• The glycosylation variant at r...

Treffer: The glycosylation variant at residue 381 of the spike protein contributes to virulence shifts in porcine epidemic diarrhea virus during both natural field transmission and laboratory cell passaging with poor cross-protection.

Title:
The glycosylation variant at residue 381 of the spike protein contributes to virulence shifts in porcine epidemic diarrhea virus during both natural field transmission and laboratory cell passaging with poor cross-protection.
Authors:
Li Z; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Ma Z; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Li Y; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Zhao X; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Zheng Y; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Li Y; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Feng Y; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Guo X; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Zheng Z; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Xu L; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Zhang J; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Zheng H; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China., Xiao S; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
Source:
Journal of virology [J Virol] 2025 Dec 23; Vol. 99 (12), pp. e0156125. Date of Electronic Publication: 2025 Nov 24.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE
Imprint Name(s):
Publication: Washington Dc : American Society For Microbiology
Original Publication: Baltimore, American Society for Microbiology.
MeSH Terms:
Porcine epidemic diarrhea virus*/pathogenicity , Porcine epidemic diarrhea virus*/genetics , Porcine epidemic diarrhea virus*/immunology , Spike Glycoprotein, Coronavirus*/genetics , Spike Glycoprotein, Coronavirus*/immunology , Spike Glycoprotein, Coronavirus*/metabolism , Spike Glycoprotein, Coronavirus*/chemistry , Swine Diseases*/virology , Swine Diseases*/immunology , Swine Diseases*/transmission , Coronavirus Infections*/veterinary , Coronavirus Infections*/virology , Coronavirus Infections*/immunology , Coronavirus Infections*/transmission , Cross Protection*, Animals ; Swine ; Glycosylation ; Virulence/genetics ; Virus Shedding ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antibodies, Viral/blood ; Mutation ; Serial Passage ; Diarrhea/virology
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Grant Information:
32402888 National Natural Science Foundation of China; 23JRRA1476 Joint Research Foundation of Gansu Province; 24JRRA804 Joint Research Foundation of Gansu Province; 22ZD6NA001 Major Scientific and Technological Special Project of Gansu Province; CARS-35 Agriculture Research System of China; 2024M753579 China Postdoctoral Science Foundation
Contributed Indexing:
Keywords: cross-protection; glycosylation mutation; porcine epidemic diarrhea virus; spike protein; viral pathogenesis
Substance Nomenclature:
0 (Spike Glycoprotein, Coronavirus)
0 (Antibodies, Neutralizing)
0 (Antibodies, Viral)
Entry Date(s):
Date Created: 20251124 Date Completed: 20251223 Latest Revision: 20251225
Update Code:
20251225
PubMed Central ID:
PMC12724335
DOI:
10.1128/jvi.01561-25
PMID:
41277840
Database:
MEDLINE

Weitere Informationen

The virulence and immunogenicity of porcine epidemic diarrhea virus (PEDV) vary during field circulation and cell culture passage (such as when the GI CV777 strain is attenuated through serial passaging). This study revealed that the glycosylation site mutation at position 381 (N381K) of the S protein is associated with these phenomena. Compared with piglets inoculated with P13 virus, piglets inoculated with P100 (N381K) of virulent GX223 exhibited delayed diarrhea, viral shedding, and mortality. Using the virulent rCH/SX/2016-S <subscript>HNXP</subscript> strain (rPEDV-S <subscript>wt</subscript> ) as the backbone, we generated rPEDV-S <subscript>N381K</subscript> . While both the wild-type and mutant strains showed similar growth in vitro and in 2-day-old piglets, rPEDV-S <subscript>N381K</subscript> caused milder diarrhea and lower mortality. In 5-day-old piglets, the mutant strain also induced delayed viral shedding and milder diarrhea. At 21 days after post-infection, all the piglets were challenged with the parental strain. The pigs in both the rPEDV-S <subscript>N381K</subscript> and rPEDV-S <subscript>wt</subscript> groups produced high IgA/IgG levels, but the rPEDV-S <subscript>N381K</subscript> -inoculated piglets presented higher fecal viral loads and lower neutralizing antibody titers against the parental strain. Molecular modeling suggests that N381K alters antigenic epitope interactions, which may affect virulence and immunogenicity. While this study has the limitation of a relatively small sample size in the animal studies, the results collectively demonstrate that S protein glycosylation mutations influence PEDV virulence and contribute to reduced cross-protective vaccine efficacy, offering important insights for PEDV pathogenesis research and vaccine development.
Importance: Porcine epidemic diarrhea virus (PEDV) continues to cause substantial economic losses in the global swine industry, with emerging strains challenging existing vaccine strategies. This study identifies the N381K glycosylation site mutation in the S protein of PEDV as a factor involved in variations in virulence during natural transmission and laboratory adaptation. Crucially, the mutant induces suboptimal neutralizing immunity against the prevalent strain, revealing a mechanism by which classical-strain vaccines may provide limited protection against currently circulating strains. Our findings reveal how a single glycan modification modulates both pathogenicity and immunogenicity, providing critical insights for the development of effective vaccines against circulating PEDV variants.

The authors declare no conflict of interest.