Coronaviruses exploit a host cysteine-aspartic protease for replication.
Nature
; 609(7928): 785-792, 2022 09.
Article
in English
| MEDLINE | ID: covidwho-1972633
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Replication
/
Aspartic Acid
/
Coronavirus Infections
/
Coronavirus
/
Cysteine
/
Caspase 6
/
Host-Pathogen Interactions
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Nature
Year:
2022
Document Type:
Article
Affiliation country:
S41586-022-05148-4
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