Isolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice

Luo-Yuan Xia, Zhen-Fei Wang, Xiao-Ming Cui, Yuan-Guo Li, Run-Ze Ye, Dai-Yun Zhu, Fang-Xu Li, Jie Zhang, Wen-Hao Wang, Ming-Zhu Zhang, Wan-Ying Gao, Lian-Feng Li, Teng-Cheng Que, Tie-Cheng Wang, Na Jia, Jia-Fu Jiang (), Yu-Wei Gao () and Wu-Chun Cao ()
Additional contact information
Luo-Yuan Xia: Cheeloo College of Medicine, Shandong University
Zhen-Fei Wang: Cheeloo College of Medicine, Shandong University
Xiao-Ming Cui: Beijing Institute of Microbiology and Epidemiology
Yuan-Guo Li: Changchun Veterinary Research Institute, Changchun
Run-Ze Ye: Cheeloo College of Medicine, Shandong University
Dai-Yun Zhu: Beijing Institute of Microbiology and Epidemiology
Fang-Xu Li: Changchun Veterinary Research Institute, Changchun
Jie Zhang: Beijing Institute of Microbiology and Epidemiology
Wen-Hao Wang: Changchun Veterinary Research Institute, Changchun
Ming-Zhu Zhang: Cheeloo College of Medicine, Shandong University
Wan-Ying Gao: Cheeloo College of Medicine, Shandong University
Lian-Feng Li: Cheeloo College of Medicine, Shandong University
Teng-Cheng Que: Terrestrial Wildlife Rescue and Epidemic Diseases Surveillance Center of Guangxi
Tie-Cheng Wang: Changchun Veterinary Research Institute, Changchun
Na Jia: Beijing Institute of Microbiology and Epidemiology
Jia-Fu Jiang: Beijing Institute of Microbiology and Epidemiology
Yu-Wei Gao: Changchun Veterinary Research Institute, Changchun
Wu-Chun Cao: Cheeloo College of Medicine, Shandong University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin1. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4.

Date: 2024
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DOI: 10.1038/s41467-024-45453-2

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