Porcine epidemic diarrhea virus ORF3 gene prolongs S-phase, facilitates formation of vesicles and promotes the proliferation of attenuated PEDV

Ye, Shiyi; Li, Zhonghua; Chen, Fangzhou; Li, Wentao; Hu, Han; He, Qigai

doi:10.1007/s11262-015-1257-y

Cited by 43 publications

(57 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Porcine epidemic diarrhea virus (PEDV), the causative agent of PED, is an enveloped, positive-stranded RNA virus in the genus Alphacoronavirus, family Coronaviridae, order Nidovirales (Sato et al, 2018;Yu et al, 2018). The genome of a PEDV is approximately 28 k nt in length and is composed of seven open reading frames (ORFs) arranging in the order 5′-ORF1a/1b-S-ORF3-E-M-N-3′, which encodes four structural proteins and seventeen non-structural proteins (nsp1-nsp16, and ORF3) (Ye et al, 2015;Cheun-Arom et al, 2016). The 5′ two thirds of the genome contains two overlapping ORFs, ORF1a and ORF1b, which encode nsps that are cleaved by viral encoded proteases into 16 nsps (nsp1-16), directing genome replication, transcription, translation and viral polyprotein processing (Huang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, ORF3, as the only accessory gene in PEDV, is thought to function as an ion channel and to influence virus production and virulence (Wang et al, 2012). PEDV ORF3 protein can prolong cellular S-phase, facilitate formation of vesicles and thus promote the proliferation of attenuated PEDV rather than virulent PEDV (Ye et al, 2015). Previous study demonstrated that ORF3 and S are co-localized in several cellular compartments in infected cells, and ORF3 may interact with S during PEDV assembly and consequently exert its activity at this step of virus replication (Kaewborisuth et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Porcine epidemic diarrhea virus ORF3 protein causes endoplasmic reticulum stress to facilitate autophagy

Zou

Duan

et al. 2019

Veterinary Microbiology

View full text Add to dashboard Cite

A B S T R A C TPorcine epidemic diarrhea virus (PEDV), the causative agent of PED, is an enveloped, positive-stranded RNA virus in the genus Alphacoronavirus, family Coronaviridae, order Nidovirales. PEDV non-structural accessory protein ORF3 is an ion channel related to viral infectivity and pathogenicity. Our previous study showed that PEDV ORF3 has expression characteristic of aggregation in cytoplasm, but its biological function remains elusive. Thus in this study, we initiated the construction of various vectors to express ORF3, and found ORF3 localized in the cytoplasm in the aggregation manner. Subsequently, confocal microscopy analysis showed that the aggregated ORF3 localized in endoplasmic reticulum (ER) to trigger ER stress response via up-regulation of GRP78 protein expression and activation of PERK-eIF2α signaling pathway. In addition, our results showed that PEDV ORF3 could induce the autophagy through inducing conversion of LC3-I to LC3-II, but couldn't influence the apoptosis. In contrast, conversion of LC3-I/LC3-II could be significantly inhibited by 4-PBA, an ER stress inhibitor, indicating that ORF3-induced autophagy is dependent on ER stress response. This work not only provides some new findings for the biological function of the PEDV ORF3 protein, but also help us for the further understanding the molecular interaction between PEDV ORF3 protein and cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Porcine epidemic diarrhea virus ORF3 protein causes endoplasmic reticulum stress to facilitate autophagy

Zou

Duan

et al. 2019

Veterinary Microbiology

View full text Add to dashboard Cite

show abstract

“…The PEDV S protein is a key factor that mediates the entry of PEDV into host cells by binding to aminopeptidase N and/or glycan receptors through an unknown mechanism, thereby initiating the fusion of the virus envelope with the host cell membrane and the subsequent infection cycle (He et al, 2005;Ye et al, 2015). Thus, the S glycoprotein is the primary target for the development of vaccines against PEDV, as well as for understanding the genetic relationships between different strains and the epidemiological status of PEDV in the field.…”

Section: Introductionmentioning

confidence: 99%

“…Unlike the structural proteins, little is known about the functions of the accessory proteins. The ORF3 gene, which is the only accessory gene, encodes an ion channel protein that regulates virus production , and it has been suggested to be an important virulence determinant (Ye et al, 2015). A previous report suggested that piglets that were inoculated orally with the wild-type CV777 strain became sick and developed severe diarrhea.…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of Chinese porcine epidemic diarrhea virus with novel mutations and deletions in the S gene

Sun

Shao

et al. 2018

Veterinary Microbiology

View full text Add to dashboard Cite

Porcine epidemic diarrhea (PEDV) has raised growing concerns in the pig-breeding industry because it has caused significant economic losses. To better understand the molecular epidemiology and genetic diversity of PEDV field isolates, in this study, the complete spike (S) and ORF3 genes of 17 PEDV variants in Zhejiang, China during 2014 to 2017, were characterized and analyzed. Phylogenetic analysis based on the S gene and ORF3 gene of these 17 novel PEDV strains and PEDV reference strains indicated that all the PEDV strains fell into two groups designated G1 and G2. Notably, the strains identified in 2014-2015 were in G2, while the other five strains identified from 2016 to 2017 were in G1. Sequencing and phylogenetic analyses showed that recently prevalent Chinese PEDV field strains shared higher identities with United States strains than with South Korean strains. Compared with classical vaccine strains, a series of deletions and frequently occurring mutations were observed in the receptor binding domains of our PEDV strains. Besides, we successfully isolated and reported the genetic characterization two novel PEDV strains, PEDV-LA1 and PEDV-LY4-98, found on the Chinese mainland, which had significant variations in the S gene. Meanwhile, the virulence of the new mutants may be changed, the PEDV-LY4-98 strain, which has multiple mutations in the signal peptide-encoding fragment of the S gene showed delayed cytopathic effects and smaller plaque size compared with strain PEDV-LA1, which lacks these mutations. Three unique amino acid substitutions (L7, G8, and V9) were identified in the SP-encoding fragment of the S1 N-terminal domain of the PEDV-LY4-98 S protein compared with the S proteins of all the previous PEDV strains. The animal experiment revealed that these two novel strains were high pathogenic to neonatal pigs. Whether these amino acids substitutions and the N-glycosylation site substitutions influence the antigenicity and pathogenicity of PEDV remains to be investigated. Meanwhile, amino acid substitutions in the neutralizing epitopes may have conferred the capacity for immune evasion in these PEDV field strains. This study improves our understanding of ongoing PEDV outbreaks in China, and it will guide further efforts to develop effective measures to control this virus.

show abstract

“…ORF3 encoded genes are not required for CoV growth in cell culture, although virus yield could be increased in their presence (Ye et al, 2015; Zhang et al, 2014b). A common feature between HCoV-229E, TGEV and PEDV is that cell-adapted strains tend to modify ORF3 (Fig.…”

Section: Viral Proteins As Virulence Factorsmentioning

confidence: 99%

Virulence factors in porcine coronaviruses and vaccine design

et al. 2016

View full text Add to dashboard Cite

Porcine enteric coronaviruses (CoVs) cause severe disease in the porcine herds worldwide, leading to important economic losses. Despite the knowledge of these viruses since the 1970’s, vaccination strategies have not been implemented, leading to continuous re-emergence of novel virulent strains. Live attenuated vaccines historically have been the most efficient. We consider that the new trend is the development of recombinant vaccines by using reverse genetics systems to engineer attenuated viruses, which could be used as effective and safe modified live vaccine candidates. To this end, host cell signaling pathways influencing porcine CoV virulence should be identified. Similarly, the identity of viral proteins involved in the modulation of host cell pathways influencing CoV pathogenesis should be analyzed. With this information, and using reverse genetics systems, it is possible to design viruses with modifications in the viral proteins acting as virulence factors, which may lead to attenuated viruses and, therefore, vaccine candidates. In addition, novel antiviral drugs may be developed once the host cell pathways and the molecular mechanism affecting porcine CoV replication and virulence are known. This review is focused in the host cell responses to enteric porcine CoV infection and the viral proteins involved in pathogenesis.

show abstract

Porcine epidemic diarrhea virus ORF3 gene prolongs S-phase, facilitates formation of vesicles and promotes the proliferation of attenuated PEDV

Cited by 43 publications

References 43 publications

Porcine epidemic diarrhea virus ORF3 protein causes endoplasmic reticulum stress to facilitate autophagy

Porcine epidemic diarrhea virus ORF3 protein causes endoplasmic reticulum stress to facilitate autophagy

Isolation and characterization of Chinese porcine epidemic diarrhea virus with novel mutations and deletions in the S gene

Virulence factors in porcine coronaviruses and vaccine design

Contact Info

Product

Resources

About