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.

Transmissible gastroenteritis virus (TGEV) is an infective coronavirus (CoV) that causes diarrhea-related morbidity and mortality in piglets. For the first time, a natural recombination strain of a TGEV Anhui Hefei (AHHF) virus between the Purdue and the Miller clusters was isolated from the small intestine content of piglets in China. A phylogenetic tree based on a complete genome sequence placed the TGEV AHHF strain between the Purdue and the Miller clusters. The results of a computational analysis of recombination showed that the TGEV AHHF strain is a natural recombinant strain between these clusters. Two breakpoints located in the open reading frame 1a (ORF1a) and spike (S) genes were identified. The pathogenicity of the TGEV AHHF strain was evaluated in piglets, and the results show that TGEV AHHF is an enteric pathogenic strain. These results provide valuable information about the recombination and evolution of CoVs and will facilitate future investigations of the molecular pathogenesis of TGEV.

No abstract