Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018)
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://dx.doi.org/10.1038/s41467-017-02790-9 https://repositorio.unifesp.br/handle/11600/55823 |
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. |
id |
UFSP_2399784172e16e5a10b027f6243ff2ed |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br/:11600/55823 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018)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.Univ Sao Paulo, Biosci Inst, Human Genome & Stem Cell Res Ctr, Dept Genet & Evolutionary Biol, BR-05508900 Sao Paulo, SP, BrazilBrazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP, BrazilFed Univ Sao Paulo UNIFESP, EPM, Dept Neurol & Neurosurg, Neurosci Lab, BR-04039002 Sao Paulo, SP, BrazilButantan Inst, BR-05503900 Sao Paulo, SP, BrazilAlbert Einstein Hosp, BR-05652900 Sao Paulo, SP, BrazilUniv Sao Paulo, Inst Chem, Dept Biochem, BR-05508900 Sao Paulo, SP, BrazilUniv Mogi das Cruzes, BR-08780911 Mogi Das Cruzes, SP, BrazilAACD, BR-50080810 Recife, PE, BrazilRehabil Ctr Dr Henrique Santillo, BR-74653230 Goiania, Go, BrazilFed Univ Pernambuco UFPE, Neuropsychiat Dept, BR-50670901 Recife, PE, BrazilFed Univ Pernambuco UFPE, KeizoAsami Lab, BR-50670901 Recife, PE, BrazilFed Univ Rio Grande do Norte UFRN, Dept Pediat, BR-59010180 Natal, RN, BrazilISEA, BR-58400220 Campina Grande, PB, BrazilParaiba State Univ UEPB, Dept Biol, BR-58429500 Campina Grande, PB, BrazilFed Univ Bahia UFBA, BR-40170115 Salvador, BA, BrazilMed Sch Jundiai, Infect Pediat Lab, BR-40170115 Jundiai, SP, BrazilFed Univ Sergipe UFS, Div Immunol, BR-49100000 Aracaju, SP, BrazilFed Univ Sergipe UFS, Mol Biol Lab, BR-49100000 Aracaju, SP, BrazilUniv Sao Paulo, Fac Med, Heart Inst, BR-05403900 Sao Paulo, SP, BrazilUniv Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508900 Sao Paulo, SP, BrazilUniv Sao Paulo, Inst Biomed Sci, Dept Microbiol, Vaccine Dev Lab, BR-05508900 Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, EPM, Dept Neurol & Neurosurg, Neurosci Lab, BR-04039002 Sao Paulo, SP, BrazilWeb of ScienceCAPESDECIT-MSNature Publishing Group2020-07-20T16:31:15Z2020-07-20T16:31:15Z2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion-application/pdfhttp://dx.doi.org/10.1038/s41467-017-02790-9Nature Communications. London, v. 9, 2018.10.1038/s41467-017-02790-9WOS000427248800003a.pdf2041-1723https://repositorio.unifesp.br/handle/11600/55823WOS:000427248800003aengNature CommunicationsLondoninfo:eu-repo/semantics/openAccessCaires-Junior, Luiz CarlosGoulart, ErnestoMelo, Uira SoutoAraujo, Bruno Henrique Silva [UNIFESP]Alvizi, LucasSoares-Schanoski, AlessandraOliveira, Danyllo Felipe deKobayashi, Gerson ShigeruGriesi-Oliveira, KarinaMusso, Camila MansoAmaral, Murilo SenaSilva, Lucas Ferreira daAstray, Renato ManciniSuarez-Patino, Sandra FernandaVentini, Daniella CristinaSilva, Sergio Gomes daYamamoto, Guilherme LopesEzquina, SuzanaNaslavsky, Michel SatyaTelles-Silva, Kayque AlvesWeinmann, Karinavan der Linden, Vanessavan der Linden, HelioOliveira, Joao Ricardo Mendes deArrais, Nivia Maria RodriguesMelo, AdrianaFigueiredo, ThalitaSantos, SilvanaMeira, Joanna Goes CastroPassos, Saulo DuarteAlmeida, Roque Pacheco deBispo, Ana Jovina BarretoCavalheiro, Esper Abrão [UNIFESP]Kalil, JorgeCunha-Neto, EdecioNakaya, HelderAndreata-Santos, RobertFerreira, Luis Carlos de SouzaVerjovski-Almeida, SergioHo, Paulo LeePassos-Bueno, Maria RitaZatz, Mayanareponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-03T08:35:50Zoai:repositorio.unifesp.br/:11600/55823Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-03T08:35:50Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018) |
title |
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018) |
spellingShingle |
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018) Caires-Junior, Luiz Carlos |
title_short |
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018) |
title_full |
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018) |
title_fullStr |
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018) |
title_full_unstemmed |
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018) |
title_sort |
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018) |
author |
Caires-Junior, Luiz Carlos |
author_facet |
Caires-Junior, Luiz Carlos Goulart, Ernesto Melo, Uira Souto Araujo, Bruno Henrique Silva [UNIFESP] 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 Suarez-Patino, Sandra Fernanda Ventini, Daniella Cristina Silva, Sergio Gomes da Yamamoto, Guilherme Lopes Ezquina, Suzana Naslavsky, Michel Satya Telles-Silva, Kayque Alves Weinmann, Karina van der Linden, Vanessa van der Linden, Helio Oliveira, Joao 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 Abrão [UNIFESP] Kalil, Jorge Cunha-Neto, Edecio Nakaya, Helder Andreata-Santos, Robert Ferreira, Luis Carlos de Souza Verjovski-Almeida, Sergio Ho, Paulo Lee Passos-Bueno, Maria Rita Zatz, Mayana |
author_role |
author |
author2 |
Goulart, Ernesto Melo, Uira Souto Araujo, Bruno Henrique Silva [UNIFESP] 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 Suarez-Patino, Sandra Fernanda Ventini, Daniella Cristina Silva, Sergio Gomes da Yamamoto, Guilherme Lopes Ezquina, Suzana Naslavsky, Michel Satya Telles-Silva, Kayque Alves Weinmann, Karina van der Linden, Vanessa van der Linden, Helio Oliveira, Joao 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 Abrão [UNIFESP] Kalil, Jorge Cunha-Neto, Edecio Nakaya, Helder Andreata-Santos, Robert Ferreira, Luis Carlos de Souza Verjovski-Almeida, Sergio Ho, Paulo Lee Passos-Bueno, Maria Rita Zatz, Mayana |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Caires-Junior, Luiz Carlos Goulart, Ernesto Melo, Uira Souto Araujo, Bruno Henrique Silva [UNIFESP] 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 Suarez-Patino, Sandra Fernanda Ventini, Daniella Cristina Silva, Sergio Gomes da Yamamoto, Guilherme Lopes Ezquina, Suzana Naslavsky, Michel Satya Telles-Silva, Kayque Alves Weinmann, Karina van der Linden, Vanessa van der Linden, Helio Oliveira, Joao 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 Abrão [UNIFESP] Kalil, Jorge Cunha-Neto, Edecio Nakaya, Helder Andreata-Santos, Robert Ferreira, Luis Carlos de Souza Verjovski-Almeida, Sergio Ho, Paulo Lee Passos-Bueno, Maria Rita Zatz, Mayana |
description |
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. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 2020-07-20T16:31:15Z 2020-07-20T16:31:15Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1038/s41467-017-02790-9 Nature Communications. London, v. 9, 2018. 10.1038/s41467-017-02790-9 WOS000427248800003a.pdf 2041-1723 https://repositorio.unifesp.br/handle/11600/55823 WOS:000427248800003a |
url |
http://dx.doi.org/10.1038/s41467-017-02790-9 https://repositorio.unifesp.br/handle/11600/55823 |
identifier_str_mv |
Nature Communications. London, v. 9, 2018. 10.1038/s41467-017-02790-9 WOS000427248800003a.pdf 2041-1723 WOS:000427248800003a |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nature Communications |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
- application/pdf |
dc.coverage.none.fl_str_mv |
London |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
_version_ |
1814268429599768576 |