PT  - JOURNAL ARTICLE
AU  - Luca M. Zaeck
AU  - David Scheibner
AU  - Julia Sehl
AU  - Martin Müller
AU  - Donata Hoffmann
AU  - Martin Beer
AU  - Elsayed M. Abdelwhab
AU  - Thomas C. Mettenleiter
AU  - Angele Breithaupt
AU  - Stefan Finke
TI  - 3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract
AID  - 10.1101/2020.10.17.339051
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.17.339051
4099  - http://biorxiv.org/content/early/2020/10/18/2020.10.17.339051.short
4100  - http://biorxiv.org/content/early/2020/10/18/2020.10.17.339051.full
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 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 StatementThe authors have declared no competing interest.