Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent.
Emerg Microbes Infect
; 9(1): 439-456, 2020.
Article
in English
| MEDLINE | ID: covidwho-124861
ABSTRACT
Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly discovered enteric coronavirus, is the aetiological agent that causes severe clinical diarrhea and intestinal pathological damage in piglets. To understand the effect of SADS-CoV on host cells, we characterized the apoptotic pathways and elucidated mechanisms underlying the process of apoptotic cell death after SADS-CoV infection. SADS-CoV-infected cells showed evidence of apoptosis in vitro and in vivo. The use of a pan-caspase inhibitor resulted in the inhibition of SADS-CoV-induced apoptosis and reduction in SADS-CoV replication, suggestive of the association of a caspase-dependent pathway. Furthermore, SADS-CoV infection activated the initiators caspase-8 and -9 and upregulated FasL and Bid cleavage, demonstrating a crosstalk between the extrinsic and intrinsic pathways. However, the proapoptotic proteins Bax and Cytochrome c (Cyt c) relocalized to the mitochondria and cytoplasm, respectively, after infection by SADS-CoV. Moreover, Vero E6 and IPI-2I cells treated with cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPTP) opening, were completely protected from SADS-CoV-induced apoptosis and viral replication, suggesting the involvement of cyclophilin D (CypD) in these processes. Altogether, our results indicate that caspase-dependent FasL (extrinsic)- and mitochondria (intrinsic)- mediated apoptotic pathways play a central role in SADS-CoV-induced apoptosis that facilitates viral replication. In summary, these findings demonstrate mechanisms by which SADS-CoV induces apoptosis and improve our understanding of SADS-CoV pathogenesis.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Apoptosis
/
Coronavirus Infections
/
Caspases
/
Alphacoronavirus
/
Cyclophilin D
Type of study:
Etiology study
/
Prognostic study
Limits:
Animals
Language:
English
Journal:
Emerg Microbes Infect
Year:
2020
Document Type:
Article
Affiliation country:
22221751.2020.1722758
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