Abstract Outbreaks of a new variant of porcine epidemic diarrhea virus (PEDV) at the end of 2010 have raised interest in the mutation and recombination of PEDV. A PEDV strain (CN/Liaoning25/2018) isolated from a clinical outbreak of piglet diarrhea contained a 49-bp deletion in the ORF3 gene. This deletion is considered a genetic characteristic of low pathogenic attenuated vaccine strains. However, CN/Liaoning25/2018 was highly pathogenic. Complete genome sequencing, identity analysis, phylogenetic tree construction, and recombination analysis showed that this virus was a recombinant strain containing the Spike (S) gene from the highly pathogenic CN/GDZQ/2014 strain and the remaining genomic regions from the low pathogenic vaccine isolate SQ2014. Histopathology and immunohistochemistry results confirmed that this strain was highly pathogenic and indicated that intestinal epithelial cell vacuolation was positively correlated with the intensity and density of PEDV antigens. A new natural recombination model for PEDV was identified. Our results suggest that new highly pathogenic recombinant strains in the field may be generated by recombination between low pathogenic attenuated live PEDV vaccines and pathogenic circulating PEDV strains. Our findings also highlight that the 49-bp deletion of the ORF3 gene in low pathogenic attenuated vaccine strains will no longer be a reliable standard to differentiate the classical vaccine attenuated from the field strains.

中文翻译：

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高致病性猪流行性腹泻病毒通过低致病性疫苗分离物和刺突基因中的高致病性菌株的自然重组的出现和进化

摘要 2010年底猪流行性腹泻病毒（PEDV）新变种的爆发引起了人们对PEDV突变和重组的兴趣。从一次临床爆发的仔猪腹泻中分离出的 PEDV 毒株（CN/Liaoning25/2018）在 ORF3 基因中含有 49 bp 的缺失。这种缺失被认为是低致病性减毒疫苗株的遗传特征。然而，CN/Liaoning25/2018 具有高致病性。完整的基因组测序、身份分析、系统发育树构建和重组分析表明，该病毒为重组毒株，含有来自高致病性 CN/GDZQ/2014 毒株的 Spike (S) 基因和来自低致病性疫苗分离株的其余基因组区域SQ2014。组织病理学和免疫组化结果证实该菌株具有高致病性，表明肠上皮细胞空泡化与PEDV抗原的强度和密度呈正相关。确定了一种新的 PEDV 自然重组模型。我们的结果表明，该领域新的高致病性重组毒株可能是通过低致病性减毒活 PEDV 疫苗和致病性循环 PEDV 毒株之间的重组产生的。我们的研究结果还强调，低致病性减毒疫苗株中 ORF3 基因的 49 bp 缺失将不再是区分经典减毒疫苗与野毒株的可靠标准。确定了一种新的 PEDV 自然重组模型。我们的结果表明，该领域新的高致病性重组毒株可能是通过低致病性减毒活 PEDV 疫苗和致病性循环 PEDV 毒株之间的重组产生的。我们的研究结果还强调，低致病性减毒疫苗株中 ORF3 基因的 49 bp 缺失将不再是区分经典减毒疫苗与野毒株的可靠标准。确定了一种新的 PEDV 自然重组模型。我们的结果表明，该领域新的高致病性重组毒株可能是通过低致病性减毒活 PEDV 疫苗和致病性循环 PEDV 毒株之间的重组产生的。我们的研究结果还强调，低致病性减毒疫苗株中 ORF3 基因的 49 bp 缺失将不再是区分经典减毒疫苗与野毒株的可靠标准。