PXD076103-1

PXD076103 is an original dataset announced via ProteomeXchange.

Title	Functional diversity of natural human IFNB1 variants in innate immunity
Description	Human interferon-beta (IFNβ), a type I IFN, is critical for effective innate immunity and is also an approved disease-modifying therapeutic. While genetic variations in several components of the type I IFN system are associated with infectious and immune diseases, consequences of IFNB1 variation remain unexplored. Here, we functionally evaluated 70 naturally-occurring rare protein-altering IFNB1 variants detected in humans globally. Twenty-five percent of all protein variants were found to be substantially less active than the common reference IFNβ, a phenotype that for many correlated with impaired ER-to-Golgi trafficking and poor secretion, or to weakened interaction with IFNAR1/IFNAR2 cell surface receptors. Strikingly, 3 IFNB1 variants, including one found to be homozygous in a single individual, encode for IFNβ proteins with enhanced capacity to engage IFNAR1/IFNAR2, and which exhibit greater signaling and antiviral potency than common IFNβ. As part of this project, we used mass spectrometry to compare the total proteome of A549 cells after stimulation with the hyperactive mutant IFNβ-ΔS13 and with wild type IFN (IFNβ-WT). We normalised IFN levels and tested both high and low doses. The hyperactive mutant induced interferon stimulated genes at levels similar to a ten-fold higher dose of IFNβ-WT.
HostingRepository	PRIDE
AnnounceDate	2026-08-13
AnnouncementXML	Submission_2026-08-13_04:06:28.220.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Jones
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-24 17:11:42	ID requested
⏵ 1	2026-08-13 04:06:28	announced

Dataset with its publication pending

submitter keyword: innate immunity, proteomics,Interferon, interferon stimulated genes

Benjamin G. Hale
contact affiliation	Institute for Medical Virology, University of Zurich
contact email	hale.ben@virology.uzh.ch
lab head
David Jones
contact affiliation	University of Zurich
contact email	david.jones@virology.uzh.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD076103
     1. Label: PRIDE project
     2. Name: Functional diversity of natural human IFNB1 variants in innate immunity