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PreprintCited by 54Cytomegalovirus and herpesvirus researchAdvanced Proteomics Techniques and ApplicationsHerpesvirus Infections and Treatments

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Spatial, Quantitative and Functional Deconstruction of Virus and Host Protein Interactions Inside Intact Cytomegalovirus Particles

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Bogdanow, Boris, Gruska, Iris, Mühlberg, Lars, Protze, Jonas, Hohensee, Svea, Vetter, Barbara, Lehmann, Martin, Wiebusch, Lüder, Liu, Fan·2022·Nature Microbiology
DOI 10.1101/2022.05.02.490278PMC PMC10465357

Preprint — published as 10.1038/s41564-023-01433-8

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Abstract

Herpesviruses assemble large enveloped particles that are difficult to characterize structurally due to their size, fragility and complex proteome with partially amorphous nature. Here we use cross-linking mass spectrometry and quantitative proteomics to derive a spatially resolved interactome map of intact human cytomegalovirus virions. This enabled the de novo allocation of 32 viral proteins into four spatially resolved virion layers, each organized by a dominant viral scaffold protein. The viral protein UL32 engages with all layers in an N-to-C-terminal radial orientation bridging nucleocapsid to viral membrane. In addition, we observed the layer-specific recruitment of 82 host proteins, a subset of which are constitutively and selectively incorporated via specific host-virus interactions. We uncover how the recruitment of PP1 phosphatase and 14-3-3 proteins by UL32 affects early and late steps during viral biogenesis. Collectively, this study provides global structural insights into the native configuration of virus and host protein interactions inside herpesvirus particles.

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Metadata

Authors
Bogdanow, B., Gruska, I., Mühlberg, L., Protze, J., Hohensee, S., Vetter, B., Lehmann, M., Wiebusch, L., & Liu, F.
Affiliations
  • Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
  • Charité – Universitätsmedizin Berlin (DE)
  • Stiftung Charité (DE)
Corresponding author
  • Bogdanow, Boris
  • Wiebusch, Lüder
  • Liu, Fan
ORCID
Venue
Nature Microbiology
Publisher
openRxiv
Published
2022-05-02
Volume
8
Issue
9
Pages
1732-1747
ISSN
2058-5276 (ISSN-L)
DOI
10.1101/2022.05.02.490278
PMC
PMC10465357
OpenAlex
W4385638394
Cited by
54
References
2
Citations by year
2026: 13 · 2025: 15 · 2024: 21 · 2023: 4 · 2022: 1
FWCI
10.58
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Microbiology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Desy publication database (The Deutsches Elektronen-Synchrotron) (submittedVersion, cc-by)
  • DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron)
Funders
  • Princeton University
  • Helsingin Yliopisto
  • Wellcome Trust (209250/Z/17/Z), Z/17/Z)
  • Deutsche Forschungsgemeinschaft (BO5917/1-1, SFB1114/C03, SFB 958 / A04, 390874280, EXC2155, SFB 958, SFB1114)
  • Medizinischen Hochschule Hannover
  • Leibniz-Gemeinschaft (Leibniz-Wettbewerb P70/2018, P70/2018)
Topics
  • Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
Keywords
human cytomegalovirus, virus structure, host-virus interaction, 14-3-3 proteins, PP1 phosphatase, nucleocapsid, viral envelope, coarse-grained models
MeSH terms
Cytomegalovirus, Humans, Viral Proteins, Virion, Nucleocapsid, Proteome

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