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

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

  • Cell. 2023 Feb 16;186(4):850-863.e16. doi: 10.1016/j.cell.2023.01.019.
Jing Chen 1,  Xinglou Yang 1,  Haorui Si 2,  Qianchun Gong 3,  Tengcheng Que 4,  Jing Li 5,  Yang Li 1,  Chunguang Wu 2,  Wei Zhang 1,  Ying Chen 2,  Yun Luo 2,  Yan Zhu 1,  Bei Li 1,  Dongsheng Luo 1,  Ben Hu 1,  Haofeng Lin 2,  Rendi Jiang 6,  Tingting Jiang 1,  Qian Li 2,  Meiqin Liu 2,  Shizhe Xie 2,  Jia Su 2,  Xiaoshuang Zheng 2,  Ang Li 2,  Yulin Yao 1,  Yong Yang 2,  Panyu Chen 7,  Aiqiong Wu 7,  Meihong He 7,  Xinhua Lin 8,  Yigang Tong 9,  Yanling Hu 10,  Zheng-Li Shi 11,  Peng Zhou 12
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
  • 2 CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China.
  • 3 State Key Laboratory of Genetic Engineering, School of Life Sciences, Greater Bay Area Institute of Precision Medicine (Guangzhou), Zhongshan Hospital, Fudan University Shanghai, Shanghai 200438, China; Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University and School of Life Sciences of Fudan University, Chengdu 610041, China.
  • 4 Guangxi Zhuang Autonomous Region Terrestrial Wildlife Medical-aid and Monitoring Epidemic Diseases Research Center, Nanning 530028, Guangxi, China; Faculty of Data Science, City University of Macau, Beijing, China.
  • 5 Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
  • 6 State Key Laboratory of Genetic Engineering, School of Life Sciences, Greater Bay Area Institute of Precision Medicine (Guangzhou), Zhongshan Hospital, Fudan University Shanghai, Shanghai 200438, China.
  • 7 Guangxi Zhuang Autonomous Region Terrestrial Wildlife Medical-aid and Monitoring Epidemic Diseases Research Center, Nanning 530028, Guangxi, China.
  • 8 State Key Laboratory of Genetic Engineering, School of Life Sciences, Greater Bay Area Institute of Precision Medicine (Guangzhou), Zhongshan Hospital, Fudan University Shanghai, Shanghai 200438, China; Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University and School of Life Sciences of Fudan University, Chengdu 610041, China. Electronic address: xlin@fudan.edu.cn.
  • 9 Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. Electronic address: tongyigang@mail.buct.edu.cn.
  • 10 Institute of Life Sciences, Guangxi Medical University, Nanning 530021, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, Guangxi, China. Electronic address: huyanling@gxmu.edu.cn.
  • 11 CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. Electronic address: zlshi@wh.iov.cn.
  • 12 CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; Guangzhou Laboratory, No. 9 Xing Dao Huan Bei Road, Guangzhou International Bio Island, Guangzhou 51005, Guangdong Province, China. Electronic address: peng.zhou@wh.iov.cn.
PMID: 36803605 DOI: 10.1016/j.cell.2023.01.019
Abstract

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.

Keywords

bat MERS-like coronavirus; dipeptidyl peptidase-4; furin cleavage site; pangolin.

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