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Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice
The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening. Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2, which greatly limits its application in routine r...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705082/ https://www.ncbi.nlm.nih.gov/pubmed/34952899 http://dx.doi.org/10.1038/s41392-021-00851-6 |
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author | Bi, Zhenfei Hong, Weiqi Que, Haiying He, Cai Ren, Wenyan Yang, Jingyun Lu, Tianqi Chen, Li Lu, Shuaiyao Peng, Xiaozhong Wei, Xiawei |
author_facet | Bi, Zhenfei Hong, Weiqi Que, Haiying He, Cai Ren, Wenyan Yang, Jingyun Lu, Tianqi Chen, Li Lu, Shuaiyao Peng, Xiaozhong Wei, Xiawei |
author_sort | Bi, Zhenfei |
collection | PubMed |
description | The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening. Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2, which greatly limits its application in routine research. Here, we generate a mouse model of COVID-19 under a general laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) observed in humans. Briefly, human ACE2-transgenic (hACE2) mice were intratracheally instilled with the formaldehyde-inactivated SARS-CoV-2, resulting in a rapid weight loss and detrimental changes in lung structure and function. The pulmonary pathologic changes were characterized by diffuse alveolar damage with pulmonary consolidation, hemorrhage, necrotic debris, and hyaline membrane formation. The production of fatal cytokines (IL-1β, TNF-α, and IL-6) and the infiltration of activated neutrophils, inflammatory monocyte-macrophages, and T cells in the lung were also determined, suggesting the activation of an adaptive immune response. Therapeutic strategies, such as dexamethasone or passive antibody therapy, could effectively ameliorate the disease progression in this model. Therefore, the established mouse model for SARS-CoV-2-induced ARDS in the current study may provide a robust tool for researchers in the standard open laboratory to investigate the pathological mechanisms or develop new therapeutic strategies for COVID-19 and ARDS. |
format | Online Article Text |
id | pubmed-8705082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-87050822021-12-27 Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice Bi, Zhenfei Hong, Weiqi Que, Haiying He, Cai Ren, Wenyan Yang, Jingyun Lu, Tianqi Chen, Li Lu, Shuaiyao Peng, Xiaozhong Wei, Xiawei Signal Transduct Target Ther Article The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening. Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2, which greatly limits its application in routine research. Here, we generate a mouse model of COVID-19 under a general laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) observed in humans. Briefly, human ACE2-transgenic (hACE2) mice were intratracheally instilled with the formaldehyde-inactivated SARS-CoV-2, resulting in a rapid weight loss and detrimental changes in lung structure and function. The pulmonary pathologic changes were characterized by diffuse alveolar damage with pulmonary consolidation, hemorrhage, necrotic debris, and hyaline membrane formation. The production of fatal cytokines (IL-1β, TNF-α, and IL-6) and the infiltration of activated neutrophils, inflammatory monocyte-macrophages, and T cells in the lung were also determined, suggesting the activation of an adaptive immune response. Therapeutic strategies, such as dexamethasone or passive antibody therapy, could effectively ameliorate the disease progression in this model. Therefore, the established mouse model for SARS-CoV-2-induced ARDS in the current study may provide a robust tool for researchers in the standard open laboratory to investigate the pathological mechanisms or develop new therapeutic strategies for COVID-19 and ARDS. Nature Publishing Group UK 2021-12-24 /pmc/articles/PMC8705082/ /pubmed/34952899 http://dx.doi.org/10.1038/s41392-021-00851-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Bi, Zhenfei Hong, Weiqi Que, Haiying He, Cai Ren, Wenyan Yang, Jingyun Lu, Tianqi Chen, Li Lu, Shuaiyao Peng, Xiaozhong Wei, Xiawei Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice |
title | Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice |
title_full | Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice |
title_fullStr | Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice |
title_full_unstemmed | Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice |
title_short | Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice |
title_sort | inactivated sars-cov-2 induces acute respiratory distress syndrome in human ace2-transgenic mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705082/ https://www.ncbi.nlm.nih.gov/pubmed/34952899 http://dx.doi.org/10.1038/s41392-021-00851-6 |
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