College of Life Sciences, Nanjing Agricultural University, Nanjing, 210095, China.
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing, 210014, China.
Nat Commun. 2022 Mar 18;13(1):1467. doi: 10.1038/s41467-022-29062-5.
Porcine deltacoronavirus (PDCoV) can experimentally infect a variety of animals. Human infection by PDCoV has also been reported. Consistently, PDCoV can use aminopeptidase N (APN) from different host species as receptors to enter cells. To understand this broad receptor usage and interspecies transmission of PDCoV, we determined the crystal structures of the receptor binding domain (RBD) of PDCoV spike protein bound to human APN (hAPN) and porcine APN (pAPN), respectively. The structures of the two complexes exhibit high similarity. PDCoV RBD binds to common regions on hAPN and pAPN, which are different from the sites engaged by two alphacoronaviruses: HCoV-229E and porcine respiratory coronavirus (PRCoV). Based on structure guided mutagenesis, we identified conserved residues on hAPN and pAPN that are essential for PDCoV binding and infection. We report the detailed mechanism for how a deltacoronavirus recognizes homologous receptors and provide insights into the cross-species transmission of PDCoV.
猪德尔塔冠状病毒（PDCoV）可在实验条件下感染多种动物，也有人类感染 PDCoV 的报道。PDCoV 可以利用不同宿主物种的氨肽酶 N（APN）作为受体进入细胞。为了了解 PDCoV 的广泛受体利用和种间传播，我们分别确定了 PDCoV 刺突蛋白受体结合域（RBD）与人和猪 APN（hAPN 和 pAPN）结合的晶体结构。这两个复合物的结构表现出高度的相似性。PDCoV RBD 结合到 hAPN 和 pAPN 的共同区域，这些区域与两种甲型冠状病毒（HCoV-229E 和猪呼吸冠状病毒（PRCoV））的结合位点不同。基于结构引导的诱变，我们鉴定了 hAPN 和 pAPN 上对 PDCoV 结合和感染至关重要的保守残基。我们报告了德尔塔冠状病毒识别同源受体的详细机制，并深入了解了 PDCoV 的跨种传播。
