Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent

ABSTRACTSwine 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 pathw...

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Main Authors: Jiyu Zhang, Yuru Han, Hongyan Shi, Jianfei Chen, Xin Zhang, Xiaobo Wang, Ling Zhou, Jianbo Liu, Jialin Zhang, Zhaoyang Ji, Zhaoyang Jing, Jingyun Ma, Da Shi, Li Feng
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1722758
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author Jiyu Zhang
Yuru Han
Hongyan Shi
Jianfei Chen
Xin Zhang
Xiaobo Wang
Ling Zhou
Jianbo Liu
Jialin Zhang
Zhaoyang Ji
Zhaoyang Jing
Jingyun Ma
Da Shi
Li Feng
author_facet Jiyu Zhang
Yuru Han
Hongyan Shi
Jianfei Chen
Xin Zhang
Xiaobo Wang
Ling Zhou
Jianbo Liu
Jialin Zhang
Zhaoyang Ji
Zhaoyang Jing
Jingyun Ma
Da Shi
Li Feng
author_sort Jiyu Zhang
collection DOAJ
description ABSTRACTSwine 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.
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spelling doaj.art-6b35c2483e334d42b6e5ae4b2343adcc2024-03-11T16:04:24ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-019143945610.1080/22221751.2020.1722758Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependentJiyu Zhang0Yuru Han1Hongyan Shi2Jianfei Chen3Xin Zhang4Xiaobo Wang5Ling Zhou6Jianbo Liu7Jialin Zhang8Zhaoyang Ji9Zhaoyang Jing10Jingyun Ma11Da Shi12Li Feng13State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaCollege of Animal Science, South China Agricultural University, Guangzhou, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaCollege of Animal Science, South China Agricultural University, Guangzhou, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, ChinaABSTRACTSwine 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.https://www.tandfonline.com/doi/10.1080/22221751.2020.1722758SADS-CoVapoptosisapoptosis-inducing factorpathogenesis
spellingShingle Jiyu Zhang
Yuru Han
Hongyan Shi
Jianfei Chen
Xin Zhang
Xiaobo Wang
Ling Zhou
Jianbo Liu
Jialin Zhang
Zhaoyang Ji
Zhaoyang Jing
Jingyun Ma
Da Shi
Li Feng
Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent
Emerging Microbes and Infections
SADS-CoV
apoptosis
apoptosis-inducing factor
pathogenesis
title Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent
title_full Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent
title_fullStr Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent
title_full_unstemmed Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent
title_short Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent
title_sort swine acute diarrhea syndrome coronavirus induced apoptosis is caspase and cyclophilin d dependent
topic SADS-CoV
apoptosis
apoptosis-inducing factor
pathogenesis
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1722758
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