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The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice

Author

Listed:
  • Linlin Bao

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Wei Deng

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Baoying Huang

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Hong Gao

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Jiangning Liu

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Lili Ren

    (Chinese Academy of Medical Sciences)

  • Qiang Wei

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Pin Yu

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Yanfeng Xu

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Feifei Qi

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Yajin Qu

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Fengdi Li

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Qi Lv

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Wenling Wang

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Jing Xue

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Shuran Gong

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Mingya Liu

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Guanpeng Wang

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Shunyi Wang

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Zhiqi Song

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Linna Zhao

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Peipei Liu

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Li Zhao

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Fei Ye

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Huijuan Wang

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Weimin Zhou

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Na Zhu

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Wei Zhen

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Haisheng Yu

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Xiaojuan Zhang

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

  • Li Guo

    (Chinese Academy of Medical Sciences)

  • Lan Chen

    (Chinese Academy of Medical Sciences)

  • Conghui Wang

    (Chinese Academy of Medical Sciences)

  • Ying Wang

    (Chinese Academy of Medical Sciences)

  • Xinming Wang

    (Chinese Academy of Medical Sciences)

  • Yan Xiao

    (Chinese Academy of Medical Sciences)

  • Qiangming Sun

    (Chinese Academy of Medical Sciences)

  • Hongqi Liu

    (Chinese Academy of Medical Sciences)

  • Fanli Zhu

    (Chinese Academy of Medical Sciences)

  • Chunxia Ma

    (Chinese Academy of Medical Sciences)

  • Lingmei Yan

    (Chinese Academy of Medical Sciences)

  • Mengli Yang

    (Chinese Academy of Medical Sciences)

  • Jun Han

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Wenbo Xu

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Wenjie Tan

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Xiaozhong Peng

    (Chinese Academy of Medical Sciences)

  • Qi Jin

    (Chinese Academy of Medical Sciences)

  • Guizhen Wu

    (National Institute for Viral Disease Control and Prevention, China CDC)

  • Chuan Qin

    (Chinese Academy of Medical Sciences
    Peking Union Medical College)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.

Suggested Citation

  • Linlin Bao & Wei Deng & Baoying Huang & Hong Gao & Jiangning Liu & Lili Ren & Qiang Wei & Pin Yu & Yanfeng Xu & Feifei Qi & Yajin Qu & Fengdi Li & Qi Lv & Wenling Wang & Jing Xue & Shuran Gong & Mingy, 2020. "The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice," Nature, Nature, vol. 583(7818), pages 830-833, July.
    • Handle: RePEc:nat:nature:v:583:y:2020:i:7818:d:10.1038_s41586-020-2312-y
    DOI: 10.1038/s41586-020-2312-y
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    Cited by:

    1. Shufeng Liu & Charles B. Stauft & Prabhuanand Selvaraj & Prabha Chandrasekaran & Felice D’Agnillo & Chao-Kai Chou & Wells W. Wu & Christopher Z. Lien & Clement A. Meseda & Cyntia L. Pedro & Matthew F., 2022. "Intranasal delivery of a rationally attenuated SARS-CoV-2 is immunogenic and protective in Syrian hamsters," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Tomokazu Yamaguchi & Midori Hoshizaki & Takafumi Minato & Satoru Nirasawa & Masamitsu N. Asaka & Mayumi Niiyama & Masaki Imai & Akihiko Uda & Jasper Fuk-Woo Chan & Saori Takahashi & Jianbo An & Akari , 2021. "ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Davida S. Smyth & Monica Trujillo & Devon A. Gregory & Kristen Cheung & Anna Gao & Maddie Graham & Yue Guan & Caitlyn Guldenpfennig & Irene Hoxie & Sherin Kannoly & Nanami Kubota & Terri D. Lyddon & M, 2022. "Tracking cryptic SARS-CoV-2 lineages detected in NYC wastewater," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    4. Srikanth Sadhu & Rajdeep Dalal & Jyotsna Dandotiya & Akshay Binayke & Virendra Singh & Manas Ranjan Tripathy & Vinayaka Das & Sandeep Goswami & Shakti Kumar & Zaigham Abbas Rizvi & Amit Awasthi, 2023. "IL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Xiaoming Hu & Shuang Wang & Shaotong Fu & Meng Qin & Chengliang Lyu & Zhaowen Ding & Yan Wang & Yishu Wang & Dongshu Wang & Li Zhu & Tao Jiang & Jing Sun & Hui Ding & Jie Wu & Lingqian Chang & Yimin C, 2023. "Intranasal mask for protecting the respiratory tract against viral aerosols," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. 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.
    7. Lucie Bernard-Raichon & Mericien Venzon & Jon Klein & Jordan E. Axelrad & Chenzhen Zhang & Alexis P. Sullivan & Grant A. Hussey & Arnau Casanovas-Massana & Maria G. Noval & Ana M. Valero-Jimenez & Jua, 2022. "Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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