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Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Enhances Viral Proliferation by Inhibiting Apoptosis of Infected Cells

by Fusheng Si 1,2,†, Xiaoxia Hu 1,2,†, Chenyang Wang 1,3, Bingqing Chen 1,2, Ruiyang Wang 1,2, Shijuan Dong 1,2, Ruisong Yu 1,2 and Zhen Li 1,2,*
1
Institute of Animal Science and Veterinary Medicine, Shanghai Key Laboratory of Agricultural Genetics and Breeding, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
2
Shanghai Engineering Research Center of Breeding Pig, Shanghai 201106, China
3
National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2020, 12(2), 214; https://doi.org/10.3390/v12020214
Received: 28 December 2019 / Revised: 11 February 2020 / Accepted: 13 February 2020 / Published: 14 February 2020
(This article belongs to the Section Animal Viruses)
The genomes of coronaviruses carry accessory genes known to be associated with viral virulence. The single accessory gene of porcine epidemic diarrhea virus (PEDV), ORF3, is dispensable for virus replication in vitro, while viral mutants carrying ORF3 truncations exhibit an attenuated phenotype of which the underlying mechanism is unknown. Here, we studied the effect of ORF3 deletion on the proliferation of PEDV in Vero cells. To this end, four recombinant porcine epidemic diarrhea viruses (PEDVs) were rescued using targeted RNA recombination, three carrying the full-length ORF3 gene from different PEDV strains, and one from which the ORF3 gene had been deleted entirely. Our results showed that PEDVs with intact or naturally truncated ORF3 replicated to significantly higher titers than PEDV without an ORF3. Further characterization revealed that the extent of apoptosis induced by PEDV infection was significantly lower with the viruses carrying an intact or C-terminally truncated ORF3 than with the virus lacking ORF3, indicating that the ORF3 protein as well as its truncated form interfered with the apoptosis process. Collectively, we conclude that PEDV ORF3 protein promotes virus proliferation by inhibiting cell apoptosis caused by virus infection. Our findings provide important insight into the role of ORF3 protein in the pathogenicity of PEDV. View Full-Text
Keywords: PEDV; the role of ORF3; proliferation; apoptosis; cells PEDV; the role of ORF3; proliferation; apoptosis; cells
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Si, F.; Hu, X.; Wang, C.; Chen, B.; Wang, R.; Dong, S.; Yu, R.; Li, Z. Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Enhances Viral Proliferation by Inhibiting Apoptosis of Infected Cells. Viruses 2020, 12, 214.

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