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...
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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) |
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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 |
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