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Data have pointed to oxidative stress in astrocytes as well as to dysregulations in neural cell proliferation and cell cycle as important events accounting for the cell death and neurological complications observed in Congenital Zika Syndrome. Copper imbalance has been shown to induce similar alterations in other pathologies, and disturbances in copper homeostasis have already been described in viral infections. Here, we investigated copper homeostasis imbalance as a factor that could contribute to the cytotoxic effects of ZIKV infection in astrocytes. Human\u00a0induced pluripotent stem cell\u2010derived astrocytes were infected with ZIKV; changes in the gene expression of copper homeostasis proteins were analyzed. The effect of the administration of CuCl<jats:sub>2<\/jats:sub> or a copper chelator on oxidative stress, cell viability and percentage of infection were also studied. ZIKV infection leads to a downregulation of one of the transporters mediating copper release, ATP7B protein. We also observed the activation of mechanisms that counteract high copper levels, including the synthesis of copper chaperones and the reduction of the copper importer protein CTR1. Finally, we show that chelator\u2010mediated copper sequestration in ZIKV\u2010infected astrocytes reduces the levels of reactive oxygen species and improves cell viability, but does not change the overall percentage of infected cells. In summary, our results show that copper homeostasis imbalance plays a role in the pathology of ZIKV in astrocytes, indicating that it may also be a factor accounting for the developmental abnormalities in the central nervous system following viral infection. Evaluating micronutrient levels and the use of copper chelators in pregnant women susceptible to ZIKV infection may be promising strategies to manage novel cases of congenital ZIKV syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.30323","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T19:00:59Z","timestamp":1662404459000},"page":"1997-2008","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Copper regulation disturbance linked to oxidative stress and cell death during Zika virus infection in human astrocytes"],"prefix":"10.1002","volume":"123","author":[{"given":"Teresa","family":"Puig\u2010Pijuan","sequence":"first","affiliation":[{"name":"D'Or Institute for Research and Education (IDOR) Rio de Janeiro Brazil"},{"name":"Laboratory of Biomembranes, Carlos Chagas Filho Biophysics Institute Federal University of Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia R. 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