Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease
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 immuno...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54615-1 |
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| author | 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 Finn Grey |
| author_facet | 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 Finn Grey |
| author_sort | Long Fung Chau |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-220f8661bc3f4356b90c5f01f6558ea4 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-220f8661bc3f4356b90c5f01f6558ea42025-01-19T12:31:11ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-024-54615-1Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like diseaseLong Fung Chau0Simon Lillico1Tanja Opriessnig2Rosemary Blake3Luc Tardy4Chen-Hsuin Lee5Scott Maxwell6Claire Warren7Elizabeth Thornton8Catherine L. Mclaughlin9Gerry McLachlan10Christine Tait-Burkard11Sarah Fletcher12Stephen Anderson13Sharon Brown14Louise Gibbard15Thomas Tzelos16Dawn MacMillan-Christensen17J. Kenneth Baillie18David A. Dorward19David J. Griffiths20Finn Grey21Roslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghMoredun Research InstituteRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghMoredun Research InstituteMoredun Research InstituteMoredun Research InstituteMoredun Research InstituteMoredun Research InstituteRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghCentre for Inflammation Research, Queen’s Medical Research InstituteMoredun Research InstituteRoslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghAbstract 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.https://doi.org/10.1038/s41467-024-54615-1 |
| spellingShingle | 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 Finn Grey Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease Nature Communications |
| title | Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease |
| title_full | Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease |
| title_fullStr | Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease |
| title_full_unstemmed | Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease |
| title_short | Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease |
| title_sort | human ace2 transgenic pigs are susceptible to sars cov 2 and develop covid 19 like disease |
| url | https://doi.org/10.1038/s41467-024-54615-1 |
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