Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity.
Sci Adv
; 7(25)2021 06.
Article
in English
| MEDLINE | ID: covidwho-1276873
ABSTRACT
Infection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R-like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2- and SARS-CoV-induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2-inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Apoptosis
/
Coronavirus Infections
/
EIF-2 Kinase
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Sciadv.abf8577
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