PXD079488

PXD079488 is an original dataset announced via ProteomeXchange.

Title	From Infection to Insulin Failure: How SARS-CoV-2 Triggers beta cell disruption through IAPP Aggregation
Description	Global diabetes incidence has surged post-COVID-19, yet how SARS-CoV-2 drives long-term beta cell (β-cell) failure remains incompletely elucidated. We identify a mechanism whereby SARS-CoV-2 structural proteins directly hijack islet amyloid polypeptide (IAPP) to induce pathogenic amyloid deposition, disrupting insulin granule maturation, trafficking, and secretion in an age-susceptible islet microenvironment. In macaque models, aged subjects showed extensive islet IAPP aggregation with increased β-cell necroptosis, whereas adult infected animals exhibited minimal IAPP pathology. Multiplex fluorescence in situ hybridization detecting viral sense and antisense RNAs with IAPP immunostaining revealed focal overlap of active viral replication foci with IAPP-rich amyloid regions in aged islets. Molecular docking was used as a hypothesis-generating tool, whereas co-immunoprecipitation, proximity ligation assays, and surface plasmon resonance experimentally confirmed direct Spike/Nucleocapsid-IAPP binding; interface-guided peptide mutagenesis further showed that five predicted IAPP contact residues are required for binding. Thioflavin-T kinetics and electron microscopy demonstrated that Spike/Nucleocapsid markedly accelerated IAPP monomer conversion into dense fibrillar networks. In β cells and primary hIAPP-overexpressing mouse islets, Spike/Nucleocapsid expression or protein exposure reduced insulin content and induced endoplasmic reticulum stress and inflammatory programs. Integrated spatial islet proteomics linked IAPP-viral complexes to complement activation and vesicle-transport dysfunction. Crucially, primary-islet qPCR and immunoblotting revealed stalled insulin mRNA with compensatory upregulation of trafficking/exocytosis transcripts but accumulation of insulin precursor proteins, consistent with impaired granule maturation/processing. Thus, SARS-CoV-2 proteins act as pathogenic “seeds” for IAPP assembly, establishing an IAPP aggregation-impaired granule maturation-complement activation-vesicle transport blockade axis underlying age-associated vulnerability to post-COVID-19 diabetes.
HostingRepository	iProX
AnnounceDate	2026-06-09
AnnouncementXML	Submission_2026-06-09_18:50:39.399.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhiqi Song
SpeciesList	scientific name: Macaca mulatta; NCBI TaxID: 9544;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-06-09 18:50:24	ID requested
⏵ 1	2026-06-09 18:50:39	announced

Dataset with its publication pending

submitter keyword: islet amyloid polypeptide, β-cell, Insulin Failure, SARS-CoV-2, post-COVID-19 diabetes

Wei Deng
contact affiliation	Chinese Academy of Medical Sciences and Comparative Medicine Center
contact email	dengwei717@163.com
lab head
Zhiqi Song
contact affiliation	Chinese Academy of Medical Sciences and Comparative Medicine Center
contact email	songzhiqi1989@foxmail.com
dataset submitter

iProX dataset URI