一种类似中东呼吸综合征的蝙蝠冠状病毒在穿山甲中传播，并利用人类 DPP4 和宿主蛋白酶进入细胞。

A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry.

机构信息

CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China.

出版信息

Cell. 2023 Feb 16;186(4):850-863.e16. doi: 10.1016/j.cell.2023.01.019.

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——最常被走私的哺乳动物——是否在蝙蝠冠状病毒的人畜共患病传播中发挥作用。我们报告了一种新型 MERS 样冠状病毒在马来穿山甲中的传播，命名为 Manis javanica HKU4 相关冠状病毒（MjHKU4r-CoV）。在 86 只动物中，有 4 只通过 pan-CoV PCR 检测呈阳性，7 只血清学检测呈阳性（11%和 12.8%）。我们获得了 4 个几乎完全相同（99.9%）的基因组序列，其中一个病毒被分离（MjHKU4r-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，其增强作用依赖于一个弗林切割位点，而所有已知的蝙蝠 HKU4r-CoVs 中均不存在该位点。MjHKU4r-CoV-1 的刺突蛋白与人 DPP4 的结合亲和力更高，而 MjHKU4r-CoV-1 的宿主范围比蝙蝠 HKU4-CoV 更广。MjHKU4r-CoV-1 在人类气道和肠道器官以及 hDPP4 转基因小鼠中具有感染性和致病性。我们的研究强调了穿山甲作为冠状病毒潜在宿主在人类疾病出现中的重要性。