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

Author

Listed:
  • 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)
    Federal University of São Paulo—UNIFESP/EPM)

  • 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)
    Albert Einstein Hospital)

  • 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
    Universidade de Mogi das Cruzes)

  • 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
    University of São Paulo (USP))

  • Paulo Lee Ho

    (Butantan Institute)

  • Maria Rita Passos-Bueno

    (University of São Paulo (USP))

  • Mayana Zatz

    (University of São Paulo (USP))

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.

Suggested Citation

  • 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 G, 2018. "Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02790-9
    DOI: 10.1038/s41467-017-02790-9
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