State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
College of Animal Science, South China Agricultural University, Guangzhou, China.
Emerg Microbes Infect. 2020 Feb 24;9(1):439-456. doi: 10.1080/22221751.2020.1722758. eCollection 2020.
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 and . 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.
猪急性腹泻综合征冠状病毒（SADS-CoV）是一种新发现的肠道冠状病毒，是引起仔猪严重临床腹泻和肠道病理损伤的病原体。为了了解 SADS-CoV 对宿主细胞的影响，我们对其诱导细胞凋亡的途径进行了鉴定，并阐明了 SADS-CoV 感染后细胞凋亡的机制。SADS-CoV 感染的细胞表现出凋亡的证据， 和 。使用泛半胱天冬酶抑制剂导致 SADS-CoV 诱导的凋亡被抑制和 SADS-CoV 复制减少，提示 caspase 依赖性途径的关联。此外，SADS-CoV 感染激活了起始半胱天冬酶-8 和 -9，并上调 FasL 和 Bid 的切割，表明外源性和内源性途径之间存在串扰。然而，促凋亡蛋白 Bax 和 Cytochrome c（Cyt c）在 SADS-CoV 感染后分别向线粒体和细胞质重新定位。此外，用环孢菌素 A（CsA）处理的 Vero E6 和 IPI-2I 细胞，一种线粒体通透性转换孔（MPTP）开放的抑制剂，完全免受 SADS-CoV 诱导的凋亡和病毒复制的影响，表明亲环蛋白 D（CypD）参与了这些过程。总之，我们的结果表明 caspase 依赖性 FasL（外源性）和线粒体（内源性）介导的凋亡途径在 SADS-CoV 诱导的凋亡中起核心作用，促进了病毒复制。综上所述，这些发现表明了 SADS-CoV 诱导凋亡的机制，并提高了我们对 SADS-CoV 发病机制的理解。
