Emergence and evolution of highly pathogenic porcine epidemic diarrhea virus by natural recombination of a low pathogenic vaccine isolate and a highly pathogenic strain in the spike gene

Abstract

<jats:title>Abstract</jats:title> <jats:p>Outbreaks of a new variant of porcine epidemic diarrhea virus (PEDV) at the end of 2010 have raised interest in the mutation and recombination of PEDV. A PEDV strain (CN/Liaoning25/2018) isolated from a clinical outbreak of piglet diarrhea contained a 49 bp deletion in the ORF3 gene. This deletion is considered a genetic characteristic of low pathogenic attenuated vaccine strains. However, CN/Liaoning25/2018 was highly pathogenic. Complete genome sequencing, identity analysis, phylogenetic tree construction, and recombination analysis showed that this virus was a recombinant strain containing the Spike (S) gene from the highly pathogenic CN/GDZQ/2014 strain and the remaining genomic regions from the low pathogenic vaccine isolate SQ2014. Histopathology and immunohistochemistry results confirmed that this strain was highly pathogenic and indicated that intestinal epithelial cell vacuolation was positively correlated with the intensity and density of PEDV antigens. A new natural recombination model for PEDV was identified. Our results suggest that new highly pathogenic recombinant strains in the field may be generated by recombination between low pathogenic attenuated live PEDV vaccines and pathogenic circulating PEDV strains. Our findings also highlight that the 49 bp deletion of the ORF3 gene in low pathogenic attenuated vaccine strains will no longer be a reliable standard to differentiate the classical vaccine attenuated from the field strains.</jats:p>

Drawing Comparisons between SARS-CoV-2 and the Animal Coronaviruses

“…The development of an effective and safe vaccine against SARS-CoV-2 is of paramount importance. Although there are no licensed vaccines against CoVs in humans so far, the various issues (lack of complete protection, short duration of immunity, correlates of protection against CoVs, emergence of multiple serotypes/subtypes including virulent recombinants between vaccine and field strains, and/or ADE enhanced disease) observed with the veterinary CoV vaccines should be taken into consideration while devising immunization strategies against SARS-CoV-2 [ 17 , 18 , 22 , 30 , 32 , 33 , 254 , 255 ].…”

“…Although the currently licensed animal CoV vaccines appeared to reduce mortality/viral shedding, none seem to offer complete protection [ 33 ]. Other concerns associated with the animal CoV vaccines included a relatively short duration of protective immunity, lack of a clear understanding of the correlates of protection against CoVs, emergence of multiple serotypes/subtypes that influence vaccine efficacy, and/or ADE enhanced disease [ 14 , 17 , 18 , 22 , 30 , 32 , 33 , 254 , 255 ].…”

“…Because of high strain diversity between countries/regions, the attenuated viruses used in the current IBV vaccines vary depending on the geographical location (M41 (Massachusetts), Arkansas and Connecticut in North America, 4/91 and D274 in Europe, and QX in China). Similar to IBV, recombination events including a recent report on recombination between a highly pathogenic field PEDV strain and a low pathogenic attenuated vaccine PEDV strain have been found to negatively impact the efficacy of the current PEDV vaccines [ 18 , 32 , 255 ]. On the other hand, genetic diversity in the CoV genome has also resulted in the emergence of naturally attenuated viruses that offer protection against the virulent counterparts, such as PRCoV (deletion mutant of TGEV, causes mild respiratory disease), which has been attributed to the worldwide reduction in outbreaks of severe gastroenteritis with TGEV [ 20 , 153 ].…”

The spike glycoprotein genes of porcine epidemic diarrhea viruses isolated in China

“…This recombination occurred not only in structural protein-coding region (S and N genes) but also in non-structural protein-coding region (pp1a gene and ORF3) [ 48 ]. PEDV TCN/Liaoning25/2018 (GenBank: MK796238.1) was another natural recombinant strain that contains the S gene from the highly pathogenic CH/GDZQ/2014 strain (GenBank:KM242131.1) and the remaining genomic regions from the low pathogenic vaccine isolate SQ2014 (GenBank: KP728470.1) [ 49 ].…”

Study on the Characteristic Codon Usage Pattern in Porcine Epidemic Diarrhea Virus Genomes and Its Host Adaptation Phenotype

“…The only accessory protein ORF3 has ion channel activity ( Wang et al, 2012 ), and was found beneficial to virus proliferation ( Wang et al, 2012 ; Ye et al, 2015 ; Si et al, 2020 ). Phylogenetic analysis showed that PEDV could be divided into two genotypes (G1 and G2) and five subgenotypes (G1a, G1b, G2a, G2b, and G2c) based on complete sequence of S gene ( Fan et al, 2017 ; Hsueh et al, 2020 ; Wang H. et al, 2020 ; Wang X.W. et al, 2020 ).…”