Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes
Pítia Flores Ledur, Karina Karmirian, Carolina da S. G. Pedrosa, Letícia R. Q. Souza, Gabriela Lemos, Thiago Martino, Jéssica de Cassia Cavalheiro Gomes Ferreira, Gabriel Ferreira de Azevedo Reis, Eduardo dos Santos Silva, Débora Silva, José Alexandre Salerno, Isis M. Ornelas, Sylvie Devalle, Rodrigo Madeiro da Costa, Livia Goto‐Silva, Luiza M. Higa, Adriana Melo, Amílcar Tanuri, Leila Chimelli, Marcos Massao Murata, Patrícia P. Garcez, Eduardo Cremonese Filippi‐Chiela, Antônio Galina, Helena L. Borges, Stevens K. Rehen
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.