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Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice

Author

Listed:
  • Fatai S. Oladunni

    (Texas Biomedical Research Institute)

  • Jun-Gyu Park

    (Texas Biomedical Research Institute)

  • Paula A. Pino

    (Texas Biomedical Research Institute)

  • Olga Gonzalez

    (Texas Biomedical Research Institute)

  • Anwari Akhter

    (Texas Biomedical Research Institute)

  • Anna Allué-Guardia

    (Texas Biomedical Research Institute)

  • Angélica Olmo-Fontánez

    (Texas Biomedical Research Institute
    University of Texas Health Science Center at San Antonio)

  • Shalini Gautam

    (Texas Biomedical Research Institute)

  • Andreu Garcia-Vilanova

    (Texas Biomedical Research Institute)

  • Chengjin Ye

    (Texas Biomedical Research Institute)

  • Kevin Chiem

    (Texas Biomedical Research Institute
    University of Texas Health Science Center at San Antonio)

  • Colwyn Headley

    (Texas Biomedical Research Institute)

  • Varun Dwivedi

    (Texas Biomedical Research Institute)

  • Laura M. Parodi

    (Texas Biomedical Research Institute)

  • Kendra J. Alfson

    (Texas Biomedical Research Institute)

  • Hilary M. Staples

    (Texas Biomedical Research Institute)

  • Alyssa Schami

    (Texas Biomedical Research Institute
    University of Texas Health Science Center at San Antonio)

  • Juan I. Garcia

    (Texas Biomedical Research Institute)

  • Alison Whigham

    (Texas Biomedical Research Institute)

  • Roy Neal Platt

    (Texas Biomedical Research Institute)

  • Michal Gazi

    (Texas Biomedical Research Institute)

  • Jesse Martinez

    (Texas Biomedical Research Institute)

  • Colin Chuba

    (Texas Biomedical Research Institute)

  • Stephanie Earley

    (Texas Biomedical Research Institute)

  • Oscar H. Rodriguez

    (Texas Biomedical Research Institute)

  • Stephanie Davis Mdaki

    (Texas Biomedical Research Institute)

  • Katrina N. Kavelish

    (Texas Biomedical Research Institute)

  • Renee Escalona

    (Texas Biomedical Research Institute)

  • Cory R. A. Hallam

    (Texas Biomedical Research Institute)

  • Corbett Christie

    (Texas Biomedical Research Institute)

  • Jean L. Patterson

    (Texas Biomedical Research Institute)

  • Tim J. C. Anderson

    (Texas Biomedical Research Institute)

  • Ricardo Carrion

    (Texas Biomedical Research Institute)

  • Edward J. Dick

    (Texas Biomedical Research Institute)

  • Shannan Hall-Ursone

    (Texas Biomedical Research Institute)

  • Larry S. Schlesinger

    (Texas Biomedical Research Institute)

  • Xavier Alvarez

    (Texas Biomedical Research Institute)

  • Deepak Kaushal

    (Texas Biomedical Research Institute)

  • Luis D. Giavedoni

    (Texas Biomedical Research Institute)

  • Joanne Turner

    (Texas Biomedical Research Institute)

  • Luis Martinez-Sobrido

    (Texas Biomedical Research Institute)

  • Jordi B. Torrelles

    (Texas Biomedical Research Institute)

Abstract

Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.

Suggested Citation

  • Fatai S. Oladunni & Jun-Gyu Park & Paula A. Pino & Olga Gonzalez & Anwari Akhter & Anna Allué-Guardia & Angélica Olmo-Fontánez & Shalini Gautam & Andreu Garcia-Vilanova & Chengjin Ye & Kevin Chiem & C, 2020. "Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19891-7
    DOI: 10.1038/s41467-020-19891-7
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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. Weizhong Li & Tao Wang & Arunraj M. Rajendrakumar & Gyanada Acharya & Zizhen Miao & Berin P. Varghese & Hailiang Yu & Bibek Dhakal & Tanya LeRoith & Athira Karunakaran & Wenbin Tuo & Xiaoping Zhu, 2023. "An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Mengxin Luo & Jun Mo & Ziqiao Wang & Huimin Wei & Kexin Chen & Liteng Shen & Ying Wang & Linjie Li & Yongkang Chen & Weihao Chen & Xue Li & Hui Feng & Xinyu Wang & Huan Zhou & Bizhi Li & Feng Xu & Qin, 2025. "SARS-CoV-2 NSP14 inhibitor exhibits potent antiviral activity and reverses NSP14-driven host modulation," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    4. Lei Peng & Yingxia Hu & Madeleine C. Mankowski & Ping Ren & Rita E. Chen & Jin Wei & Min Zhao & Tongqing Li & Therese Tripler & Lupeng Ye & Ryan D. Chow & Zhenhao Fang & Chunxiang Wu & Matthew B. Dong, 2022. "Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    5. Francisco S. Mesquita & Laurence Abrami & Lucie Bracq & Nattawadee Panyain & Vincent Mercier & Béatrice Kunz & Audrey Chuat & Joana Carlevaro-Fita & Didier Trono & F. Gisou van der Goot, 2023. "SARS-CoV-2 hijacks a cell damage response, which induces transcription of a more efficient Spike S-acyltransferase," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Wenjuan Dong & Jing Wang & Lei Tian & Jianying Zhang & Erik W. Settles & Chao Qin & Daniel R. Steinken-Kollath & Ashley N. Itogawa & Kimberly R. Celona & Jinhee Yi & Mitchell Bryant & Heather Mead & S, 2023. "Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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