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

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 pos...

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Detalles Bibliográficos
Autores principales: Chen, Jing, Yang, Xinglou, Si, Haorui, Gong, Qianchun, Que, Tengcheng, Li, Jing, Li, Yang, Wu, Chunguang, Zhang, Wei, Chen, Ying, Luo, Yun, Zhu, Yan, Li, Bei, Luo, Dongsheng, Hu, Ben, Lin, Haofeng, Jiang, Rendi, Jiang, Tingting, Li, Qian, Liu, Meiqin, Xie, Shizhe, Su, Jia, Zheng, Xiaoshuang, Li, Ang, Yao, Yulin, Yang, Yong, Chen, Panyu, Wu, Aiqiong, He, Meihong, Lin, Xinhua, Tong, Yigang, Hu, Yanling, Shi, Zheng-Li, Zhou, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933427/
https://www.ncbi.nlm.nih.gov/pubmed/36803605
http://dx.doi.org/10.1016/j.cell.2023.01.019
Descripción
Sumario: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.