Copper imbalance linked to oxidative stress and cell death during Zika virus infection in human astrocytes

Author:

Puig-Pijuan Teresa,Souza Leticia R. Q.,Pedrosa Carolina da S. G.,Higa Luiza M.,Monteiro Fabio Luis,Tanuri Amilcar,Valverde Rafael H. F.,Einicker-Lamas Marcelo,Rehen Stevens Kastrup

Abstract

AbstractThe Zika virus (ZIKV) caused neurological abnormalities in more than 3500 Brazilian newborns between 2015 and 2020. 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. For this reason, we investigated copper homeostasis imbalance as a factor that could contribute to the cytotoxic effects of ZIKV infection in iPSC-derived human astrocytes. Our results show that 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-mediated copper sequestration in ZIKV-infected 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.

Publisher

Cold Spring Harbor Laboratory

Reference59 articles.

1. Zika Virus (I). Isolations and serological specificity

2. Ministério da Saúde (BR), “Situação epidemiológica da síndrome congênita associada à infecção pelo vírus Zika, 2015 a 2020,” Boletim epidemiológico 52, Feb. 2021. Accessed: Dec. 21, 2021. [Online]. Available: http://www.saude.gov.br/boletins-epidemiologicos

3. Ministério da Saúde, “Monitoramento dos casos de arboviroses urbanas causados por vírus transmitidos pelo mosquito Aedes (dengue, chikungunya e zika), semanas epidemiológicas 1 a 29, 2021” Brasil, Boletim epidemiológico 52, Jul. 2021. Accessed: Dec. 21, 2021. [Online]. Available: http://www.saude.gov.br/boletins-epidemiologicos

4. The Brazilian Zika virus strain causes birth defects in experimental models

5. Zika virus impairs growth in human neurospheres and brain organoids

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3