内质网
未折叠蛋白反应
细胞生物学
二硫键
化学
降级(电信)
寄主(生物学)
生物
生物化学
生态学
电信
计算机科学
作者
Ping Liu,Xi Wang,Yiwei Sun,Hongyu Zhao,Fang Cheng,Jifeng Wang,Fuchao Yang,Junjie Hu,Hong Zhao,Chih-chen Wang,Lei Wang
出处
期刊:Redox biology
[Elsevier]
日期:2022-08-01
卷期号:54: 102388-102388
被引量:17
标识
DOI:10.1016/j.redox.2022.102388
摘要
The replication machinery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is closely associated with the endoplasmic reticulum (ER) in host cells. Activation of the unfolded protein response (UPR) is a strategy hijacked by coronavirus to facilitate its replication and suppress host innate immunity. Here, we have found that SARS-CoV-2 ORF8 protein accumulates in the ER and escapes the degradation system by forming mixed disulfide complexes with ER oxidoreductases. ORF8 induces the activation of three UPR pathways through targeting key UPR components, remodels ER morphology and accelerates protein trafficking. Moreover, small molecule reducing agents release ORF8 from the mixed disulfide complexes and facilitate its degradation, therefore mitigate ER stress. Our study reveals a unique mechanism by which SARS-CoV-2 ORF8 escapes degradation by host cells and regulates ER reshaping. Targeting ORF8-involved mixed disulfide complexes could be a new strategy to alleviate SARS-CoV-2 induced ER stress and related diseases.
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