PXD074316

PXD074316 is an original dataset announced via ProteomeXchange.

Title	PRM analysis of protease activity
Description	Influenza A virus (IAV) is a zoonotic pathogen capable of infecting diverse avian and mammalian hosts, causing seasonal epidemics and occasional global pandemics in humans. Viral entry requires proteolytic activation of hemagglutinin (HA). While serine proteases such as TMPRSS2, and HAT are known HA activators, the respiratory tract harbours additional proteases whose contributions to infection remain unclear. Dysregulation of these proteases can enhance viral replication, tissue damage, and inflammation, highlighting the need for a systems-level view of the proteolytic landscape. Here, we use high-throughput, proteome-wide proteomics and N-terminomics to identify 112 host proteases across the nasal mucosa, trachea, and lung. We monitor and validate 28 proteases with targeted proteomics and microfluidic qPCR, representing a comprehensive degradome analysis in the respiratory tract of the highly translational pig model of influenza infection. We show that protease abundance and activity were highly tissue-specific: while the nasal mucosa showed selective activation of broad- and narrow-specificity proteases alongside robust antiviral responses, the trachea exhibited modest modulation with subtle shifts in protease–inhibitor balance, and the lung maintained predominantly active proteases despite lower viral loads but severe tissue damage, indicative of immune-mediated pathology. Sequence motif analysis revealed distinct cleavage preferences across tissues, indicating differential protease processing across the studied respiratory tissues in antiviral pathways, antigen processing, and tissue remodelling. Several identified proteases, including ST14, KLKB1, PRSS8, and LGMN, were increased and functionally active upon infection, suggesting roles in viral processing and host immune regulation. Collectively, our results define a spatially organised proteolytic network that shapes tissue-specific antiviral host responses and contributes to H1N1 influenza pathogenesis.
HostingRepository	PanoramaPublic
AnnounceDate	2026-03-05
AnnouncementXML	Submission_2026-03-05_19:35:34.707.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Chrysillis Hellemann Polhaus
SpeciesList	scientific name: Sus scrofa; NCBI TaxID: 9823;
ModificationList	Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-10 19:10:28	ID requested
⏵ 1	2026-03-05 19:35:35	announced

Dataset with its publication pending

submitter keyword: Influenza A virus, Innate Immunity, Proteolytic landscape

Konstantinos Kalogeropoulos
contact affiliation	Technical University of Denmark, Department of Biotechnology and Biomedicine and Center for Translational Protein Design, Kongens Lyngby, 2800, Denmark; Delft University of Technology, Department of Bionanoscience and Kavli Institute of Nanoscience, Delft, 2629 HZ, Netherlands.
contact email	uadk@dtu.dk
lab head
Chrysillis Hellemann Polhaus
contact affiliation	Technical University of Denmark, Department of Biotechnology and Biomedicine, Kongens Lyngby, 2800, Denmark
contact email	cjmp@dtu.dk
dataset submitter

Panorama Public dataset URI