IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-19891-7.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-19891-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-19891-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. 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.
    4. 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.
    5. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19891-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.