PDF(Pubmed)
Abstract：
Deltacoronavirus, widely distributed among pigs and wild birds, pose a significant risk of cross-species transmission, including potential human epidemics. Metagenomic analysis of bird samples from Qinghai Lake, China in 2021 reported the presence of Deltacoronavirus. A specific gene fragment of Deltacoronavirus was detected in fecal samples from wild birds at a positive rate of 5.94% (6/101). Next-generation sequencing (NGS) identified a novel Deltacoronavirus strain, which was closely related to isolates from the United Arab Emirates (2018), China (2022), and Poland (2023). Subsequently the strain was named A/black-headed gull/Qinghai/2021(BHG-QH-2021) upon confirmation of the Cytochrome b gene of black-headed gull in the sample. All available genome sequences of avian Deltacoronavirus, including the newly identified BHG-QH-2021 and 5 representative strains of porcine Deltacoronavirus (PDCoV), were classified according to ICTV criteria. In contrast to Coronavirus HKU15, which infects both mammals and birds and shows the possibility of cross-species transmission from bird to mammal host, our analysis revealed that BHG-QH-2021 is classified as Putative species 4. Putative species 4 has been reported to infect 5 species of birds but not mammals, suggesting that cross-species transmission of Putative species 4 is more prevalent among birds. Recombination analysis traced BHG-QH-2021 origin to dut148cor1 and MW01_1o strains, with MW01_1o contributing the S gene. Surprisingly, SwissModle prediction showed that the optimal template for receptor-binding domain (RBD) of BHG-QH-2021 is derived from the human coronavirus 229E, a member of the Alphacoronavirus, rather than the anticipated RBD structure of PDCoV of Deltacoronavirus. Further molecular docking analysis revealed that substituting the loop 1-2 segments of HCoV-229E significantly enhanced the binding capability of BHG-QH-2021 with human Aminopeptidase N (hAPN), surpassing its native receptor-binding domain (RBD). Most importantly, this finding was further confirmed by co-immunoprecipitation experiment that loop 1-2 segments of HCoV-229E enable BHG-QH-2021 RBD binding to hAPN, indicating that the loop 1-2 segment of the RBD in Putative species 4 is a probable key determinant for the virus ability to spill over into humans. Our results summarize the phylogenetic relationships among known Deltacoronavirus, reveal an independent putative avian Deltacoronavirus species with inter-continental and inter-species transmission potential, and underscore the importance of continuous surveillance of wildlife Deltacoronavirus.
摘要：
Deltacronvirus,广泛分布在猪和野鸟中，构成跨物种传播的重大风险，包括潜在的人类流行病。青海湖鸟类样品的宏基因组分析,中国在2021年报告了Deltacronavirus的存在。在野生鸟类的粪便样品中检测到Deltacrononavirus的特定基因片段，阳性率为5.94％（6/101）。下一代测序（NGS）鉴定出一种新型的Deltacronovirus株，与阿拉伯联合酋长国的分离株密切相关（2018年），中国(2022),波兰（2023年）。随后，在确认样品中黑头鸥的细胞色素b基因后，该菌株被命名为A/黑头鸥/青海/2021（BHG-QH-2021）。所有可用的鸟类Deltacronavirus基因组序列，包括新鉴定的BHG-QH-2021和5种代表性的猪Deltacoronavirus（PDCoV）菌株，根据ICTV标准进行分类。与冠状病毒HKU15相反，该病毒同时感染哺乳动物和鸟类，并显示出从鸟类到哺乳动物宿主的跨物种传播的可能性，我们的分析表明，BHG-QH-2021被归类为推定物种4。据报道，推定的物种4感染了5种鸟类，但没有感染哺乳动物，这表明推定物种4的跨物种传播在鸟类中更为普遍。重组分析将BHG-QH-2021的起源追溯到dut148cor1和MW01_1o菌株，MW01_1o贡献了S基因。令人惊讶的是,SwissModle预测表明，BHG-QH-2021受体结合域（RBD）的最佳模板来自人冠状病毒229E，Alphacoronavirus的成员，而不是Deltacronovirus的PDCoV的预期RBD结构。进一步的分子对接分析显示，取代HCoV-229E的环1-2片段显着增强了BHG-QH-2021与人氨肽酶N（hAPN）的结合能力，超越其天然受体结合域（RBD）。最重要的是,免疫共沉淀实验进一步证实了这一发现，即HCoV-229E的环1-2片段使BHG-QH-2021RBD能够与hAPN结合，表明推定物种4中RBD的环1-2片段可能是病毒溢出到人类中的能力的关键决定因素。我们的结果总结了已知的Deltacoronavirus之间的系统发育关系，揭示了一种具有大陆间和物种间传播潜力的独立推定的禽类Deltacoronavirus物种，并强调了持续监测野生动物Deltacoronavirus的重要性。
