Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility
Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility
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DOI：
10.1073/pnas.1802879115
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发表时间：
2018-05-29
影响因子：
11.1
通讯作者：
Bosch, Berend-Jan
中科院分区：
文献类型：
--
作者：
Li, Wentao;Hulswit, Ruben J. G.;Bosch, Berend-Jan
猪三角洲冠状病毒（PDCoV）是2012年发现的一种常见的猪肠道病原体，分布于世界各地。然而，这种病毒的来源和进化历史尚不清楚。PDCoV属于三角洲冠状病毒属，主要包括禽类CoV。系统发育分析表明，PDCoV起源于鸟类和哺乳动物之间的宿主转换事件。对PDCoV受体参与的深入了解可能会揭示这种特殊现象。在这里，我们报告PDCoV采用宿主氨肽酶N（APN）作为进入受体，并通过其刺突（S）蛋白的结构域B与APN相互作用。APN敲除可显著降低PDCoV对猪细胞的感染，并在APN表达重建后得以挽救。此外，我们观察到PDCoV有效地感染了不寻常的广泛物种范围的细胞，包括人类和鸡。因此，发现PDCoV S靶向APN的遗传上保守的催化结构域。此外，猪、猫、人和鸡APN的瞬时表达使细胞易受PDCoV感染。PDCoV与APN上种间保守位点的结合可能有助于PDCoV直接传播给非宿主物种，包括人类，这可能反映了PDCoV祖先病毒能够突破鸟类和哺乳动物之间物种屏障的机制。APN细胞表面蛋白也被α冠状病毒属的几个成员使用。因此，我们的数据构成了使用相同受体的不同属的CoV的第二次鉴定，这意味着CoV受体选择受到仍然知之甚少的特定限制。
Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the Deltacoronavirus genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the Alphacorona-virus genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood.