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Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate.(1–3) Due to the urgency of this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety and efficacy st...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302201/ https://www.ncbi.nlm.nih.gov/pubmed/32577647 http://dx.doi.org/10.1101/2020.05.27.118893 |
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author | Israelow, Benjamin Song, Eric Mao, Tianyang Lu, Peiwen Meir, Amit Liu, Feimei Alfajaro, Mia Madel Wei, Jin Dong, Huiping Homer, Robert J Ring, Aaron Wilen, Craig B Iwasaki, Akiko |
author_facet | Israelow, Benjamin Song, Eric Mao, Tianyang Lu, Peiwen Meir, Amit Liu, Feimei Alfajaro, Mia Madel Wei, Jin Dong, Huiping Homer, Robert J Ring, Aaron Wilen, Craig B Iwasaki, Akiko |
author_sort | Israelow, Benjamin |
collection | PubMed |
description | Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate.(1–3) Due to the urgency of this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety and efficacy studies.(4) Laboratory mice have been the stalwart of these types of studies; however, they do not support infection by SARS-CoV-2 due to the inability of its spike (S) protein to engage the mouse ortholog of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis,(5) these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno associated virus (AAV)-mediated expression of hACE2. These mice support viral replication and antibody production and exhibit pathologic findings found in COVID-19 patients as well as non-human primate models. Moreover, we show that type I interferons are unable to control SARS-CoV2 replication and drive pathologic responses. Thus, the hACE2-AAV mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds. This represents a much-needed platform for rapidly testing prophylactic and therapeutic strategies to combat COVID-19. |
format | Online Article Text |
id | pubmed-7302201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-73022012020-06-23 Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling Israelow, Benjamin Song, Eric Mao, Tianyang Lu, Peiwen Meir, Amit Liu, Feimei Alfajaro, Mia Madel Wei, Jin Dong, Huiping Homer, Robert J Ring, Aaron Wilen, Craig B Iwasaki, Akiko bioRxiv Article Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate.(1–3) Due to the urgency of this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety and efficacy studies.(4) Laboratory mice have been the stalwart of these types of studies; however, they do not support infection by SARS-CoV-2 due to the inability of its spike (S) protein to engage the mouse ortholog of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis,(5) these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno associated virus (AAV)-mediated expression of hACE2. These mice support viral replication and antibody production and exhibit pathologic findings found in COVID-19 patients as well as non-human primate models. Moreover, we show that type I interferons are unable to control SARS-CoV2 replication and drive pathologic responses. Thus, the hACE2-AAV mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds. This represents a much-needed platform for rapidly testing prophylactic and therapeutic strategies to combat COVID-19. Cold Spring Harbor Laboratory 2020-05-27 /pmc/articles/PMC7302201/ /pubmed/32577647 http://dx.doi.org/10.1101/2020.05.27.118893 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/It is made available under a CC-BY-NC-ND 4.0 International license (http://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Article Israelow, Benjamin Song, Eric Mao, Tianyang Lu, Peiwen Meir, Amit Liu, Feimei Alfajaro, Mia Madel Wei, Jin Dong, Huiping Homer, Robert J Ring, Aaron Wilen, Craig B Iwasaki, Akiko Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling |
title | Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling |
title_full | Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling |
title_fullStr | Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling |
title_full_unstemmed | Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling |
title_short | Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling |
title_sort | mouse model of sars-cov-2 reveals inflammatory role of type i interferon signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302201/ https://www.ncbi.nlm.nih.gov/pubmed/32577647 http://dx.doi.org/10.1101/2020.05.27.118893 |
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