Optical nanoscopy reveals SARS-CoV-2-induced remodeling of human airway cells

A better understanding of host cell remodeling by the coronavirus SARS-CoV-2 is urgently needed to understand viral pathogenesis and guide drug development. Expression profiling and electron microscopy have frequently been used to study virus-host interactions, but these techniques do not readily en...

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Published inbioRxiv
Main Authors Nijenhuis, Wilco, Damstra, Hugo Gj, Van Grinsven, Emma J, Iwanski, Malina K, Praest, Patrique, Soltani, Zahra E, Marielle Mp Van Grinsven, Brunsveld, Jesse E, De Kort, Theun M, Rodenburg, Lisa W, Dorien Cm De Jong, Raeven, Henriette M, Spelier, Sacha, Amatngalim, Gimano D, Akhmanova, Anna, Nijhuis, Monique, Lebbink, Robert Jan, Beekman, Jeffrey M, Kapitein, Lukas Cm
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 05.08.2021
Subjects
Cell culture
Cilia
Coronaviruses
Drug development
Electron microscopy
Fluorescence microscopy
Golgi cells
Life cycles
Microscopy
Respiratory tract
Severe acute respiratory syndrome coronavirus 2
Ultrastructure
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Summary:A better understanding of host cell remodeling by the coronavirus SARS-CoV-2 is urgently needed to understand viral pathogenesis and guide drug development. Expression profiling and electron microscopy have frequently been used to study virus-host interactions, but these techniques do not readily enable spatial, sub-cellular and molecular analysis of specific cellular compartments. Here, we use diffraction-unlimited fluorescence microscopy to analyze how SARS-CoV-2 infection exploits and repurposes the subcellular architecture of primary human airway cells. Using STED nanoscopy, we detect viral entry factors along the motile cilia of ciliated cells and visualize key aspects of the viral life cycle. Using Tenfold Robust Expansion (TREx) microscopy, we analyze the extensively remodeled three-dimensional ultrastructure of SARS-CoV-2-infected ciliated cells and uncover Golgi fragmentation, emergence of large and atypical multivesicular bodies enclosing viral proteins, ciliary clustering, and remodeling of the apical surface. These results demonstrate a broadly applicable strategy to study how viruses reorganize host cells with spatial and molecular specificity and provide new insights into SARS-CoV-2 infection in primary human cell models. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.08.05.455126