PXD055348-1

PXD055348 is an original dataset announced via ProteomeXchange.

Title	A HEV ORF2 protein-mediated mechanism of hepatitis E-associated kidney disease
Description	Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN developed in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a mechanistic explanation of how the actually hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications.
HostingRepository	PRIDE
AnnounceDate	2025-01-18
AnnouncementXML	Submission_2025-01-17_20:03:20.916.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anne-Laure Leblond
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-29 04:50:33	ID requested
⏵ 1	2025-01-17 20:03:21	announced

10.1038/s41467-024-53072-0;

Leblond AL, Helmchen B, Ankavay M, Lenggenhager D, Jetzer J, Helmchen F, Yurtsever H, Parrotta R, Healy ME, P, ö, schel A, Markkanen E, Semmo N, Ferri, é M, Cocquerel L, Seeger H, Hopfer H, M, ü, llhaupt B, Gouttenoire J, Moradpour D, Gaspert A, Weber A, complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status. Nat Commun, 15(1):8849(2024) [pubmed]

submitter keyword: infected or not with hepatitis E virus. Laser-captured samples, LC-MSMS,Human liver and kidney samples

Prof. Dr.
contact affiliation	Department of Pathology and Molecular Pathology, University of Zurich (UZH) and University Hospital Zurich (USZ), Zurich, Switzerland.
contact email	achim.weber@usz.ch
lab head
Anne-Laure Leblond
contact affiliation	Department of pathology and molecular pathology
contact email	anne-laure.leblond@usz.ch
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/01/PXD055348

PRIDE project URI

• PRIDE
  1. PXD055348
     1. Label: PRIDE project
     2. Name: A HEV ORF2 protein-mediated mechanism of hepatitis E-associated kidney disease