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Volume 10
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10.3390/pathogens10070824
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Article

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

by
Nora M. Gerhards
1,*,
Jan B. W. J. Cornelissen
1,
Lucien J. M. van Keulen
1,
José Harders-Westerveen
1,
Rianka Vloet
1,
Bregtje Smid
1,
Stéphanie Vastenhouw
1,
Sophie van Oort
1,
Renate W. Hakze-van der Honing
1,
Jose L. Gonzales
1,
Norbert Stockhofe-Zurwieden
1,
Rineke de Jong
1,
Wim H. M. van der Poel
1,
Sandra Vreman
1,
Jeroen Kortekaas
1,2,
Paul J. Wichgers Schreur
1 and
Nadia Oreshkova
1,*
1
Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands
2
Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands
*
Authors to whom correspondence should be addressed.
Pathogens 2021, 10(7), 824; https://doi.org/10.3390/pathogens10070824
Submission received: 8 May 2021 / Revised: 20 June 2021 / Accepted: 27 June 2021 / Published: 30 June 2021
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Abstract

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.
Keywords: SARS-CoV-2; hamster model; precision-cut lung slices; activity; histology scores SARS-CoV-2; hamster model; precision-cut lung slices; activity; histology scores

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MDPI and ACS Style

Gerhards, N.M.; Cornelissen, J.B.W.J.; van Keulen, L.J.M.; Harders-Westerveen, J.; Vloet, R.; Smid, B.; Vastenhouw, S.; van Oort, S.; Hakze-van der Honing, R.W.; Gonzales, J.L.; et al. 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. Pathogens 2021, 10, 824. https://doi.org/10.3390/pathogens10070824

AMA Style

Gerhards NM, Cornelissen JBWJ, van Keulen LJM, Harders-Westerveen J, Vloet R, Smid B, Vastenhouw S, van Oort S, Hakze-van der Honing RW, Gonzales JL, et al. 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. Pathogens. 2021; 10(7):824. https://doi.org/10.3390/pathogens10070824

Chicago/Turabian Style

Gerhards, Nora M., Jan B. W. J. Cornelissen, Lucien J. M. van Keulen, José Harders-Westerveen, Rianka Vloet, Bregtje Smid, Stéphanie Vastenhouw, Sophie van Oort, Renate W. Hakze-van der Honing, Jose L. Gonzales, and et al. 2021. "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" Pathogens 10, no. 7: 824. https://doi.org/10.3390/pathogens10070824

APA Style

Gerhards, N. M., Cornelissen, J. B. W. J., van Keulen, L. J. M., Harders-Westerveen, J., Vloet, R., Smid, B., Vastenhouw, S., van Oort, S., Hakze-van der Honing, R. W., Gonzales, J. L., Stockhofe-Zurwieden, N., de Jong, R., van der Poel, W. H. M., Vreman, S., Kortekaas, J., Wichgers Schreur, P. J., & Oreshkova, N. (2021). 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. Pathogens, 10(7), 824. https://doi.org/10.3390/pathogens10070824

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