| Literature DB >> 35922005 |
Hin Chu1,2,3,4, Yuxin Hou5, Dong Yang5, Lei Wen5, Huiping Shuai5, Chaemin Yoon5, Jialu Shi5, Yue Chai5, Terrence Tsz-Tai Yuen5, Bingjie Hu5, Cun Li5, Xiaoyu Zhao5, Yixin Wang5, Xiner Huang5, Kin Shing Lee6, Cuiting Luo5, Jian-Piao Cai5, Vincent Kwok-Man Poon5,7, Chris Chung-Sing Chan5,7, Anna Jinxia Zhang8,5,9,7, Shuofeng Yuan8,5,9,7, Ko-Yung Sit10, Dominic Chi-Chung Foo10, Wing-Kuk Au10, Kenneth Kak-Yuen Wong10, Jie Zhou8,5,7, Kin-Hang Kok8,5,7, Dong-Yan Jin7,11,12, Jasper Fuk-Woo Chan13,14,15,16,17,18,19,20,21, Kwok-Yung Yuen22,23,24,25,26,27,28,29,30.
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.Entities:
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Year: 2022 PMID： 35922005 DOI： 10.1038/s41586-022-05148-4
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504