Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.
Nat Commun
; 9(1): 475, 2018 02 02.
Article
in En
| MEDLINE
| ID: mdl-29396410
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Twins, Dizygotic
/
Brain
/
Gene Expression
/
Neural Stem Cells
/
Zika Virus Infection
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Infant
/
Male
/
Newborn
Country/Region as subject:
America do sul
/
Brasil
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2018
Document type:
Article
Affiliation country: