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

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, Christine Tait-Burkard, Sarah Fletcher, Stephen Anderson, Sharon Brown, Louise Gibbard, Thomas Tzelos, Dawn MacMillan-Christensen, J. Kenneth Baillie, David A. Dorward, David J. Griffiths () and Finn Grey ()
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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
David A. Dorward: Queen’s Medical Research Institute
David J. Griffiths: Moredun Research Institute
Finn Grey: University of Edinburgh

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-024-54615-1

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