Changes in the motifs in the D0 and SD2 domains of the S protein drive the evolution of virulence in enteric coronavirus porcine epidemic diarrhea virus

作者：Zhiqian Ma, Zhiwei Li, Yongqi Li, Xiaojing Zhao, Congsen Zheng, Yang Li, Xuyang Guo, Lele Xu, Zifang Zheng, Guangliang Liu, Haixue Zheng, Shuqi Xiao · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.02092-24 · 被引用次数：13 · 研究领域：Animal Virus Infections Studies、Virus-based gene therapy research、Viral gastroenteritis research and epidemiology

ABSTRACT Since 2010, highly virulent mutant GII subtype porcine epidemic diarrhea virus (PEDV) strains derived from GI subtype strains have caused significant economic losses in the pig industry. However, the molecular mechanism of PEDV virulence evolution remains unclear. It has been predicted that, compared to the S proteins of GI strains, five N-linked glycosylation sites have changed in the highly virulent GII PEDV strains. To investigate how changes in these sites affect PEDV virulence, we constructed five recombinant strains harboring the above mutation sites using the GII subtype rPEDV-S wt as the backbone, among which rPEDV-S mut62 , rPEDV-S mut118 , rPEDV-S mut131 , and rPEDV-S mut722 were successfully rescued, but rPEDV-S mut235 was not. Compared to infection with rPEDV-S wt (100%), infection with rPEDV-S mut62 and rPEDV-S mut722 resulted in lower mortality in piglets (33%), and although rPEDV-S mut118 and rPEDV-S mut131 resulted in high mortality (100%), death was delayed. All surviving piglets were challenged orally with rPEDV-S wt at 21 days post-infection. The piglets in the rPEDV-S mut62 and rPEDV-S mut722 groups produced high levels of IgG, IgA, and cross-protective neutralizing antibodies, which protected the piglets after rPEDV-S wt challenge. Furthermore, the change in the structures of the rPEDV-S mut62 and rPEDV-S mut722 S proteins predicted with high precision by AlphaFold 3 may be the cause of the attenuated virulence. Our data provide a unique perspect...