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

被引：28

作者：

Liu, Lihong ^{[1
,2
]}

Du, Jie ^{[1
]}

Yang, Sidi ^{[2
]}

Zheng, Birong ^{[1
,2
]}

Shen, Jian ^{[4
]}

Huang, Jiacheng ^{[2
]}

Cao, Liu ^{[1
]}

Huang, Siyao ^{[1
]}

Liu, Xue ^{[1
]}

Guo, Liping ^{[5
]}

Li, Chunmei ^{[1
]}

Ke, Changwen ^{[6
]}

Peng, Xiaofang ^{[6
]}

Guo, Deyin ^{[2
]}

Peng, Hong ^{[1
,3
]}

机构：

[1] Sun Yat Sen Univ, Sch Med, Ctr Infect & Immun Study CIIS, MOE Key Lab Trop Dis Control, Shenzhen Campus, Shenzhen, Peoples R China

[2] Guangzhou Lab, Guangzhou, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Sch Med, Shenzhen Key Lab Syst Med Inflammatory Dis, Shenzhen Campus, Shenzhen, Peoples R China

[4] Cent Hosp Panyu Dist, Dept Lab Med, Guangzhou, Peoples R China

[5] Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Hosp 2, Shenzhen, Guangdong, Peoples R China

[6] Guangdong Prov Ctr Dis Control & Prevent, Guangzhou, Guangdong, Peoples R China

来源：

REDOX BIOLOGY | 2023年 / 63卷

基金：

中国国家自然科学基金;

关键词：

SARS-CoV-2; ORF3a; Ferroptosis; Keap1; NRF2; DEATH; INFECTION; RESPONSES; NRF2;

D O I：

10.1016/j.redox.2023.102752

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：15

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