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

Huinan Wang; Libo Zhang; Yuanbin Shang; Rongrong Tan; Mingxiang Ji; Xinliang Yue; Nannan Wang; Jun Liu; Chunhua Wang; Yonggang Li; Tiezhong Zhou

doi:10.1093/ve/veaa049

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

Virus Evol. 2020 Jul 10;6(2):veaa049. doi: 10.1093/ve/veaa049. eCollection 2020 Jul.

Authors

Affiliations

¹ Department of Basic Veterinary Medicine, College of Animal Husbandry & Veterinary Medicine, Jinzhou Medical University, Jinzhou 121000, China.
² Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
³ Beijing Institude of Feed Conrrol, Beijing 100107, China.
⁴ Department of Pathogenic Biology, School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou 121000, China.

Abstract

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.

Keywords: evolution; pathogenicity; porcine epidemic diarrhea virus; recombination; spike gene.