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; Schanoski, Alessandra Soares
; 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
; da Silva, Sergio Gomes; Yamamoto, Guilherme Lopes; Ezquina, Suzana; Naslavsky, Michel Satya; Telles-Silva, Kayque Alves; Weinmann, Karina; Van der Linden, Vanessa; Van der Linden, Helio; Mendes de Oliveira, Joao Ricardo; Rodrigues Arrais, Nivia Maria; Melo, Adriana; Figueiredo, Thalita; Santos, Silvana; Castro Meira, Joanna Goes; Passos, Saulo Duarte; de Almeida, Roque Pacheco; Bispo, Ana Jovina Barreto; Cavalheiro, Esper Abrao; Kalil, Jorge; Cunha-Neto, Edecio; Nakaya, Helder; Santos, Robert Andreata; Ferreira, Luís Carlos de Souza; Verjovski-Almeida, Sergio
; Ho, Paulo Lee
; Passos-Bueno, Maria Rita; Zatz, Mayana








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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Caires-Júnior LC, Goulart E, Melo US, Araujo BHS, Alvizi L, Schanoski AS, et al. Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells. Nat. Commun.. 2018 Feb;9:475. doi:10.1038/s41467-017-02790-9.
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