Abstract
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.
Highlights
Porcine epidemic diarrhea (PED) and its causative pathogen, porcine epidemic diarrhea virus (PEDV), were first recognized in Europe in the 1970s [1,2]
We found that the ORF3 protein enhanced the proliferation of PEDV by a mechanism most likely involving inhibition of apoptosis in infected cells
In the case of PEDV, studies about ORF3 protein have been incoherent; many involved gene sequence analyses but few were about its biological functions
Summary
Porcine epidemic diarrhea (PED) and its causative pathogen, porcine epidemic diarrhea virus (PEDV), were first recognized in Europe in the 1970s [1,2]. The disease spread to Asia in the 1980s and caused great economic losses to the pig industry in the area, especially after 2010 [3,4,5]. In 2013, the disease emerged and spread rapidly in North America, caused by a virus that most likely originated from Asia [6]. About 28 kb in length, encodes two nonstructural polyproteins (pp1a and pp1ab), four structural proteins—the approximately 200 kDa glycosylated spike (S) protein, 8 kDa envelope (E). Pp1a and pp1ab are the precursors of several enzymes and cofactors that together carry out PEDV genome replication and transcription. The N protein packages the genomic RNA to form the helical nucleocapsid (RNP)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.