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PreprintCited by 15Advanced Proteomics Techniques and ApplicationsHerpesvirus Infections and TreatmentsMass Spectrometry Techniques and Applications

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Structural Host-Virus Interactome Profiling of Intact Infected Cells

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Bogdanow, Boris, Mühlberg, Lars, Gruska, Iris, Vetter, Barbara, Ruta, Julia, Elofsson, Arne, Wiebusch, Lüder, Liu, Fan·2023·Nature Communications
DOI 10.1101/2023.12.03.569778PMC PMC12280212

Preprint — published as 10.1038/s41467-025-61618-z

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Abstract

Virus-host protein-protein interactions (PPIs) are fundamental to viral infections, yet high-resolution identification within the native context of intact infected cells has remained an unsolved challenge. Here, we developed structural host-virus interactome profiling (SHVIP) that combines in situ cross-linking mass spectrometry with the enrichment of newly synthesized viral proteins from infected cells. We established SHVIP using herpes simplex virus type 1 and obtained 739 PPIs based on 6,194 cross-links from productively infected cells. SHVIP captures PPIs across intracellular compartments and at the intact host endomembrane system. It resolves PPIs to the protein domain level and seamlessly integrates with AlphaFold-based structural modeling, facilitating detailed predictions of PPI sites within structured and intrinsically disordered regions. We show that SHVIP captures parts of the virus-host PPI space that are elusive to traditional interaction proteomics approaches. By selectively disrupting several newly identified virus-host PPIs, we confirm SHVIP’s ability to uncover genuine virus-host PPIs in the intact complex environment of infected cells.

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Metadata

Authors
Bogdanow, B., Mühlberg, L., Gruska, I., Vetter, B., Ruta, J., Elofsson, A., Wiebusch, L., & Liu, F.
Affiliations
  • Humboldt-Universität zu Berlin (DE)
  • Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
  • Charité – Universitätsmedizin Berlin (DE)
  • Stockholm University (SE)
  • Stiftung Charité (DE)
Corresponding author
  • Bogdanow, Boris
  • Wiebusch, Lüder
  • Liu, Fan
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2023-12-03
Volume
16
Issue
1
Pages
6713-6713
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2023.12.03.569778
PMC
PMC12280212
OpenAlex
W4412535389
Cited by
15
References
1
Citations by year
2026: 12 · 2025: 3
FWCI
3.78
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Swedish e-Science Research Centre
  • Deutsche Forschungsgemeinschaft (BO5917/1-1)
  • Knut och Alice Wallenbergs Stiftelse (Berzelius-2021-29.)
  • Vetenskapsrådet (2016-06301, Berzelius-2021-29)
  • Leibniz-Gemeinschaft (K284 /2019, P70/2018)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
Keywords
herpes simplex virus type 1, host-virus interactome, endomembrane system, intrinsically disordered regions, productive infection
MeSH terms
Humans, Mass Spectrometry, Viral Proteins, Herpesvirus 1, Human, Protein Interaction Mapping, Proteomics, Host-Pathogen Interactions, Protein Interaction Maps

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