Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells
Luiz Carlos Caires-Júnior,
Ernesto Goulart,
Uirá Souto Melo,
Bruno Henrique Silva Araujo,
Lucas Alvizi,
Alessandra Soares-Schanoski,
Danyllo Felipe Oliveira,
Gerson Shigeru Kobayashi,
Karina Griesi-Oliveira,
Camila Manso Musso,
Murilo Sena Amaral,
Lucas Ferreira daSilva,
Renato Mancini Astray,
Sandra Fernanda Suárez-Patiño,
Daniella Cristina Ventini,
Sérgio Gomes da Silva,
Guilherme Lopes Yamamoto,
Suzana Ezquina,
Michel Satya Naslavsky,
Kayque Alves Telles-Silva,
Karina Weinmann,
Vanessa van der Linden,
Helio van der Linden,
João Ricardo Mendes Oliveira,
Nivia Maria Rodrigues Arrais,
Adriana Melo,
Thalita Figueiredo,
Silvana Santos,
Joanna Goes Castro Meira,
Saulo Duarte Passos,
Roque Pacheco Almeida,
Ana Jovina Barreto Bispo,
Esper Abrão Cavalheiro,
Jorge Kalil,
Edécio Cunha-Neto,
Helder Nakaya,
Robert Andreata-Santos,
Luis Carlos Souza Ferreira,
Sergio Verjovski-Almeida,
Paulo Lee Ho,
Maria Rita Passos-Bueno and
Mayana Zatz ()
Additional contact information
Luiz Carlos Caires-Júnior: University of São Paulo (USP)
Ernesto Goulart: University of São Paulo (USP)
Uirá Souto Melo: University of São Paulo (USP)
Bruno Henrique Silva Araujo: Brazilian Center for Research in Energy and Materials (CNPEM)
Lucas Alvizi: University of São Paulo (USP)
Alessandra Soares-Schanoski: Butantan Institute
Danyllo Felipe Oliveira: University of São Paulo (USP)
Gerson Shigeru Kobayashi: University of São Paulo (USP)
Karina Griesi-Oliveira: University of São Paulo (USP)
Camila Manso Musso: University of São Paulo (USP)
Murilo Sena Amaral: Butantan Institute
Lucas Ferreira daSilva: University of São Paulo (USP)
Renato Mancini Astray: Butantan Institute
Sandra Fernanda Suárez-Patiño: Butantan Institute
Daniella Cristina Ventini: Butantan Institute
Sérgio Gomes da Silva: Albert Einstein Hospital
Guilherme Lopes Yamamoto: University of São Paulo (USP)
Suzana Ezquina: University of São Paulo (USP)
Michel Satya Naslavsky: University of São Paulo (USP)
Kayque Alves Telles-Silva: University of São Paulo (USP)
Karina Weinmann: University of São Paulo (USP)
Vanessa van der Linden: AACD
Helio van der Linden: Rehabilitation Center—Dr. Henrique Santillo
João Ricardo Mendes Oliveira: Federal University of Pernambuco (UFPE)
Nivia Maria Rodrigues Arrais: Federal University of Rio Grande do Norte (UFRN)
Adriana Melo: ISEA
Thalita Figueiredo: University of São Paulo (USP)
Silvana Santos: Paraíba State University (UEPB)
Joanna Goes Castro Meira: Federal University of Bahia (UFBA)
Saulo Duarte Passos: Medicine School of Jundiaí
Roque Pacheco Almeida: Federal University of Sergipe (UFS)
Ana Jovina Barreto Bispo: Federal University of Sergipe (UFS)
Esper Abrão Cavalheiro: Federal University of São Paulo—UNIFESP/EPM
Jorge Kalil: Butantan Institute
Edécio Cunha-Neto: University of São Paulo (USP)
Helder Nakaya: University of São Paulo (USP)
Robert Andreata-Santos: University of São Paulo (USP)
Luis Carlos Souza Ferreira: University of São Paulo (USP)
Sergio Verjovski-Almeida: Butantan Institute
Paulo Lee Ho: Butantan Institute
Maria Rita Passos-Bueno: University of São Paulo (USP)
Mayana Zatz: University of São Paulo (USP)
Nature Communications, 2018, vol. 9, issue 1, 1-11
Abstract:
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.
Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02790-9
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DOI: 10.1038/s41467-017-02790-9
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