Mao Li, Cai Xuhang, Li Jizong, Li Xia, Li Siyuan, Li Wenliang, Lu Honghui, Dong Yichun, Zhai Junjun, Xu Xingang, Li Bin
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, China.
Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture and Rural Affairs, Nanjing, China.
PLoS Pathog. 2025 Mar 18;21(3):e1012974. doi: 10.1371/journal.ppat.1012974. eCollection 2025 Mar.
Betacoronavirus is a causative agent of respiratory and enteric diseases in humans and animals. Several ruminants are recognized to be intermediate hosts in the transmission of emerging coronaviruses from reservoir hosts to humans. Here, we first report a novel Betacoronavirus isolated from goats suffering from diarrhea in China, putatively named caprine coronavirus (cpCoV). Full-genome characterization and nuclear acid comparisons demonstrated that this virus is an evolutionarily distinct Betacoronavirus belonging to the subgenus Embecovirus and is a Betacoronavirus 1 species. Notably, on phylogenetic trees based on complete genomes and RdRp, S, and N genes, the cpCoVs were grouped into a clade distinct from other Betacoronavirus strains and were closely related to the HKU23- and HKU23-associated coronaviruses. CpCoV possessed a unique genome organization with a truncated NS4a protein and an elongated NS4b protein that showed no significant matches in the GenBank database. The homology of the S and NS4a-4b genes between cpCoV and Embecovirus was less than 95%. Analysis revealed possible recombination events occurred during the evolution of cpCoV and HKU23, and there are striking similarities between the two viruses in evolutionary terms. In addition, cpCoV showed a narrow cell tropism, replicating in human- and bovine-origin cells in vitro, and caused diarrhea and enteric pathologic changes in goats and calves in vivo. We have provided epidemiological, virological, evolutionary, and experimental evidence that cpCoV is a novel etiological agent for enteric disease in goats. Evidently, a spilling-over event might have occurred between ruminants, including goats, camels, cattle, and wild animals. This study highlights the importance of identifying coronavirus diversity and inter-species transmission in ruminants worldwide, broadens our understanding of the ecology of coronaviruses, and aids in the prevention of animal-to-human transmission and outbreaks.
β冠状病毒是人和动物呼吸道及肠道疾病的病原体。几种反刍动物被认为是新兴冠状病毒从储存宿主传播给人类的中间宿主。在此，我们首次报道了从中国患腹泻山羊中分离出的一种新型β冠状病毒，暂定名为山羊冠状病毒（cpCoV）。全基因组特征分析和核酸比较表明，该病毒是一种在进化上独特的β冠状病毒，属于Embecovirus亚属，是β冠状病毒1物种。值得注意的是，在基于完整基因组以及RdRp、S和N基因构建的系统发育树上，cpCoV被归为一个与其他β冠状病毒株不同的进化枝，且与HKU23及与HKU23相关的冠状病毒密切相关。CpCoV具有独特的基因组结构，其NS4a蛋白截短，NS4b蛋白延长，在GenBank数据库中未显示出明显匹配。cpCoV与Embecovirus的S基因和NS4a - 4b基因的同源性低于95%。分析显示cpCoV和HKU23在进化过程中可能发生了重组事件，并且在进化方面这两种病毒存在显著相似性。此外，cpCoV表现出狭窄的细胞嗜性，在体外可在人源和牛源细胞中复制，在体内可导致山羊和犊牛腹泻及肠道病理变化。我们提供了流行病学、病毒学、进化和实验证据，证明cpCoV是山羊肠道疾病的一种新型病原体。显然，包括山羊、骆驼、牛和野生动物在内的反刍动物之间可能发生了溢出事件。这项研究强调了识别全球反刍动物中冠状病毒多样性和种间传播的重要性，拓宽了我们对冠状病毒生态学的理解，并有助于预防动物向人类的传播和疫情爆发。
