Similar Datasets
Project description:What happens in cells infected with HEV is largely unknown. We used a recently established genotype 3 HEV cell culture system and profiled the host responses by RNA-seq.
2019-10-31 | GSE88731 | GEO
Project description:High endothelial venules (HEVs) play a crucial role in immunological responses by facilitating lymphocyte entry into the lymph node through display of peripheral node addressins (PNAd). During inflammation, the HEV network expands and upregulates additional adhesion molecules for proper T cell influx, but the underlying mechanisms remain poorly understood. Here we report that autophagy is essential for the proper expansion and functioning of HEVs using single-cell transcriptomics, intravital imaging, and novel inducible HEV tracer mouse models. We demonstrate that lack of autophagy leads to a loss of HEV phenotype and functionality through reduced lymphotoxin beta receptor and Unfolded Protein Response activation, which contribute to decreased production of PNAd. This autophagy-dependent mechanism maintains HEV identity during inflammatory stress. These findings reveal that blocking HEV expansion can be exploited therapeutically, as demonstrated in a psoriasis model where it resulted in less severe disease phenotype.
2026-08-10 | GSE300153 | GEO
Project description:Lipid droplets (LDs) are dynamic organelles mediating lipid metabolism and diverse cellular processes. However, the interplay between hepatocyte LDs and hepatitis E remains poorly understood. Using targeted lipidomics and lipid profiling, we reveal in cellular and rodent models that hepatitis E virus (HEV) infection substantially increases hepatocyte LD biogenesis. Mechanistically, HEV pORF3 is a key LD biogenesis inducer and an essential factor for viral infectivity in vivo. pORF3 formed a unique LD organelle through its liquid-liquid phase-separation (LLPS) property, associating with enhancing cholesterol anabolic pathways, thereby facilitating the synthesis of triglycerides and cholesterol esters. Accordingly, deleting ORF3 or inhibiting LD biogenesis with LD-lowering agent atorvastatin substantially suppressed HEV infection in vivo. These findings position LDs as critical hubs for HEV infection, reveal lipid biogenesis as a crucial function of HEV infectivity, and suggest alternative strategies for HEV intervention.
2025-06-09 | GSE299317 | GEO
Project description:Hepatitis E virus (HEV) is a globally prevalent pathogen that causes 20 million infections and 60,000 fatalities annually, endangering particularly pregnant women and immunosuppressed individuals. Liver cirrhosis, which results from advanced fibrosis, is the primary symptom and leading mortality cause in chronic hepatitis E patients. However, the causation and process of liver fibrosis triggered by chronic HEV infection remain poorly understood. Here, we unexpectedly discovered that the viral multiple-domain replicase (ORF1) undergoes unique ubiquitin-proteasomal processing in HEV replicon hepatocytes, HEV-infected gerbil livers, and HEV-infected patient livers, which follows a CHIP-mediated K48 ubiquitination and produces the HEV-Derived Smad Activator (HDSA). Lacking putative helicase and RNA polymerase domains, this enriched viral polypeptide in hepatocytes and gerbil livers is non-HSP90-bound, stable, and exhibits exclusively nuclear localization. Surprisingly, HDSA markedly potentiates the fibrogenic TGF-β/Smad pathway in livers by facilitating promoter binding and coactivator recruitment of SMAD3, leading to profound liver fibrotic symptoms and damage. Thus, we have identified the first viral protein derived from the unique proteasomal processing of the host, defined its notable role in liver fibrosis, and highlighted the nature of complex host-HEV interactions that drives HEV pathogenesis.
2024-08-01 | GSE251924 | GEO
Project description:Hepatitis E virus genotype 3 (HEV-3) is a zoonotic pathogen with pigs representing the natural host. Although HEV-3 infections in humans are often self-limiting, severe or chronic cases can occur. In contrast, HEV-3 infections in pigs, the primary reservoir, remain asymptomatic. To assess the initial transcriptional response in porcine cells during HEV-3 infection and pave the way for mechanistic studies of species-specific virus-host interactions, we aimed to establish porcine cell culture models, including primary porcine hepatocytes (PPHs) and porcine cell lines. PPHs supported the full HEV-3 replication cycle while intrinsic immunity, driven by the interferon-stimulated gene (ISG) system, played a central role in restricting viral replication. JAK-inhibition enhanced viral replication and suppressed ISG expression, highlighting the importance of IFN signaling in antiviral defense. Transcriptional profiling revealed a global modulation of host responses upon HEV infection, including pathways linked to immunity, inflammation, and metabolism. Porcine cell lines were permissive to HEV infection and treatment with recombinant porcine IFN-α subtypes induced a robust ISG response and effectively inhibited HEV replication in a dose-dependent manner. These findings establish porcine hepatocytes and cell lines as valuable tools to study HEV-host interactions, demonstrating the critical role of IFN-mediated intrinsic immunity in HEV restriction and highlighting subtype-specific antiviral effects of porcine IFN-α.
2026-07-01 | GSE295453 | GEO
Project description:Paslahepevirus balayani (HEV) sequencing
| PRJEB107200 | ENA
Project 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.
2025-01-18 | PXD055348 | Pride
Project description:HEV in transplant recipients in Switzerland
| PRJEB52483 | ENA
Project description:We aimed to identify interferon (IFN)-regulated genes that are differentially expressed during chronic HEV infection in human hepatocytes, the main site of HEV replication, using HepaRG cells.
2023-11-08 | GSE243860 | GEO
Project description:We aimed to identify interferon (IFN)-regulated genes that are differentially expressed during chronic HEV infection in human hepatocytes, the main site of HEV replication, using HepaRG cells.
2023-11-08 | GSE243856 | GEO