Light sheet microscopy-assisted 3d analysis of sars-cov-2 infection in the respiratory tract of the ferret model

Luca M. Zaeck; David Scheibner; Julia Sehl; Martin Müller; Donata Hoffmann; Martin Beer; Elsayed M. Abdelwhab; Thomas C. Mettenleiter; Angele Breithaupt; Stefan Finke

doi:10.3390/v13030529

Light sheet microscopy-assisted 3d analysis of sars-cov-2 infection in the respiratory tract of the ferret model

Luca M. Zaeck
, David Scheibner
, Julia Sehl
, Martin Müller
, Donata Hoffmann
, Martin Beer
, Elsayed M. Abdelwhab
, Thomas C. Mettenleiter
, Angele Breithaupt
, Stefan Finke^*

^*Corresponding author for this work

Friedrich-Loeffler-Institute

Research output: Contribution to journal › Article › Academic › peer-review

21 Citations (Scopus)

13 Downloads (Pure)

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 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.

Original language	English
Article number	529
Journal	Viruses
Volume	13
Issue number	3
DOIs	https://doi.org/10.3390/v13030529
Publication status	Published - Mar 2021
Externally published	Yes

Bibliographical note

Funding Information:
The study was supported by intramural funding of the German Federal Ministry of Food and Agriculture provided to the Friedrich-Loeffler-Institut. L.M.Z. was supported by the Federal Excellence Initiative of Mecklenburg-Western Pomerania and European Social Fund (ESF) Grant KoInfekt (ESF/14-BM-A55-0002/16).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Light Sheet Microscopy-Assisted 3D Analysis of SARS-CoV-2 Infection in the Respiratory Tract of the Ferret ModelFinal published version, 6.01 MBLicence: CC BY

Cite this

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title = "Light sheet microscopy-assisted 3d analysis of sars-cov-2 infection in the respiratory tract of the ferret model",

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 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.",

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note = "Funding Information: The study was supported by intramural funding of the German Federal Ministry of Food and Agriculture provided to the Friedrich-Loeffler-Institut. L.M.Z. was supported by the Federal Excellence Initiative of Mecklenburg-Western Pomerania and European Social Fund (ESF) Grant KoInfekt (ESF/14-BM-A55-0002/16). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/v13030529",

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AU - Zaeck, Luca M.

AU - Scheibner, David

AU - Sehl, Julia

AU - Müller, Martin

AU - Hoffmann, Donata

AU - Beer, Martin

AU - Abdelwhab, Elsayed M.

AU - Mettenleiter, Thomas C.

AU - Breithaupt, Angele

AU - Finke, Stefan

N1 - Funding Information: The study was supported by intramural funding of the German Federal Ministry of Food and Agriculture provided to the Friedrich-Loeffler-Institut. L.M.Z. was supported by the Federal Excellence Initiative of Mecklenburg-Western Pomerania and European Social Fund (ESF) Grant KoInfekt (ESF/14-BM-A55-0002/16). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

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Light sheet microscopy-assisted 3d analysis of sars-cov-2 infection in the respiratory tract of the ferret model

Abstract

Bibliographical note

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