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

Wilco Nijenhuis, Hugo G.J. Damstra, Emma J. van Grinsven, Malina K. Iwanski, Patrique Praest, Zahra E. Soltani, Mariëlle M.P. van Grinsven, Jesse E. Brunsveld, Theun de Kort, Lisa W. Rodenburg, Dorien C.M. de Jong, Henriette H.M. Raeven, Sacha Spelier, Gimano D. Amatngalim, View ORCID ProfileAnna Akhmanova, Monique Nijhuis, Robert Jan Lebbink, Jeffrey M. Beekman, Lukas C. Kapitein
doi: https://doi.org/10.1101/2021.08.05.455126
Wilco Nijenhuis
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
5Centre for Living Technologies, Eindhoven-Wageningen-Utrecht Alliance, The Netherlands
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Hugo G.J. Damstra
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
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Emma J. van Grinsven
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
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Malina K. Iwanski
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
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Patrique Praest
4Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
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Zahra E. Soltani
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
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Mariëlle M.P. van Grinsven
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
4Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
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Jesse E. Brunsveld
2Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands
3Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
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Theun de Kort
4Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
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Lisa W. Rodenburg
2Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands
3Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
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Dorien C.M. de Jong
4Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
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Henriette H.M. Raeven
2Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands
3Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
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Sacha Spelier
2Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands
3Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
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Gimano D. Amatngalim
2Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands
3Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
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Anna Akhmanova
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
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  • ORCID record for Anna Akhmanova
Monique Nijhuis
4Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
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Robert Jan Lebbink
4Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
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Jeffrey M. Beekman
2Department of Pediatric Pulmonology, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands
3Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
5Centre for Living Technologies, Eindhoven-Wageningen-Utrecht Alliance, The Netherlands
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Lukas C. Kapitein
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
5Centre for Living Technologies, Eindhoven-Wageningen-Utrecht Alliance, The Netherlands
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  • For correspondence: l.kapitein@uu.nl
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Abstract

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.

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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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Optical nanoscopy reveals SARS-CoV-2-induced remodeling of human airway cells
Wilco Nijenhuis, Hugo G.J. Damstra, Emma J. van Grinsven, Malina K. Iwanski, Patrique Praest, Zahra E. Soltani, Mariëlle M.P. van Grinsven, Jesse E. Brunsveld, Theun de Kort, Lisa W. Rodenburg, Dorien C.M. de Jong, Henriette H.M. Raeven, Sacha Spelier, Gimano D. Amatngalim, Anna Akhmanova, Monique Nijhuis, Robert Jan Lebbink, Jeffrey M. Beekman, Lukas C. Kapitein
bioRxiv 2021.08.05.455126; doi: https://doi.org/10.1101/2021.08.05.455126
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Optical nanoscopy reveals SARS-CoV-2-induced remodeling of human airway cells
Wilco Nijenhuis, Hugo G.J. Damstra, Emma J. van Grinsven, Malina K. Iwanski, Patrique Praest, Zahra E. Soltani, Mariëlle M.P. van Grinsven, Jesse E. Brunsveld, Theun de Kort, Lisa W. Rodenburg, Dorien C.M. de Jong, Henriette H.M. Raeven, Sacha Spelier, Gimano D. Amatngalim, Anna Akhmanova, Monique Nijhuis, Robert Jan Lebbink, Jeffrey M. Beekman, Lukas C. Kapitein
bioRxiv 2021.08.05.455126; doi: https://doi.org/10.1101/2021.08.05.455126

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