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Structural Host Virus Interactome Profiling of Intact Infected Cells

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 crosslinking mass spectrometry with the enrichment of newly synthesized viral proteins from 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.

INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Fusion, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human) Human Alphaherpesvirus 1

TISSUE(S): Lung, Fibroblast

SUBMITTER: Boris Bogdanow

LAB HEAD: Fan Liu

PROVIDER: PXD047422 | Pride | 2025-06-13

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	APMS_HA_UL12_MAPK8mut_txt.7z	Other
	APMS_HA_UL47_DDB1mut_txt.7z	Other
	APMS_HA_UL49_PP1mut_txt.7z	Other
	E1_20200131_BB_BB9_HSVEN1.raw	Raw
	E1_20200131_BB_BB9_HSVEN2.raw	Raw

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Structural Host Virus Interactome Profiling of Intact Infected Cells

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