires-Júnior Luiz Carlos, Goulart Ernesto, Melo Uirá Souto, Araujo Bruno Henrique Silva, Alvizi Lucas, Soares-Schanoski Alessandra, de Oliveira Danyllo Felipe, Kobayashi Gerson Shigeru, Griesi-Oliveira Karina, Musso Camila Manso, Amaral Murilo Sena, daSilva Lucas Ferreira, Astray Renato Mancini, Suárez-Patiño Sandra Fernanda, Ventini Daniella Cristina, Gomes da Silva Sérgio, Yamamoto Guilherme Lopes, Ezquina Suzana, Naslavsky Michel Satya, Telles-Silva Kayque Alves, Weinmann Karina, van der Linden Vanessa, van der Linden Helio, de Oliveira João Ricardo Mendes, Arrais Nivia Maria Rodrigues, Melo Adriana, Figueiredo Thalita, Santos Silvana, Meira Joanna Goes Castro, Passos Saulo Duarte, de Almeida Roque Pacheco, Bispo Ana Jovina Barreto, Cavalheiro Esper Abrão, Kalil Jorge, Cunha-Neto Edécio, Nakaya Helder, Andreata-Santos Robert, de Souza Ferreira Luis Carlos, Verjovski-Almeida Sergio, Ho Paulo Lee, Passos-Bueno Maria Rita, Zatz Mayana

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Аннотация

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.

Для цитирования: Caires-Júnior Luiz Carlos, Goulart Ernesto, Melo Uirá Souto, Araujo Bruno Henrique Silva, Alvizi Lucas, Soares-Schanoski Alessandra, de Oliveira Danyllo Felipe, Kobayashi Gerson Shigeru, Griesi-Oliveira Karina, Musso Camila Manso, Amaral Murilo Sena, daSilva Lucas Ferreira, Astray Renato Mancini, Suárez-Patiño Sandra Fernanda, Ventini Daniella Cristina, Gomes da Silva Sérgio, Yamamoto Guilherme Lopes, Ezquina Suzana, Naslavsky Michel Satya, Telles-Silva Kayque Alves, Weinmann Karina, van der Linden Vanessa, van der Linden Helio, de Oliveira João Ricardo Mendes, Arrais Nivia Maria Rodrigues, Melo Adriana, Figueiredo Thalita, Santos Silvana, Meira Joanna Goes Castro, Passos Saulo Duarte, de Almeida Roque Pacheco, Bispo Ana Jovina Barreto, Cavalheiro Esper Abrão, Kalil Jorge, Cunha-Neto Edécio, Nakaya Helder, Andreata-Santos Robert, de Souza Ferreira Luis Carlos, Verjovski-Almeida Sergio, Ho Paulo Lee, Passos-Bueno Maria Rita, Zatz Mayana. Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.. Nature communications. 2018. DOI: 10.1038/s41467-017-02790-9.

Предметные рубрики MeSH

BrainBrazilCase-Control StudiesFemaleGene ExpressionGenetic Predisposition to DiseaseHigh-Throughput Nucleotide SequencingHumansInduced Pluripotent Stem CellsInfantInfant, NewbornMaleNeural Stem CellsSequence Analysis, RNATOR Serine-Threonine KinasesTwins, DizygoticWnt Signaling PathwayZika Virus Infection
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