PXD071226-1

PXD071226 is an original dataset announced via ProteomeXchange.

Title	Snapshot of in-cell protein contact sites reveals new host factors and hijacking of paraspeckles during influenza A virus infection
Description	Influenza A virus (IAV) hijacks host cellular machinery, but many virus–IAV interactions and contacting protein sites remain uncharacterised, particularly those dependent on intact cellular architecture, such as membrane-associated or phase- separated compartments. Here, we applied in-cell cross-linking mass spectrometry (XL-MS), integrated with AlphaFold-based structural modelling and functional assays, to map protein-protein contact sites in IAV-infected human cells. This approach revealed previously unrecognised virus–host interactions linked to spatially organised processes, including the maturation pathway of HA through the membrane-bound ER– Golgi system, the novel interaction of M2 with the membrane-embedded LAT1 amino acid transporter, and the progressive disassembly of paraspeckles–phase-separated compartments in the nucleus. We validate M2-LAT1 interaction and paraspeckle disassembly in human primary lung epithelial cells and show that the paraspeckle disassembly constitutes a new and unique infection mechanism through which IAV releases RNA-binding proteins that support viral RNA replication. These findings advance the understanding of IAV manipulation of host cellular processes and illustrate how the integrative in-cell structural system biology approach captures native host-pathogen interactomes, infection pathways, and host cell perturbations.
HostingRepository	PRIDE
AnnounceDate	2026-04-24
AnnouncementXML	Submission_2026-04-24_07:47:06.206.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lars Mühlberg
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Influenza A virus (A/WSN/1933(H1N1)); NCBI TaxID: NEWT:382835;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-25 16:29:10	ID requested
⏵ 1	2026-04-24 07:47:06	announced

Dataset with its publication pending

submitter keyword: bioorthogonal labeling,Influenza A virus, cross-linking mass spectrometry, affinity purification mass spectrometry

Fan Liu
contact affiliation	Department of Structural Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany
contact email	FLiu@fmp-berlin.de
lab head
Lars Mühlberg
contact affiliation	Leibniz-Forschungsinstitut für Molekulare Pharmakologie
contact email	muehlberg@fmp-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD071226
     1. Label: PRIDE project
     2. Name: Snapshot of in-cell protein contact sites reveals new host factors and hijacking of paraspeckles during influenza A virus infection