A HEV ORF2 protein-mediated mechanism of hepatitis E-associated kidney disease

Author:

Helmchen Birgit,Leblond Anne-LaureORCID,Lenggenhager DanielaORCID,Jetzer Jasna,Ankavay MalikiORCID,Helmchen FritjofORCID,Yurtsever Hueseyin,Parrotta RossellaORCID,Healy Marc E.ORCID,Pöschel AmiskwiaORCID,Markkanen EnniORCID,Semmo NasserORCID,Ferrié Martin,Cocquerel LaurenceORCID,Seeger HaraldORCID,Hopfer HelmutORCID,Müllhaupt Beat,Gouttenoire Jérôme,Moradpour DariusORCID,Gaspert ArianaORCID,Weber AchimORCID

Abstract

AbstractHepatitis 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 ade novoimmune 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 noninfectious form of HEV open reading frame 2 (ORF2, capsid) protein secreted in excess. HEV particles or RNA, however, were not detectable. Patients with acute hepatitis E displayed similar but less pronounced deposits. Our results elucidate an immunologic mechanism by which this hepatotropic virus causes variable renal manifestations and establish a link between the HEV ORF2 protein and hepatitis E-associated GN. They directly provide a tool for etiology-based diagnosis of HEV-associated GN as a distinct entity and suggest therapeutic implications.

Publisher

Cold Spring Harbor Laboratory

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