Investigation of the role of the spike protein in reversing the virulence of the highly virulent Taiwan porcine epidemic diarrhea virus Pintung 52 strains and its attenuated counterpart
Journal
Viruses
Journal Volume
12
Journal Issue
1
Date Issued
2019
Author(s)
Kao, C.-F.
Abstract
Porcine epidemic diarrhea virus (PEDV) has continuously caused severe economic losses to the global swine industries; however, no successful vaccine against PEDV has been developed. In this study, we generated four autologous recombinant viruses, including the highly virulent iPEDVPT-P5, attenuated iPEDVPT-P96, and two chimeric viruses (iPEDVPT-P5-96S and iPEDVPT-P96-5S) with the reciprocally exchanged spike (S) gene, to study the role of the S gene in PEDV pathogenesis. A deeper understanding of PEDV attenuation will aid in the rational design of a live attenuated vaccine (LAV) using reverse genetics system. Our results showed that replacing the S gene from the highly virulent iPEDVPT-P5 led to complete restoration of virulence of the attenuated iPEDVPT-P96, with nearly identical viral shedding, diarrhea pattern, and mortality rate as the parental iPEDVPT-P5. In contrast, substitution of the S gene with that from the attenuated iPEDVPT-P96 resulted in partial attenuation of iPEDVPT-P5, exhibiting similar viral shedding and diarrhea patterns as the parental iPEDVPT-P96 with slightly severe histological lesions and higher mortality rate. Collectively, our data confirmed that the attenuation of the PEDVPT-P96 virus is primarily attributed to mutations in the S gene. However, mutation in S gene alone could not fully attenuate the virulence of iPEDVPT-P5. Gene (s) other than S gene might also play a role in determining virulence. ? 2019 by the authors
Subjects
Attenuation; PEDV; Reverse genetics; Spike protein; Virulent determinant
SDGs
Other Subjects
virus spike protein; coronavirus spike glycoprotein; live vaccine; virus vaccine; amino acid sequence; amino acid substitution; animal cell; animal experiment; animal model; animal tissue; Article; controlled study; diarrhea; gene mutation; gene sequence; histopathology; immunofluorescence; immunohistochemistry; mortality rate; nonhuman; nucleotide sequence; piglet; Porcine epidemic diarrhea virus; Porcine epidemic diarrhea virus pintung 5; Porcine epidemic diarrhea virus pintung 52; Porcine epidemic diarrhea virus pintung 96; real time polymerase chain reaction; S gene; sequence analysis; syncytium; viral plaque assay; virus gene; virus morphology; virus shedding; virus titration; virus virulence; animal; Chlorocebus aethiops; Coronavirus infection; feces; genetics; mutation; pathogenicity; pig; Porcine epidemic diarrhea virus; reverse genetics; swine disease; Taiwan; Vero cell line; virology; virulence; Animals; Chlorocebus aethiops; Coronavirus Infections; Diarrhea; Feces; Mutation; Porcine epidemic diarrhea virus; Reverse Genetics; Spike Glycoprotein, Coronavirus; Swine; Swine Diseases; Taiwan; Vaccines, Attenuated; Vero Cells; Viral Vaccines; Virulence; Virus Shedding
Type
journal article