Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes

Abstract Zika virus (ZIKV) has been extensively studied since it was linked to congenital malformations, and recent research has revealed that astrocytes are targets of ZIKV. However, the consequences of ZIKV infection, especially to this cell type, remain largely unknown, particularly considering i...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Pítia Flores Ledur, Karina Karmirian, Carolina da Silva Gouveia Pedrosa, Leticia Rocha Quintino Souza, Gabriela Assis-de-Lemos, Thiago Martino Martins, Jéssica de Cassia Cavalheiro Gomes Ferreira, Gabriel Ferreira de Azevedo Reis, Eduardo Santos Silva, Débora Silva, José Alexandre Salerno, Isis Moraes Ornelas, Sylvie Devalle, Rodrigo Furtado Madeiro da Costa, Livia Goto-Silva, Luiza Mendonça Higa, Adriana Melo, Amilcar Tanuri, Leila Chimelli, Marcos Massao Murata, Patrícia Pestana Garcez, Eduardo Cremonese Filippi-Chiela, Antonio Galina, Helena Lobo Borges, Stevens Kastrup Rehen
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2020
Materias:
R
Q
Acceso en línea:https://doaj.org/article/9e62ed1ee57742299fe776937168f5bf
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:9e62ed1ee57742299fe776937168f5bf
record_format dspace
spelling oai:doaj.org-article:9e62ed1ee57742299fe776937168f5bf2021-12-02T14:16:42ZZika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes10.1038/s41598-020-57914-x2045-2322https://doaj.org/article/9e62ed1ee57742299fe776937168f5bf2020-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-57914-xhttps://doaj.org/toc/2045-2322Abstract Zika virus (ZIKV) has been extensively studied since it was linked to congenital malformations, and recent research has revealed that astrocytes are targets of ZIKV. However, the consequences of ZIKV infection, especially to this cell type, remain largely unknown, particularly considering integrative studies aiming to understand the crosstalk among key cellular mechanisms and fates involved in the neurotoxicity of the virus. Here, the consequences of ZIKV infection in iPSC-derived astrocytes are presented. Our results show ROS imbalance, mitochondrial defects and DNA breakage, which have been previously linked to neurological disorders. We have also detected glial reactivity, also present in mice and in post-mortem brains from infected neonates from the Northeast of Brazil. Given the role of glia in the developing brain, these findings may help to explain the observed effects in congenital Zika syndrome related to neuronal loss and motor deficit.Pítia Flores LedurKarina KarmirianCarolina da Silva Gouveia PedrosaLeticia Rocha Quintino SouzaGabriela Assis-de-LemosThiago Martino MartinsJéssica de Cassia Cavalheiro Gomes FerreiraGabriel Ferreira de Azevedo ReisEduardo Santos SilvaDébora SilvaJosé Alexandre SalernoIsis Moraes OrnelasSylvie DevalleRodrigo Furtado Madeiro da CostaLivia Goto-SilvaLuiza Mendonça HigaAdriana MeloAmilcar TanuriLeila ChimelliMarcos Massao MurataPatrícia Pestana GarcezEduardo Cremonese Filippi-ChielaAntonio GalinaHelena Lobo BorgesStevens Kastrup RehenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Pítia Flores Ledur
Karina Karmirian
Carolina da Silva Gouveia Pedrosa
Leticia Rocha Quintino Souza
Gabriela Assis-de-Lemos
Thiago Martino Martins
Jéssica de Cassia Cavalheiro Gomes Ferreira
Gabriel Ferreira de Azevedo Reis
Eduardo Santos Silva
Débora Silva
José Alexandre Salerno
Isis Moraes Ornelas
Sylvie Devalle
Rodrigo Furtado Madeiro da Costa
Livia Goto-Silva
Luiza Mendonça Higa
Adriana Melo
Amilcar Tanuri
Leila Chimelli
Marcos Massao Murata
Patrícia Pestana Garcez
Eduardo Cremonese Filippi-Chiela
Antonio Galina
Helena Lobo Borges
Stevens Kastrup Rehen
Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes
description Abstract Zika virus (ZIKV) has been extensively studied since it was linked to congenital malformations, and recent research has revealed that astrocytes are targets of ZIKV. However, the consequences of ZIKV infection, especially to this cell type, remain largely unknown, particularly considering integrative studies aiming to understand the crosstalk among key cellular mechanisms and fates involved in the neurotoxicity of the virus. Here, the consequences of ZIKV infection in iPSC-derived astrocytes are presented. Our results show ROS imbalance, mitochondrial defects and DNA breakage, which have been previously linked to neurological disorders. We have also detected glial reactivity, also present in mice and in post-mortem brains from infected neonates from the Northeast of Brazil. Given the role of glia in the developing brain, these findings may help to explain the observed effects in congenital Zika syndrome related to neuronal loss and motor deficit.
format article
author Pítia Flores Ledur
Karina Karmirian
Carolina da Silva Gouveia Pedrosa
Leticia Rocha Quintino Souza
Gabriela Assis-de-Lemos
Thiago Martino Martins
Jéssica de Cassia Cavalheiro Gomes Ferreira
Gabriel Ferreira de Azevedo Reis
Eduardo Santos Silva
Débora Silva
José Alexandre Salerno
Isis Moraes Ornelas
Sylvie Devalle
Rodrigo Furtado Madeiro da Costa
Livia Goto-Silva
Luiza Mendonça Higa
Adriana Melo
Amilcar Tanuri
Leila Chimelli
Marcos Massao Murata
Patrícia Pestana Garcez
Eduardo Cremonese Filippi-Chiela
Antonio Galina
Helena Lobo Borges
Stevens Kastrup Rehen
author_facet Pítia Flores Ledur
Karina Karmirian
Carolina da Silva Gouveia Pedrosa
Leticia Rocha Quintino Souza
Gabriela Assis-de-Lemos
Thiago Martino Martins
Jéssica de Cassia Cavalheiro Gomes Ferreira
Gabriel Ferreira de Azevedo Reis
Eduardo Santos Silva
Débora Silva
José Alexandre Salerno
Isis Moraes Ornelas
Sylvie Devalle
Rodrigo Furtado Madeiro da Costa
Livia Goto-Silva
Luiza Mendonça Higa
Adriana Melo
Amilcar Tanuri
Leila Chimelli
Marcos Massao Murata
Patrícia Pestana Garcez
Eduardo Cremonese Filippi-Chiela
Antonio Galina
Helena Lobo Borges
Stevens Kastrup Rehen
author_sort Pítia Flores Ledur
title Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes
title_short Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes
title_full Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes
title_fullStr Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes
title_full_unstemmed Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes
title_sort zika virus infection leads to mitochondrial failure, oxidative stress and dna damage in human ipsc-derived astrocytes
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/9e62ed1ee57742299fe776937168f5bf
work_keys_str_mv AT pitiafloresledur zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT karinakarmirian zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT carolinadasilvagouveiapedrosa zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT leticiarochaquintinosouza zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT gabrielaassisdelemos zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT thiagomartinomartins zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT jessicadecassiacavalheirogomesferreira zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT gabrielferreiradeazevedoreis zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT eduardosantossilva zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT deborasilva zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT josealexandresalerno zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT isismoraesornelas zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT sylviedevalle zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT rodrigofurtadomadeirodacosta zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT liviagotosilva zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT luizamendoncahiga zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT adrianamelo zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT amilcartanuri zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT leilachimelli zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT marcosmassaomurata zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT patriciapestanagarcez zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT eduardocremonesefilippichiela zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT antoniogalina zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT helenaloboborges zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
AT stevenskastruprehen zikavirusinfectionleadstomitochondrialfailureoxidativestressanddnadamageinhumanipscderivedastrocytes
_version_ 1718391683173842944