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Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model

In assessing species susceptibility for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the search for an appropriate animal model, multiple research groups around the world inoculated a broad range of animal species using various SARS-CoV-2 strains, doses and administration rou...

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Autores principales: Gerhards, Nora M., Cornelissen, Jan B. W. J., van Keulen, Lucien J. M., Harders-Westerveen, José, Vloet, Rianka, Smid, Bregtje, Vastenhouw, Stéphanie, van Oort, Sophie, Hakze-van der Honing, Renate W., Gonzales, Jose L., Stockhofe-Zurwieden, Norbert, de Jong, Rineke, van der Poel, Wim H. M., Vreman, Sandra, Kortekaas, Jeroen, Wichgers Schreur, Paul J., Oreshkova, Nadia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308566/
https://www.ncbi.nlm.nih.gov/pubmed/34209230
http://dx.doi.org/10.3390/pathogens10070824
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author Gerhards, Nora M.
Cornelissen, Jan B. W. J.
van Keulen, Lucien J. M.
Harders-Westerveen, José
Vloet, Rianka
Smid, Bregtje
Vastenhouw, Stéphanie
van Oort, Sophie
Hakze-van der Honing, Renate W.
Gonzales, Jose L.
Stockhofe-Zurwieden, Norbert
de Jong, Rineke
van der Poel, Wim H. M.
Vreman, Sandra
Kortekaas, Jeroen
Wichgers Schreur, Paul J.
Oreshkova, Nadia
author_facet Gerhards, Nora M.
Cornelissen, Jan B. W. J.
van Keulen, Lucien J. M.
Harders-Westerveen, José
Vloet, Rianka
Smid, Bregtje
Vastenhouw, Stéphanie
van Oort, Sophie
Hakze-van der Honing, Renate W.
Gonzales, Jose L.
Stockhofe-Zurwieden, Norbert
de Jong, Rineke
van der Poel, Wim H. M.
Vreman, Sandra
Kortekaas, Jeroen
Wichgers Schreur, Paul J.
Oreshkova, Nadia
author_sort Gerhards, Nora M.
collection PubMed
description In assessing species susceptibility for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the search for an appropriate animal model, multiple research groups around the world inoculated a broad range of animal species using various SARS-CoV-2 strains, doses and administration routes. Although in silico analyses based on receptor binding and diverse in vitro cell cultures were valuable, exact prediction of species susceptibility based on these tools proved challenging. Here, we assessed whether precision-cut lung slices (PCLS) could facilitate the selection of animal models, thereby reducing animal experimentation. Pig, hamster and cat PCLS were incubated with SARS-CoV-2 and virus replication was followed over time. Virus replicated efficiently in PCLS from hamsters and cats, while no evidence of replication was obtained for pig PCLS. These data corroborate the findings of many research groups that have investigated the susceptibility of hamsters, pigs and cats towards infection with SARS-CoV-2. Our findings suggest that PCLS can be used as convenient tool for the screening of different animal species for sensitivity to newly emerged viruses. To validate our results obtained in PCLS, we employed the hamster model. Hamsters were inoculated with SARS-CoV-2 via the intranasal route. Susceptibility to infection was evaluated by body weight loss, viral loads in oropharyngeal swabs and respiratory tissues and lung pathology. The broadly used hamster model was further refined by including activity tracking of the hamsters by an activity wheel as a very robust and sensitive parameter for clinical health. In addition, to facilitate the quantification of pathology in the lungs, we devised a semi-quantitative scoring system for evaluating the degree of histological changes in the lungs. The inclusion of these additional parameters refined and enriched the hamster model, allowing for the generation of more data from a single experiment.
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spelling pubmed-83085662021-07-25 Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model Gerhards, Nora M. Cornelissen, Jan B. W. J. van Keulen, Lucien J. M. Harders-Westerveen, José Vloet, Rianka Smid, Bregtje Vastenhouw, Stéphanie van Oort, Sophie Hakze-van der Honing, Renate W. Gonzales, Jose L. Stockhofe-Zurwieden, Norbert de Jong, Rineke van der Poel, Wim H. M. Vreman, Sandra Kortekaas, Jeroen Wichgers Schreur, Paul J. Oreshkova, Nadia Pathogens Article In assessing species susceptibility for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the search for an appropriate animal model, multiple research groups around the world inoculated a broad range of animal species using various SARS-CoV-2 strains, doses and administration routes. Although in silico analyses based on receptor binding and diverse in vitro cell cultures were valuable, exact prediction of species susceptibility based on these tools proved challenging. Here, we assessed whether precision-cut lung slices (PCLS) could facilitate the selection of animal models, thereby reducing animal experimentation. Pig, hamster and cat PCLS were incubated with SARS-CoV-2 and virus replication was followed over time. Virus replicated efficiently in PCLS from hamsters and cats, while no evidence of replication was obtained for pig PCLS. These data corroborate the findings of many research groups that have investigated the susceptibility of hamsters, pigs and cats towards infection with SARS-CoV-2. Our findings suggest that PCLS can be used as convenient tool for the screening of different animal species for sensitivity to newly emerged viruses. To validate our results obtained in PCLS, we employed the hamster model. Hamsters were inoculated with SARS-CoV-2 via the intranasal route. Susceptibility to infection was evaluated by body weight loss, viral loads in oropharyngeal swabs and respiratory tissues and lung pathology. The broadly used hamster model was further refined by including activity tracking of the hamsters by an activity wheel as a very robust and sensitive parameter for clinical health. In addition, to facilitate the quantification of pathology in the lungs, we devised a semi-quantitative scoring system for evaluating the degree of histological changes in the lungs. The inclusion of these additional parameters refined and enriched the hamster model, allowing for the generation of more data from a single experiment. MDPI 2021-06-30 /pmc/articles/PMC8308566/ /pubmed/34209230 http://dx.doi.org/10.3390/pathogens10070824 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gerhards, Nora M.
Cornelissen, Jan B. W. J.
van Keulen, Lucien J. M.
Harders-Westerveen, José
Vloet, Rianka
Smid, Bregtje
Vastenhouw, Stéphanie
van Oort, Sophie
Hakze-van der Honing, Renate W.
Gonzales, Jose L.
Stockhofe-Zurwieden, Norbert
de Jong, Rineke
van der Poel, Wim H. M.
Vreman, Sandra
Kortekaas, Jeroen
Wichgers Schreur, Paul J.
Oreshkova, Nadia
Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model
title Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model
title_full Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model
title_fullStr Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model
title_full_unstemmed Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model
title_short Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model
title_sort predictive value of precision-cut lung slices for the susceptibility of three animal species for sars-cov-2 and validation in a refined hamster model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308566/
https://www.ncbi.nlm.nih.gov/pubmed/34209230
http://dx.doi.org/10.3390/pathogens10070824
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