SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis

Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-...

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Detalles Bibliográficos
Autores principales: Liu, Lihong, Du, Jie, Yang, Sidi, Zheng, Birong, Shen, Jian, Huang, Jiacheng, Cao, Liu, Huang, Siyao, Liu, Xue, Guo, Liping, Li, Chunmei, Ke, Changwen, Peng, Xiaofang, Guo, Deyin, Peng, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202901/
https://www.ncbi.nlm.nih.gov/pubmed/37245288
http://dx.doi.org/10.1016/j.redox.2023.102752
Descripción
Sumario:Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced cell death. Previous studies have observed enhanced ROS level and signs of ferroptosis in SARS-CoV-2 infected cells or specimens of patients with COVID-19, but the exact mechanism is not clear yet. Here, we find SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis. SARS-CoV-2 ORF3a promotes the degradation of NRF2 through recruiting Keap1, thereby attenuating cellular resistance to oxidative stress and facilitated cells to ferroptotic cell death. Our study uncovers that SARS-CoV-2 ORF3a functions as a positive regulator of ferroptosis, which might explain SARS-CoV-2-induced damage in multiple organs in COVID-19 patients and imply the potential of ferroptosis inhibition in COVID-19 treatment.

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