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3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract

View ORCID ProfileLuca M. Zaeck, View ORCID ProfileDavid Scheibner, View ORCID ProfileJulia Sehl, View ORCID ProfileMartin Müller, View ORCID ProfileDonata Hoffmann, View ORCID ProfileMartin Beer, View ORCID ProfileElsayed M. Abdelwhab, View ORCID ProfileThomas C. Mettenleiter, View ORCID ProfileAngele Breithaupt, View ORCID ProfileStefan Finke
doi: https://doi.org/10.1101/2020.10.17.339051
Luca M. Zaeck
1Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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David Scheibner
1Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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Julia Sehl
2Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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Martin Müller
1Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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Donata Hoffmann
3Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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Martin Beer
3Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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Elsayed M. Abdelwhab
1Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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Thomas C. Mettenleiter
4Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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Angele Breithaupt
2Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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Stefan Finke
1Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald, Isle of Riems, Germany
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  • For correspondence: stefan.finke@fli.de
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Abstract

The visualization of viral pathogens in infected tissues is an invaluable tool to understand spatial virus distribution, localization, and cell tropism in vivo. Commonly, virus-infected tissues are analyzed using conventional immunohistochemistry in paraffin-embedded thin sections. Here, we demonstrate the utility of volumetric three-dimensional (3D) immunofluorescence imaging using tissue optical clearing and light sheet microscopy to investigate host-pathogen interactions of pandemic SARS-CoV-2 in ferrets at a mesoscopic scale. The superior spatial context of large, intact samples (> 150 mm3) allowed detailed quantification of interrelated parameters like focus-to-focus distance or SARS-CoV-2-infected area, facilitating an in-depth description of SARS-CoV-2 infection foci. Accordingly, we could confirm a preferential infection of the ferret upper respiratory tract by SARS-CoV-2 and emphasize a distinct focal infection pattern in nasal turbinates. Conclusively, we present a proof-of-concept study for investigating critically important respiratory pathogens in their spatial tissue morphology and demonstrate the first specific 3D visualization of SARS-CoV-2 infection.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 18, 2020.
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3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract
Luca M. Zaeck, David Scheibner, Julia Sehl, Martin Müller, Donata Hoffmann, Martin Beer, Elsayed M. Abdelwhab, Thomas C. Mettenleiter, Angele Breithaupt, Stefan Finke
bioRxiv 2020.10.17.339051; doi: https://doi.org/10.1101/2020.10.17.339051
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3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract
Luca M. Zaeck, David Scheibner, Julia Sehl, Martin Müller, Donata Hoffmann, Martin Beer, Elsayed M. Abdelwhab, Thomas C. Mettenleiter, Angele Breithaupt, Stefan Finke
bioRxiv 2020.10.17.339051; doi: https://doi.org/10.1101/2020.10.17.339051

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