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Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2
The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global health emergency. While most human disease is mild to moderate, some infections lead to a severe disease characterized by acute respiratory distress, hypoxia, anosmia, ageusia, and, in some insta...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787465/ https://www.ncbi.nlm.nih.gov/pubmed/35073750 http://dx.doi.org/10.1128/mbio.02906-21 |
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author | Golden, Joseph W. Li, Rong Cline, Curtis R. Zeng, Xiankun Mucker, Eric M. Fuentes-Lao, Amadeo J. Spik, Kristin W. Williams, Janice A. Twenhafel, Nancy Davis, Neil Moore, Joshua L. Stevens, Stephen Blue, Eugene Garrison, Aura R. Larson, Deanna D. Stewart, Rebekah Kunzler, Madelyn Liu, Yanan Wang, Zhongde Hooper, Jay W. |
author_facet | Golden, Joseph W. Li, Rong Cline, Curtis R. Zeng, Xiankun Mucker, Eric M. Fuentes-Lao, Amadeo J. Spik, Kristin W. Williams, Janice A. Twenhafel, Nancy Davis, Neil Moore, Joshua L. Stevens, Stephen Blue, Eugene Garrison, Aura R. Larson, Deanna D. Stewart, Rebekah Kunzler, Madelyn Liu, Yanan Wang, Zhongde Hooper, Jay W. |
author_sort | Golden, Joseph W. |
collection | PubMed |
description | The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global health emergency. While most human disease is mild to moderate, some infections lead to a severe disease characterized by acute respiratory distress, hypoxia, anosmia, ageusia, and, in some instances, neurological involvement. Small-animal models reproducing severe disease, including neurological sequela, are needed to characterize the pathophysiological mechanism(s) of disease and to identify medical countermeasures. Transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE2) viral receptor under the control of the K18 promoter develop severe and lethal respiratory disease subsequent to SARS-CoV-2 intranasal challenge when high viral doses are used. Here, we report on SARS-CoV-2 infection of hamsters engineered to express the hACE2 receptor under the control of the K18 promoter. K18-hACE2 hamsters infected with a relatively low dose of 100 or 1,000 PFU of SARS-CoV-2 developed a severe and lethal disease, with most animals succumbing by day 5 postinfection. Hamsters developed severe lesions and inflammation within the upper and lower respiratory system, including infection of the nasal cavities causing marked destruction of the olfactory epithelium as well as severe bronchopneumonia that extended deep into the alveoli. Additionally, SARS-CoV-2 infection spread to the central nervous system (CNS), including the brain stem and spinal cord. Wild-type (WT) hamsters naturally support SARS-CoV-2 infection, with the primary lesions present in the respiratory tract and nasal cavity. Overall, infection in the K18-hACE2 hamsters is more extensive than that in WT hamsters, with more CNS involvement and a lethal outcome. These findings demonstrate the K18-hACE2 hamster model will be valuable for studying SARS-CoV-2. |
format | Online Article Text |
id | pubmed-8787465 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-87874652022-02-07 Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2 Golden, Joseph W. Li, Rong Cline, Curtis R. Zeng, Xiankun Mucker, Eric M. Fuentes-Lao, Amadeo J. Spik, Kristin W. Williams, Janice A. Twenhafel, Nancy Davis, Neil Moore, Joshua L. Stevens, Stephen Blue, Eugene Garrison, Aura R. Larson, Deanna D. Stewart, Rebekah Kunzler, Madelyn Liu, Yanan Wang, Zhongde Hooper, Jay W. mBio Research Article The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global health emergency. While most human disease is mild to moderate, some infections lead to a severe disease characterized by acute respiratory distress, hypoxia, anosmia, ageusia, and, in some instances, neurological involvement. Small-animal models reproducing severe disease, including neurological sequela, are needed to characterize the pathophysiological mechanism(s) of disease and to identify medical countermeasures. Transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE2) viral receptor under the control of the K18 promoter develop severe and lethal respiratory disease subsequent to SARS-CoV-2 intranasal challenge when high viral doses are used. Here, we report on SARS-CoV-2 infection of hamsters engineered to express the hACE2 receptor under the control of the K18 promoter. K18-hACE2 hamsters infected with a relatively low dose of 100 or 1,000 PFU of SARS-CoV-2 developed a severe and lethal disease, with most animals succumbing by day 5 postinfection. Hamsters developed severe lesions and inflammation within the upper and lower respiratory system, including infection of the nasal cavities causing marked destruction of the olfactory epithelium as well as severe bronchopneumonia that extended deep into the alveoli. Additionally, SARS-CoV-2 infection spread to the central nervous system (CNS), including the brain stem and spinal cord. Wild-type (WT) hamsters naturally support SARS-CoV-2 infection, with the primary lesions present in the respiratory tract and nasal cavity. Overall, infection in the K18-hACE2 hamsters is more extensive than that in WT hamsters, with more CNS involvement and a lethal outcome. These findings demonstrate the K18-hACE2 hamster model will be valuable for studying SARS-CoV-2. American Society for Microbiology 2022-01-25 /pmc/articles/PMC8787465/ /pubmed/35073750 http://dx.doi.org/10.1128/mbio.02906-21 Text en https://doi.org/10.1128/AuthorWarrantyLicense.v1This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. |
spellingShingle | Research Article Golden, Joseph W. Li, Rong Cline, Curtis R. Zeng, Xiankun Mucker, Eric M. Fuentes-Lao, Amadeo J. Spik, Kristin W. Williams, Janice A. Twenhafel, Nancy Davis, Neil Moore, Joshua L. Stevens, Stephen Blue, Eugene Garrison, Aura R. Larson, Deanna D. Stewart, Rebekah Kunzler, Madelyn Liu, Yanan Wang, Zhongde Hooper, Jay W. Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2 |
title | Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2 |
title_full | Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2 |
title_fullStr | Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2 |
title_full_unstemmed | Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2 |
title_short | Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2 |
title_sort | hamsters expressing human angiotensin-converting enzyme 2 develop severe disease following exposure to sars-cov-2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787465/ https://www.ncbi.nlm.nih.gov/pubmed/35073750 http://dx.doi.org/10.1128/mbio.02906-21 |
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