It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.

目前尚不清楚穿山甲这种被贩运最多的哺乳动物是否在蝙蝠冠状病毒的人畜共患传播中发挥了作用。我们报告了一种名为Manis javanica的马来亚穿山甲中新型 MERS 样冠状病毒的传播HKU4 相关冠状病毒 (MjHKU4r-CoV)。在 86 只动物中，4 只通过 pan-CoV PCR 检测呈阳性，7 只检测血清阳性（分别为 11% 和 12.8%）。获得了四个几乎相同（99.9%）的基因组序列，并分离出一种病毒（Mj​​HKU4r-CoV-1）。该病毒利用人二肽基肽酶 4 (hDPP4) 作为受体和宿主蛋白酶进行细胞感染，并通过所有已知蝙蝠 HKU4r-CoV 中都不存在的弗林蛋白酶切割位点增强了这种切割位点。MjHKU4r-CoV-1 刺突显示出对 hDPP4 具有更高的结合亲和力，并且 MjHKU4r-CoV-1 的宿主范围比蝙蝠 HKU4-CoV 更广。MjHKU4r-CoV-1 在人类呼吸道和肠道器官以及 hDPP4 转基因小鼠中具有传染性和致病性。我们的研究强调了穿山甲作为冠状病毒宿主的重要性，这些冠状病毒可能会引发人类疾病。