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

文献类型： 外文期刊

第一作者： Ma, Zhiqian

作者： Ma, Zhiqian;Li, Zhiwei;Li, Yongqi;Zhao, Xiaojing;Zheng, Congsen;Li, Yang;Guo, Xuyang;Xu, Lele;Zheng, Zifang;Liu, Guangliang;Zheng, Haixue;Xiao, Shuqi;Ma, Zhiqian;Li, Zhiwei;Li, Yongqi;Zhao, Xiaojing;Zheng, Congsen;Li, Yang;Guo, Xuyang;Xu, Lele;Zheng, Zifang;Liu, Guangliang;Zheng, Haixue;Xiao, Shuqi

作者机构：

关键词： porcine epidemic diarrhea virus; virulence evolution; spike protein; N-linked glycosylation; reverse genetic system

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：3.8； 五年影响因子：3.9 ）

ISSN： 0022-538X

年卷期： 2025 年 99 卷 4 期

页码：

收录情况： SCI

摘要： 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-Swt as the backbone, among which rPEDV-Smut62,rPEDVSmut118,rPEDVSmut131, and rPEDV-Smut722 were successfully rescued, but rPEDV-Smut235 was not. Compared to infection with rPEDV-Swt (100%), infection with rPEDV-Smut62 and rPEDV-Smut722 resulted in lower mortality in piglets (33%), and although rPEDV-Smut118 and rPEDV-Smut131 resulted in high mortality (100%), death was delayed. All surviving piglets were challenged orally with rPEDV-Swt at 21 days post-infection. The piglets in the rPEDV-Smut62 and rPEDV-Smut722 groups produced high levels of IgG, IgA, and cross-protective neutralizing antibodies, which protected the piglets after rPEDV-Swt challenge. Furthermore, the change in the structures of the rPEDV-Smut62 and rPEDVSmut722 S proteins predicted with high precision by AlphaFold 3 may be the cause of the attenuated virulence. Our data provide a unique perspective on the molecular mechanism of PEDV virulence evolution from the GI to the GII subtype and identify the targets of PED live attenuated vaccines.

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