Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells
Autor(es): Caires-Júnior, Luiz Carlos; Goulart, Ernesto; Melo, Uirá Souto; Araujo, Bruno Henrique Silva; 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; Suárez-Patiño, Sandra Fernanda; Ventini, Daniella Cristina; Silva, Sérgio Gomes da; Yamamoto, Guilherme Lopes; Ezquina, Suzana; Naslavsky, Michel Satya; Telles-Silva, Kayque Alves; Weinmann, Karina; Linden, Vanessa van der; Linden, Helio van der; Oliveira, Jo?o 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 Abr?o; Kalil, Jorge; Cunha-Neto, Edécio; Nakaya, Helder; Andreata-Santos, Robert ; Ferreira, Luis Carlos de Souza; Verjovski-Almeida, Sergio; Lee Ho, Paulo; Passos-Bueno, Maria Rita; Zatz, Mayana
Resumo: 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.
Imprenta: Nature Communications, v. 9, n. 475, 2018
Descritores: Zika virus - Cell; Zika virus - Viral infections
Data de publicação: 2018
