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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
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Structural host-virus interactome profiling of intact infected cells.
Boris Bogdanow1,2, Lars Mühlberg3,4, Iris Gruska5
1Research group "Structural Interactomics", Leibniz Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany. boris.bogdanow@charite.de.
Nature Communications
|July 21, 2025
Summary
This study introduces a new method to map virus-host protein-protein interactions (PPIs) in infected cells. It reveals hundreds of previously unknown interactions critical for understanding viral infections.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Virus-host protein-protein interactions (PPIs) are crucial for viral pathogenesis.
- Identifying these interactions in their native cellular context at high resolution remains challenging.
Purpose of the Study:
- To develop and apply a novel method for high-resolution mapping of the virus-host structural interactome in intact infected cells.
- To gain detailed insights into the molecular determinants of herpes simplex virus 1 (HSV-1) interactions with human cells.
Main Methods:
- Combined in-cell cross-linking mass spectrometry with selective enrichment of newly synthesized viral proteins.
- Applied structural host-virus interactome profiling (SHVIP) to productively infected human cells.
- Integrated SHVIP data with AlphaFold-based structural modeling.
Main Results:
- Identified 739 virus-host PPIs based on 6,194 cross-links within infected cells.
- Mapped interactions across intracellular compartments and the host endomembrane system.
- Resolved PPIs to the protein domain level and predicted interaction sites in structured and disordered regions.
- Captured virus-host interactions missed by traditional proteomics.
Conclusions:
- SHVIP provides unprecedented insights into the structural interactome of HSV-1 infected cells.
- The method successfully identifies genuine virus-host PPIs in their native cellular environment.
- SHVIP data enhances structural modeling and aids in understanding viral infection mechanisms.
