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Nat Commun. 2018 Feb 2;9(1):475. doi: 10.1038/s41467-017-02790-9.

Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.

Author information

1
Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo (USP), São Paulo - SP, 05508-900, Brazil.
2
Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas - SP, 13083-970, Brazil.
3
Neuroscience laboratory, Department of Neurology and Neurosurgery, Federal University of São Paulo-UNIFESP/EPM, São Paulo - SP, 04039-002, Brazil.
4
Butantan Institute, São Paulo - SP, 05503-900, Brazil.
5
Albert Einstein Hospital, São Paulo - SP, 05652-900, Brazil.
6
Department of Biochemistry, Institute of Chemistry, University of São Paulo (USP), São Paulo - SP, 05508-900, Brazil.
7
Universidade de Mogi das Cruzes, Mogi das Cruzes - SP, 08780-911, Brazil.
8
AACD, Recife - PE, 50080-810, Brazil.
9
Rehabilitation Center-Dr. Henrique Santillo, Goiânia - GO, 74653-230, Brazil.
10
Neuropsychiatry Department and KeizoAsami Laboratory, Federal University of Pernambuco (UFPE), Recife - PE, 50670-901, Brazil.
11
Department of Pediatrics, Federal University of Rio Grande do Norte (UFRN), Natal- RN, 59010-180, Brazil.
12
ISEA, Campina Grande- PB, 58400-220, Brazil.
13
Department of Biology, Paraíba State University (UEPB), Campina Grande - PB, 58429-500, Brazil.
14
Federal University of Bahia (UFBA), Salvador - BA, 40170-115, Brazil.
15
Infectious pediatric laboratory, Medicine School of Jundiaí, Jundiaí - SP, 13202-550, Brazil.
16
Division of Immunology and Molecular Biology Laboratory, Federal University of Sergipe (UFS), Aracaju - SP, 49100-000, Brazil.
17
Heart Institute, Faculty of Medicine, University of São Paulo (USP), São Paulo - SP, 05403-900, Brazil.
18
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo - SP, 05508-900, Brazil.
19
Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Science, University of São Paulo (USP), São Paulo - SP, 05508-900, Brazil.
20
Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo (USP), São Paulo - SP, 05508-900, Brazil. mayazatz@usp.br.

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.

PMID:
29396410
PMCID:
PMC5797251
DOI:
10.1038/s41467-017-02790-9
[Indexed for MEDLINE]
Free PMC Article

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