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Article

Light Sheet Microscopy-Assisted 3D Analysis of SARS-CoV-2 Infection in the Respiratory Tract of the Ferret Model

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Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany
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Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany
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Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany
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Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Fasséli Coulibaly
Viruses 2021, 13(3), 529; https://doi.org/10.3390/v13030529
Received: 23 February 2021 / Revised: 4 March 2021 / Accepted: 19 March 2021 / Published: 23 March 2021
(This article belongs to the Special Issue Voyages through the Multiple Scales of Virus Biology)
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 suggest clustering of infection foci in close proximity. 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. View Full-Text
Keywords: SARS-CoV-2; COVID-19; 3D immunofluorescence; light sheet microscopy; confocal laser scanning microscopy; tissue optical clearing; host–pathogen interactions; respiratory tract infection SARS-CoV-2; COVID-19; 3D immunofluorescence; light sheet microscopy; confocal laser scanning microscopy; tissue optical clearing; host–pathogen interactions; respiratory tract infection
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MDPI and ACS Style

Zaeck, L.M.; Scheibner, D.; Sehl, J.; Müller, M.; Hoffmann, D.; Beer, M.; Abdelwhab, E.M.; Mettenleiter, T.C.; Breithaupt, A.; Finke, S. Light Sheet Microscopy-Assisted 3D Analysis of SARS-CoV-2 Infection in the Respiratory Tract of the Ferret Model. Viruses 2021, 13, 529. https://doi.org/10.3390/v13030529

AMA Style

Zaeck LM, Scheibner D, Sehl J, Müller M, Hoffmann D, Beer M, Abdelwhab EM, Mettenleiter TC, Breithaupt A, Finke S. Light Sheet Microscopy-Assisted 3D Analysis of SARS-CoV-2 Infection in the Respiratory Tract of the Ferret Model. Viruses. 2021; 13(3):529. https://doi.org/10.3390/v13030529

Chicago/Turabian Style

Zaeck, Luca M.; Scheibner, David; Sehl, Julia; Müller, Martin; Hoffmann, Donata; Beer, Martin; Abdelwhab, Elsayed M.; Mettenleiter, Thomas C.; Breithaupt, Angele; Finke, Stefan. 2021. "Light Sheet Microscopy-Assisted 3D Analysis of SARS-CoV-2 Infection in the Respiratory Tract of the Ferret Model" Viruses 13, no. 3: 529. https://doi.org/10.3390/v13030529

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