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.
【저자키워드】 Apoptosis, Pathogenesis, SADS-CoV, apoptosis-inducing factor, 【초록키워드】 coronavirus, Infection, in vitro, diarrhea, Replication, Protein, viral replication, pathway, cleavage, in vivo, inhibitor, mechanism, association, cyclosporin A, Evidence, Pathways, Vero E6, mitochondrial, cytoplasm, host cells, apoptotic pathway, acute diarrhea, caspase-8, syndrome, Cell, Apoptotic cell death, cytochrome, IMPROVE, intrinsic, facilitate, characterized, treated, activated, induce, cause, upregulated, reduction in, extrinsic, Bax, intestinal pathological damage, MPTP, 【제목키워드】 caspase, acute diarrhea, syndrome,