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Egress of human cytomegalovirus through multivesicular bodies

View ORCID ProfileFelix J. Flomm, Timothy K. Soh, Carola Schneider, View ORCID ProfileHannah M. Britt, View ORCID ProfileKonstantinos Thalassinos, View ORCID ProfileSøren Pfitzner, Rudolph Reimer, View ORCID ProfileKay Grünewald, View ORCID ProfileJens B. Bosse
doi: https://doi.org/10.1101/2020.12.31.424954
Felix J. Flomm
1Centre for Structural Systems Biology, Hamburg, Germany
2Hannover Medical School, Institute of Virology, Hannover, Germany
3Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
4Leibniz-Institute for Experimental Virology (HPI), Hamburg, Germany
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Timothy K. Soh
1Centre for Structural Systems Biology, Hamburg, Germany
2Hannover Medical School, Institute of Virology, Hannover, Germany
3Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
4Leibniz-Institute for Experimental Virology (HPI), Hamburg, Germany
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Carola Schneider
4Leibniz-Institute for Experimental Virology (HPI), Hamburg, Germany
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Hannah M. Britt
5Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom
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Konstantinos Thalassinos
5Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom
6Institute of Structural and Molecular Biology, Birkbeck College, University of London, London, United Kingdom
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Søren Pfitzner
4Leibniz-Institute for Experimental Virology (HPI), Hamburg, Germany
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Rudolph Reimer
4Leibniz-Institute for Experimental Virology (HPI), Hamburg, Germany
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Kay Grünewald
1Centre for Structural Systems Biology, Hamburg, Germany
3Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
4Leibniz-Institute for Experimental Virology (HPI), Hamburg, Germany
7University of Hamburg, Department of Chemistry, Hamburg, Germany
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Jens B. Bosse
1Centre for Structural Systems Biology, Hamburg, Germany
2Hannover Medical School, Institute of Virology, Hannover, Germany
3Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
4Leibniz-Institute for Experimental Virology (HPI), Hamburg, Germany
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Abstract

Human Cytomegalovirus (HCMV) can infect a variety of cell types by using virions of varying glycoprotein composition. It is unclear how this diversity is generated, but spatiotemporally separated envelopment and egress pathways might play a role. So far, one egress pathway has been described in which HCMV particles are separately enveloped into individual vesicles and continuously exocytosed. However, some studies have also found enveloped virus particles inside multivesicular bodies (MVBs) but could not link them to productive egress or degradation pathways. We used a novel 3D-CLEM workflow to investigate MVBs in HCMV morphogenesis and egress. We found that HCMV envelopment occurred at MVBs and that virus-filled MVBs traversed the cytoplasm to release virions in bulk at the plasma membrane to form extracellular virus accumulations. Our data support the existence of a novel bona fide HCMV egress pathway, which opens the gate to evaluate divergent egress pathways in generating virion diversity.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Jens B. Bosse, Center for Structural Systems Biology, Notkestraße 85, 22607 Hamburg Email: jens.bernhard.bosse{at}cssb-hamburg.de

  • For this version of the manuscript we added additional experiments in figure 1 to show the prevalence of the phenotype investigated in this study. Further, to make the assesment of our EM data easier, we added the supplementary figures 1, 2 and 3. All figures have been updated and rearranged to best suit a digital format. A model has been added in figure 6 for clarity. All text sections have been updated to clarify the findings of the study and the biological implications.

Copyright 
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 4.0 International license.
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Posted June 24, 2021.
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Egress of human cytomegalovirus through multivesicular bodies
Felix J. Flomm, Timothy K. Soh, Carola Schneider, Hannah M. Britt, Konstantinos Thalassinos, Søren Pfitzner, Rudolph Reimer, Kay Grünewald, Jens B. Bosse
bioRxiv 2020.12.31.424954; doi: https://doi.org/10.1101/2020.12.31.424954
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Egress of human cytomegalovirus through multivesicular bodies
Felix J. Flomm, Timothy K. Soh, Carola Schneider, Hannah M. Britt, Konstantinos Thalassinos, Søren Pfitzner, Rudolph Reimer, Kay Grünewald, Jens B. Bosse
bioRxiv 2020.12.31.424954; doi: https://doi.org/10.1101/2020.12.31.424954

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