Coronaviruses exploit a host cysteine-aspartic protease for replication

Article

关键词: NUCLEOCAPSID PROTEIN;    ACTIVATION;    CASPASE-6;    SARS;    CLEAVAGE;    ENTRY;    4A;   

DOI  :  10.1038/s41586-022-05148-4

来源: SCIE

【 摘 要 】

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. (1,2)) (SARS-CoV-2), Middle East respiratory syndrome coronavirus(3) (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 culture(5-7) and in patient tissues(8-10), 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.

【 授权许可】

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