Cargando…

Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and und...

Descripción completa

Detalles Bibliográficos
Autores principales: Rathnasinghe, Raveen, Strohmeier, Shirin, Amanat, Fatima, Gillespie, Virginia L., Krammer, Florian, García-Sastre, Adolfo, Coughlan, Lynda, Schotsaert, Michael, Uccellini, Melissa B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655046/
https://www.ncbi.nlm.nih.gov/pubmed/33073694
http://dx.doi.org/10.1080/22221751.2020.1838955
_version_ 1783608157933666304
author Rathnasinghe, Raveen
Strohmeier, Shirin
Amanat, Fatima
Gillespie, Virginia L.
Krammer, Florian
García-Sastre, Adolfo
Coughlan, Lynda
Schotsaert, Michael
Uccellini, Melissa B.
author_facet Rathnasinghe, Raveen
Strohmeier, Shirin
Amanat, Fatima
Gillespie, Virginia L.
Krammer, Florian
García-Sastre, Adolfo
Coughlan, Lynda
Schotsaert, Michael
Uccellini, Melissa B.
author_sort Rathnasinghe, Raveen
collection PubMed
description Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2) [1–3]. Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection. The K18-hACE2 model provides a stringent model for testing vaccines and antivirals, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.
format Online
Article
Text
id pubmed-7655046
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-76550462020-11-19 Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection Rathnasinghe, Raveen Strohmeier, Shirin Amanat, Fatima Gillespie, Virginia L. Krammer, Florian García-Sastre, Adolfo Coughlan, Lynda Schotsaert, Michael Uccellini, Melissa B. Emerg Microbes Infect Research Article Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2) [1–3]. Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection. The K18-hACE2 model provides a stringent model for testing vaccines and antivirals, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains. Taylor & Francis 2020-11-06 /pmc/articles/PMC7655046/ /pubmed/33073694 http://dx.doi.org/10.1080/22221751.2020.1838955 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Rathnasinghe, Raveen
Strohmeier, Shirin
Amanat, Fatima
Gillespie, Virginia L.
Krammer, Florian
García-Sastre, Adolfo
Coughlan, Lynda
Schotsaert, Michael
Uccellini, Melissa B.
Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection
title Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection
title_full Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection
title_fullStr Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection
title_full_unstemmed Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection
title_short Comparison of transgenic and adenovirus hACE2 mouse models for SARS-CoV-2 infection
title_sort comparison of transgenic and adenovirus hace2 mouse models for sars-cov-2 infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655046/
https://www.ncbi.nlm.nih.gov/pubmed/33073694
http://dx.doi.org/10.1080/22221751.2020.1838955
work_keys_str_mv AT rathnasingheraveen comparisonoftransgenicandadenovirushace2mousemodelsforsarscov2infection
AT strohmeiershirin comparisonoftransgenicandadenovirushace2mousemodelsforsarscov2infection
AT amanatfatima comparisonoftransgenicandadenovirushace2mousemodelsforsarscov2infection
AT gillespievirginial comparisonoftransgenicandadenovirushace2mousemodelsforsarscov2infection
AT krammerflorian comparisonoftransgenicandadenovirushace2mousemodelsforsarscov2infection
AT garciasastreadolfo comparisonoftransgenicandadenovirushace2mousemodelsforsarscov2infection
AT coughlanlynda comparisonoftransgenicandadenovirushace2mousemodelsforsarscov2infection
AT schotsaertmichael comparisonoftransgenicandadenovirushace2mousemodelsforsarscov2infection
AT uccellinimelissab comparisonoftransgenicandadenovirushace2mousemodelsforsarscov2infection