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

作者：Zhiwei Li, Zhiqian Ma, Yongqi Li, Xiaojing Zhao, Yong‐Hui Zheng, Yang Li, Yingtong Feng, Xuyang Guo, Zifang Zheng, Lele Xu, Jianwu Zhang, Haixue Zheng, Shuqi Xiao · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.01561-25 · 被引用次数：3 · 研究领域：Animal Virus Infections Studies、Animal Disease Management and Epidemiology、Virus-based gene therapy research

ABSTRACT 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 HNXP strain (rPEDV-S wt ) as the backbone, we generated rPEDV-S N381K . While both the wild-type and mutant strains showed similar growth in vitro and in 2-day-old piglets, rPEDV-S N381K 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 N381K and rPEDV-S wt groups produced high IgA/IgG levels, but the rPEDV-S N381K -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 P...