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Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2
Mice are normally unaffected by SARS coronavirus 2 (SARS-CoV-2) infection since the virus does not bind effectively to the murine version of the angiotensin-converting enzyme 2 (ACE2) receptor molecule. Here, we report that induced mild pulmonary morbidities rendered SARS-CoV-2–refractive CD-1 mice...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262502/ https://www.ncbi.nlm.nih.gov/pubmed/33974566 http://dx.doi.org/10.1172/jci.insight.145916 |
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author | Falach, Reut Bar-On, Liat Lazar, Shlomi Kadar, Tamar Mazor, Ohad Aftalion, Moshe Gur, David Evgy, Yentl Shifman, Ohad Aminov, Tamar Israeli, Ofir Cohen-Gihon, Inbar Zaide, Galia Gutman, Hila Vagima, Yaron Makdasi, Efi Stein, Dana Rosenfeld, Ronit Alcalay, Ron Zahavy, Eran Levy, Haim Glinert, Itai Ben-Shmuel, Amir Israely, Tomer Melamed, Sharon Politi, Boaz Achdout, Hagit Yitzhaki, Shmuel Kronman, Chanoch Sabo, Tamar |
author_facet | Falach, Reut Bar-On, Liat Lazar, Shlomi Kadar, Tamar Mazor, Ohad Aftalion, Moshe Gur, David Evgy, Yentl Shifman, Ohad Aminov, Tamar Israeli, Ofir Cohen-Gihon, Inbar Zaide, Galia Gutman, Hila Vagima, Yaron Makdasi, Efi Stein, Dana Rosenfeld, Ronit Alcalay, Ron Zahavy, Eran Levy, Haim Glinert, Itai Ben-Shmuel, Amir Israely, Tomer Melamed, Sharon Politi, Boaz Achdout, Hagit Yitzhaki, Shmuel Kronman, Chanoch Sabo, Tamar |
author_sort | Falach, Reut |
collection | PubMed |
description | Mice are normally unaffected by SARS coronavirus 2 (SARS-CoV-2) infection since the virus does not bind effectively to the murine version of the angiotensin-converting enzyme 2 (ACE2) receptor molecule. Here, we report that induced mild pulmonary morbidities rendered SARS-CoV-2–refractive CD-1 mice susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low doses of the acute lung injury stimulants bleomycin or ricin caused severe disease in CD-1 mice, manifested by sustained body weight loss and mortality rates greater than 50%. Further studies revealed markedly higher levels of viral RNA in the lungs, heart, and serum of low-dose ricin–pretreated mice compared with non-pretreated mice. Furthermore, lung extracts prepared 2–3 days after viral infection contained subgenomic mRNA and virus particles capable of replication only when derived from the pretreated mice. The deleterious effects of SARS-CoV-2 infection were effectively alleviated by passive transfer of polyclonal or monoclonal antibodies generated against the SARS-CoV-2 receptor binding domain (RBD). Thus, viral cell entry in the sensitized mice seems to depend on viral RBD binding, albeit by a mechanism other than the canonical ACE2-mediated uptake route. This unique mode of viral entry, observed over a mildly injured tissue background, may contribute to the exacerbation of coronavirus disease 2019 (COVID-19) pathologies in patients with preexisting morbidities. |
format | Online Article Text |
id | pubmed-8262502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-82625022021-07-13 Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2 Falach, Reut Bar-On, Liat Lazar, Shlomi Kadar, Tamar Mazor, Ohad Aftalion, Moshe Gur, David Evgy, Yentl Shifman, Ohad Aminov, Tamar Israeli, Ofir Cohen-Gihon, Inbar Zaide, Galia Gutman, Hila Vagima, Yaron Makdasi, Efi Stein, Dana Rosenfeld, Ronit Alcalay, Ron Zahavy, Eran Levy, Haim Glinert, Itai Ben-Shmuel, Amir Israely, Tomer Melamed, Sharon Politi, Boaz Achdout, Hagit Yitzhaki, Shmuel Kronman, Chanoch Sabo, Tamar JCI Insight Research Article Mice are normally unaffected by SARS coronavirus 2 (SARS-CoV-2) infection since the virus does not bind effectively to the murine version of the angiotensin-converting enzyme 2 (ACE2) receptor molecule. Here, we report that induced mild pulmonary morbidities rendered SARS-CoV-2–refractive CD-1 mice susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low doses of the acute lung injury stimulants bleomycin or ricin caused severe disease in CD-1 mice, manifested by sustained body weight loss and mortality rates greater than 50%. Further studies revealed markedly higher levels of viral RNA in the lungs, heart, and serum of low-dose ricin–pretreated mice compared with non-pretreated mice. Furthermore, lung extracts prepared 2–3 days after viral infection contained subgenomic mRNA and virus particles capable of replication only when derived from the pretreated mice. The deleterious effects of SARS-CoV-2 infection were effectively alleviated by passive transfer of polyclonal or monoclonal antibodies generated against the SARS-CoV-2 receptor binding domain (RBD). Thus, viral cell entry in the sensitized mice seems to depend on viral RBD binding, albeit by a mechanism other than the canonical ACE2-mediated uptake route. This unique mode of viral entry, observed over a mildly injured tissue background, may contribute to the exacerbation of coronavirus disease 2019 (COVID-19) pathologies in patients with preexisting morbidities. American Society for Clinical Investigation 2021-06-22 /pmc/articles/PMC8262502/ /pubmed/33974566 http://dx.doi.org/10.1172/jci.insight.145916 Text en © 2021 Falach et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Falach, Reut Bar-On, Liat Lazar, Shlomi Kadar, Tamar Mazor, Ohad Aftalion, Moshe Gur, David Evgy, Yentl Shifman, Ohad Aminov, Tamar Israeli, Ofir Cohen-Gihon, Inbar Zaide, Galia Gutman, Hila Vagima, Yaron Makdasi, Efi Stein, Dana Rosenfeld, Ronit Alcalay, Ron Zahavy, Eran Levy, Haim Glinert, Itai Ben-Shmuel, Amir Israely, Tomer Melamed, Sharon Politi, Boaz Achdout, Hagit Yitzhaki, Shmuel Kronman, Chanoch Sabo, Tamar Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2 |
title | Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2 |
title_full | Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2 |
title_fullStr | Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2 |
title_full_unstemmed | Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2 |
title_short | Mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to SARS-CoV-2 |
title_sort | mice with induced pulmonary morbidities display severe lung inflammation and mortality following exposure to sars-cov-2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262502/ https://www.ncbi.nlm.nih.gov/pubmed/33974566 http://dx.doi.org/10.1172/jci.insight.145916 |
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