Porcine epidemic diarrhea virus (PEDV) is a major pathogen in the global pig industry. Before 2010, the CV777 vaccine eradicated the classic strain. However, after 2010, a GII epidemic broke out in China (with a piglet mortality rate exceeding 90%). The failure of the classic vaccine revealed that the virus may escape immunity through antigenic drift or recombination, and the specific mechanism remains to be elucidated.
On July 2, 2025, a team from Northwest A&S University and the Lanzhou Veterinary Institute published a study in the journal BMC Vet Res based on 1,109 PEDV strains, revealing S gene mutations, recombination hotspots, and glycosylation variations, providing key support for vaccine development.
The results showed that GII strains (87.38%) drive PEDV evolution and prevalence through high-frequency mutations in the COE region (such as L521H), domain 0 recombination hotspots, and N62/N118 glycosylation variations, enhancing receptor binding and immune evasion.
Introduction
Analysis of the S gene of 1,109 PEDV strains in my country revealed that GII strains (dominant, with GIIa/b/c combined accounting for over 85%) evolve through a dual strategy of "sialic acid binding and immune evasion." Their recombination hotspots (D0 domain) and unique glycosylation patterns (N62/N118 sites) drive cross-species transmission, providing key insights for vaccine optimization and regional prevention and control.
Research Results
1. GII strains dominate
A phylogenetic tree shows that PEDV strains in China belong to two major clades: GI (classical) and GII (variant), encompassing six subtypes. After 2010, GII became the dominant prevalent strain. The proportion of GIIa has been declining since 2014, while GIIc has steadily increased. GIIb remains stable, with the latter two subtypes currently constituting the predominant prevalent strains.
Figure 1. Phylogenetic analysis of S gene sequences from 1099 PEDV isolates in this study.
Gla (yellow), Glb (brown), S-INDEL (purple),
GIIa (red), GIIb (blue), and GIIc (green).
Figure 2. Relative frequency of different virus subtypes by year.
Figure 3. Geographic Distribution of PEDV in Different Regions of China
Provinces are divided into seven regions based on distance: North China, Northeast China, East China, Central China, South China, Southwest China, and Northwest China.
Conclusion: Geographic distribution analysis shows that Guangdong, Sichuan, and Henan provinces have the highest PEDV prevalence.
2. S Protein Amino Acid Mutations
Comparison of neutralizing epitopes in the S protein of various strains revealed eight common mutations with high frequency in the COE region, including L521H and S523G, as well as the cross-subtype A517S variant. The SS6 region is dominated by the Y766S mutation. The GIIa strain has a key insertion at positions 608-609. The SS2 and 2C10 epitopes are highly conserved, suggesting that the virus escapes immune pressure through targeted epitope mutations.
Figure 4. Amino Acid Mutation Analysis of Neutralizing Epitopes SS2 (A),
SS6 (B), 2C10 (C), and COE (D) in the Chinese PEDV S protein
Conclusion: GII strains exhibit frequent mutations in the COE and SS6 regions (e.g., L521H/S523G, Y766S), but the SS2 and 2C10 epitopes are highly conserved, enabling them to escape neutralizing antibodies.
3. Recombination Analysis
Research has shown that recombination is a key driving force in PEDV viral evolution. Analysis indicates that GII strains are the primary parental source of recent recombination events in the S gene of PEDV strains.
Specifically: GIb recombinant strains are mostly formed by recombination between GI and GII strains, and their recombination regions all include Domain 0; GIIb recombinant strains are mainly produced by recombination between different GIIb strains, and the recombination regions mostly cover HR2, TM and Domain 0; part of the GIIc recombinant strains originate from recombination between GIIb strains, and the region basically includes FP and HR1 of S1 and S2, while the other part is the recombinant of GIa and GIIb strains, and the recombination region also includes Domain 0.
Table 1. Information on S gene recombination events in 282 PEDV strains in China from 2020 to 2024
Conclusion: In recent years, S gene recombination events have primarily occurred in GII strains, and all recombination types involve key regions such as Domain 0.
4. N-Glycosylation Site Variation
Studies have found that N-glycosylation is crucial for PEDV invasion and immune evasion. G1 strains (containing G1a/G1b/S-INDELs) have similar glycosylation patterns to CV777 strains and lack newly added sites. However, GII strains (GIIa/GIIb/GIIc) exhibit newly added, highly specific sites (i.e., N62 and N118) in Domain 0, potentially impacting viral-host interactions and immune recognition.
Figure 6. Compared with the CV777 vaccine strain, the S protein of different PEDV subtypes exhibits differences in the number of key N-glycosylation sites.
Conclusion: Compared with the CV777 strain, all subtypes generally lost glycosylation at sites 127, 511, and 553. Meanwhile, subtype GII acquired new glycosylation patterns at sites 62 and 118.
Summary
This study revealed three key evolutionary characteristics of PEDV viruses in China: GII subtypes achieve the dual advantages of "high sialic acid affinity and immune escape" through mutations in the D0 domain; recombination hotspots concentrated in the D0 region drive adaptive evolution; and glycosylation modifications at sites N62/N118 mediate immune escape.
Thus, targeted prevention and control strategies are proposed: developing a multivalent mRNA vaccine targeting aglycosylated epitopes, establishing a surveillance system based on recombination hotspots, and assessing the risk of cross-species transmission.
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