Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells
(USP) Universidade de São Paulo ; (LNBio) Laboratório Nacional de Biociências ; (UNIFESP) Universidade Federal de São Paulo ; Hospital Israelita Albert Einstein ; (UMC) Universidade de Mogi das Cruzes ; (AACD) Associação de Assistência à Criança Deficiente ; (CRER) Centro de Reabilitação e Readaptação Dr Henrique Santillo ; (UFPE) Universidade Federal de Pernambuco ; (UFRN) Universidade Federal do Rio Grande do Norte ; (ISEA) Instituto de Saúde Elpídio de Almeida ; (UEPB) Universidade Estadual da Paraíba ; (UFBA) Universidade Federal da Bahia ; (FMJ) Faculdade de Medicina de Jundiaí ; (UFS) Universidade Federal de Sergipe
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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.
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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