학술논문
Coronaviruses exploit a host cysteine-aspartic protease for replication
Document Type
Original Paper
Author
Chu, Hin; Hou, Yuxin; Yang, Dong; Wen, Lei; Shuai, Huiping; Yoon, Chaemin; Shi, Jialu; Chai, Yue; Yuen, Terrence Tsz-Tai; Hu, Bingjie; Li, Cun; Zhao, Xiaoyu; Wang, Yixin; Huang, Xiner; Lee, Kin Shing; Luo, Cuiting; Cai, Jian-Piao; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Zhang, Anna Jinxia; Yuan, Shuofeng; Sit, Ko-Yung; Foo, Dominic Chi-Chung; Au, Wing-Kuk; Wong, Kenneth Kak-Yuen; Zhou, Jie; Kok, Kin-Hang; Jin, Dong-Yan; Chan, Jasper Fuk-Woo; Yuen, Kwok-Yung
Source
Nature: International weekly journal of science. 609(7928):785-792
Subject
Language
English
ISSN
0028-0836
1476-4687
1476-4687
Abstract
Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2 ) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3 (MERS-CoV) and SARS-CoV-1 (ref. 4 ), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5–7 and in patient tissues8–10 , suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.
Coronaviruses exploit the host caspase-6 to cleave coronavirus nucleocapsid protein into fragments with interferon-antagonizing activity to facilitate virus replication.
Coronaviruses exploit the host caspase-6 to cleave coronavirus nucleocapsid protein into fragments with interferon-antagonizing activity to facilitate virus replication.