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Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease

Author

Listed:
  • Long Fung Chau

    (University of Edinburgh)

  • Simon Lillico

    (University of Edinburgh)

  • Tanja Opriessnig

    (Moredun Research Institute)

  • Rosemary Blake

    (University of Edinburgh)

  • Luc Tardy

    (University of Edinburgh)

  • Chen-Hsuin Lee

    (University of Edinburgh)

  • Scott Maxwell

    (University of Edinburgh)

  • Claire Warren

    (University of Edinburgh)

  • Elizabeth Thornton

    (University of Edinburgh)

  • Catherine L. Mclaughlin

    (University of Edinburgh)

  • Gerry McLachlan

    (University of Edinburgh)

  • Christine Tait-Burkard

    (University of Edinburgh)

  • Sarah Fletcher

    (University of Edinburgh)

  • Stephen Anderson

    (Moredun Research Institute)

  • Sharon Brown

    (Moredun Research Institute)

  • Louise Gibbard

    (Moredun Research Institute)

  • Thomas Tzelos

    (Moredun Research Institute)

  • Dawn MacMillan-Christensen

    (Moredun Research Institute)

  • J. Kenneth Baillie

    (University of Edinburgh
    University of Edinburgh)

  • David A. Dorward

    (Queen’s Medical Research Institute
    Royal Infirmary)

  • David J. Griffiths

    (Moredun Research Institute)

  • Finn Grey

    (University of Edinburgh)

Abstract

Animal models that accurately reflect COVID-19 are vital for understanding mechanisms of disease and advancing development of improved vaccines and therapeutics. Pigs are increasingly recognized as valuable models for human disease due to their genetic, anatomical, physiological, and immunological similarities to humans, and they present a more ethically viable alternative to non-human primates. However, pigs are not susceptible to SARS-CoV-2 infection which limits their utility as a model. To address this, we have developed transgenic pigs expressing human ACE2 that are susceptible to SARS-CoV-2 infection. Following challenge, clinical signs consistent with COVID-19, including fever, coughing and respiratory distress were observed, with virus replication detected in the nasal turbinates, trachea and lungs up to the study endpoint, seven days post-infection. Notably, examination of tissues revealed immunopathology in the lungs consistent with histological changes observed in fatal human COVID-19 cases. This study establishes human ACE2 transgenic pigs as a large animal model that accurately reflects many aspects of COVID-19 disease.

Suggested Citation

  • Long Fung Chau & Simon Lillico & Tanja Opriessnig & Rosemary Blake & Luc Tardy & Chen-Hsuin Lee & Scott Maxwell & Claire Warren & Elizabeth Thornton & Catherine L. Mclaughlin & Gerry McLachlan & Chris, 2025. "Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-54615-1
    DOI: 10.1038/s41467-024-54615-1
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    References listed on IDEAS

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