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

Author

Listed:
  • Luo-Yuan Xia

    (Cheeloo College of Medicine, Shandong University)

  • Zhen-Fei Wang

    (Cheeloo College of Medicine, Shandong University
    Changchun Veterinary Research Institute, Changchun)

  • Xiao-Ming Cui

    (Beijing Institute of Microbiology and Epidemiology
    Chinese Academy of Medical Sciences)

  • 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
    Chinese Academy of Medical Sciences)

  • Jia-Fu Jiang

    (Beijing Institute of Microbiology and Epidemiology
    Chinese Academy of Medical Sciences)

  • Yu-Wei Gao

    (Changchun Veterinary Research Institute, Changchun)

  • Wu-Chun Cao

    (Cheeloo College of Medicine, Shandong University
    Beijing Institute of Microbiology and Epidemiology
    Chinese Academy of Medical Sciences)

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.

Suggested Citation

  • 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, 2024. "Isolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45453-2
    DOI: 10.1038/s41467-024-45453-2
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