Univ Sao Paulo, Fac Med, Heart Inst, BR-05403900 Sao Paulo, SP - Brazil
 Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508900 Sao Paulo, SP - Brazil
 Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Vaccine Dev Lab, BR-05508900 Sao Paulo, SP - Brazil
Número total de Afiliações: 21
Tipo de documento:
FEB 2 2018.
Citações Web of Science:
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. (AU)