Journal Article

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

Baillie, J. Kenneth, Lillico, Simon, Warren, Claire, Lee, Chen-Hsuin, Anderson, Stephen, Mclaughlin, Catherine L., Fletcher, Sarah, Blake, Rosemary, Grey, Finn, Maxwell, Scott, Griffiths, David J., Brown, Sharon, MacMillan-Christensen, Dawn, Thornton, Elizabeth, Tzelos, Thomas, Tait-Burkard, Christine, Chau, Long Fung, Opriessnig, Tanja, McLachlan, Gerry, Tardy, Luc, Dorward, David A., Gibbard, Louise

2025

Overview

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. Long Fung Chau and colleagues report the generation of transgenic pigs expressing human ACE2, and show that they exhibit clinical signs and immunopathology consistent with COVID-19 following infection with SARS-CoV-2, suggesting that human ACE2 transgenic pigs are a viable large animal model for COVID-19.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/35 / 38 / 38/77 / 631/326/596/4130 / 631/61/17/1511 / 692/308/1426 / 692/420/254 / ACE2 / Angiotensin-converting enzyme 2 / Angiotensin-Converting Enzyme 2 - genetics / Angiotensin-Converting Enzyme 2 - metabolism / Animal diseases / Animal models / Animals / Animals, Genetically Modified / COVID-19 / COVID-19 - genetics / COVID-19 - immunology / COVID-19 - pathology / COVID-19 - virology / Disease Models, Animal / Drug development / Humanities and Social Sciences / Humans / Immunology / Infections / Lung - pathology / Lung - virology / Lungs / multidisciplinary / Nose / SARS-CoV-2 - physiology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Swine / Trachea / Transgenic animals / Viral diseases / Virus Replication