Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lipid Droplet Biogenesis by Phase-Separated pORF3 Facilitates HEV Infectivity

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE299317 | GEO | 2025/06/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Lipid Droplet Biogenesis by Phase-Separated pORF3 Facilitates HEV Infectivity

Project description:Lipid Droplet Biogenesis by Phase-Separated pORF3 Facilitates HEV Infectivity

| PRJNA1273901 | ENA

Quantitative Lipid Droplet Proteome Analysis Identifies Annexin A3 as a Cofactor for HCV Particle Production

Project description:Cytosolic lipid droplets (LDs) are vital to Hepatitis C Virus (HCV) infection as the putative sites of virion assembly. To identify novel regulators of HCV particle production, we performed quantitative LD proteome analysis. Huh7.5 cells were labeled by stable isotope labeling with heavy amino acids in cell culture (SILAC) and subsequently infected with an HCV Jc1 reporter virus. After selection for HCV-infected cells, equal amounts of HCV-infected and uninfected control cells were mixed, LDs were isolated and analyzed by LC-ESI-MS/MS.

2016-09-26 | PXD004707 | Pride

Comparative analysis of gene expression upon DMSO-induced differentiation of hepatoma cell lines [Dif]

Project description:The liver, and more precisely hepatocytes, can be infected by several viruses such as hepatitis B (HBV), hepatitis D (HDV), hepatitis C (HCV), hepatitis E (HEV) viruses, with chronic infection leading to end-stage liver diseases. Since no in vitro model allowing multi-infections with the four viruses is reported, limited data are available on the interplay between those viruses as well as on the potential cross-reactivity of antivirals in multi-infection cases. Here we showed that HuH7.5-NTCP cells can be partially differentiated into hepatocyte-like cells and genuinely replicate HBV, HDV, HCV and HEV for at least 4 weeks after mono or multiple infections. Additionally, we recapitulated the effect of known antivirals and found that FXR-agonists, also strongly inhibited HEV replication. Using HEV infected HuHep mice, we confirmed the antiviral effect of Vonafexor, the FXR agonist clinical candidate currently tested against HBV and HDV, highlighting FXR-ligands as potential broad acting antivirals. Here, we set-up the first in vitro model allowing multi-infections with hepatitis viruses that can be used for broad drug screening.

2025-04-23 | GSE288204 | GEO

Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation

Project description:Neural stem/progenitor cells (NSPCs) generate new neurons throughout adulthood. However, the underlying regulatory processes are still not fully understood. Lipid metabolism plays an important role in regulating NSPC activity: build-up of lipids is crucial for NSPC proliferation, whereas break-down of lipids has been shown to regulate NSPC quiescence. Despite their central role for cellular lipid metabolism, the role of lipid droplets (LDs), the lipid storing organelles, in NSPCs remains underexplored. Here we show that LDs are highly abundant in adult mouse NSPCs, and that LD accumulation is significantly altered upon fate changes such as quiescence and differentiation. NSPC proliferation is influenced by the number of LDs, inhibition of LD build-up, breakdown or usage, and the asymmetric inheritance of LDs during mitosis. Furthermore, high LD-containing NSPCs have increased metabolic activity and capacity, but do not suffer from increased oxidative damage. Together, these data indicate an instructive role for LDs in driving NSPC behaviour.

2021-11-10 | GSE187470 | GEO

LIPID DROPLET PROTEIN OF SEEDS (LDPS) influences lipid droplet size and number in seeds and seedlings

Project description:Lipid droplets (LDs) are subcellular organelles found in all kingdoms of life. While LDs are well known as intracellular depots for neutral lipid storage, there is a growing appreciation that they are much more dynamic in terms of their functions. For instance, recent work in yeast and mammalian systems have revealed that LDs are involved in stress response, protein sequestration, and development, and that these roles are mediated by distinct proteins located on the LD surface. However, few yeast and mammalian LD proteins have obvious homologs in plants. Indeed, relatively few plant LD proteins have been characterized, limiting our overall understanding of the molecular mechanisms underlying LD biogenesis, maintenance, and turnover in plant cells. To address this, we have performed proteomic surveys of LDs isolated from various Arabidopsis tissues, and here we discuss the characterization of one such newly identified LD protein, LIPID DROPLET PROTEIN OF SEEDS (LDPS). LDPS in Arabidopsis is annotated to be of unknown function and is expressed exclusively in developing and mature seeds, as well as in young seedlings. Notably, mature ldps mutant seeds have smaller LDs and less storage oil relative to wild-type seeds, while ectopic overexpression of LDPS in leaves leads to an increase in LD number. Furthermore, following germination, LDs in ldps mutant seedlings do not appear to fuse during their turnover, as they do in wild-type seedlings. Protein-protein interaction assays combined with protein co-expression experiments suggest that LDPS interacts with other known LD proteins, in particular, oleosins. Taken together, these findings and those from proteomics and lipidomics analyses of ldps mutant seeds indicate that LDPS plays a key role in LD biogenesis and regulating LD size and number in plant seeds.

2025-06-09 | PXD041506 | Pride

Proteomic characterization of LDIP mutant phenotypes in Arabidopsis seedlings

Project description:Lipid droplets (LDs) are unique, protein-coated organelles found in all eukaryotic organisms that function primarily in the storage of energy-rich neutral lipids, such as triacylglycerols (TAGs). In plants, LDs are found in high abundance in oilseeds, and proteins involved in their formation and activity, such as oleosins, have been well-characterized. Our understanding of LD biogenesis and activity in other cell types, as well as the proteins that regulate these processes, is not as comprehensive. We recently identified and characterized a novel Arabidopsis LD coat protein termed LDIP (LDAP-interacting protein) that regulates LD size and neutral lipid homeostasis in leaf and seed embryonic cells. Here, we show that LDIP plays a distinct role in regulating LD size during biogenesis in leaf cells via interactions with key biogenetic proteins. Localization experiments performed in both plant and insect cells revealed LDIP is necessarily recruited to the LD surface by LDAP3 and binds nascent LDs during early-stage LD formation. Pull-down and Y2H assays indicate LDIP interacts with the biogenetic proteins SEIPINs, while combinatory expression levels of these proteins resulted in aberrant LD size and number in both plant cells and yeast. Evidence is also provided that LDIP plays a key role in modulating phospholipid levels in both leaves and seeds. Taken together, our data allow for the generation of model for LD biogenesis in non-seed cell types.

2022-02-15 | PXD012992 | Pride

Arabidopsis LDIP is an LDAP-interacting protein that influences lipid droplet biogenesis and neutral lipid homeostasis in both leaves and seeds

Project description:Cytoplasmic lipid droplets (LDs) are found in all types of plant cells where they are derived from the endoplasmic reticulum (ER) and function as a repository for neutral lipids, as well as serving in lipid remodelling and signalling. However, the mechanisms underlying the formation and functioning of plant LDs, particularly in non-seed tissues, are relatively unknown. Previously, we showed that the LD-Associated Proteins (LDAPs) are a family of plant-specific, LD surface-associated coat proteins that are required for proper LD biogenesis and neutral lipid homeostasis in vegetative tissues. Here, we screened a yeast two-hybrid library using Arabidopsis LDAP3 as ‘bait’ in an effort to identify other novel LD protein constituents. One of the candidate LDAP3-interacting proteins was Arabidopsis At5g16550, which is a plant-specific protein of unknown function that we termed LDIP (LDAP-interacting protein). Using a combination of biochemical and cellular approaches, we show that LDIP targets specifically to the LD surface, contains a discrete amphipathic -helical targeting sequence, and participates in both homotypic and heterotypic associations with itself and LDAP3, respectively. Analysis of LDIP T-DNA knockdown and knockout mutants showed a decrease in LD abundance and increase in variability of LD size in leaves, with concomitant increases in total neutral lipid content. Similar phenotypes were observed in plant seeds, which showed enlarged LDs and increases in total seed oil amounts. Collectively, these data identify LDIP as a new player in LD biogenesis in plants that modulates both LD size and cellular neutral lipid homeostasis. Potential mechanisms of LDIP activity are discussed.

2017-11-06 | PXD007192 | Pride

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

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

Systematic genome perturbation reveals coordination of lipid droplets and metabolic gene regulation

Project description:Lipid droplets (LDs) store lipids for metabolic energy and are central to cellular lipid homeostasis. The mechanisms coordinating lipid storage in LDs with cellular metabolism are unclear but relevant to obesity-related diseases. Here we utilized genome-wide screening to identify genes that modulate lipid storage in human macrophages, a cell type relevant to metabolic diseases. Among ~550 genes regulating lipid storage, we identify MLX, a basic helix-loop-helix leucine-zipper transcription factor that regulates multiple metabolic processes. We show that MLX and family members MLXIP/MondoA and MLXIPL/ChREBP bind LDs via C-terminal amphipathic helices. When LDs increase in cells, LD binding of MLX, MLXIP/MondoA, and MLXIPL/ChREBP reduces their transcriptional activity, whereas the absence of LDs results in hyperactivation. Our findings uncover an unexpected component to a lipid storage response, in which binding of MLX transcription factors to the LD surface modulates their activity, adjusting the expression of metabolic genes to lipid storage levels.

2020-01-01 | GSE126002 | GEO

The impact of genetic stress by ATGL deficiency on the lipidome of lipid droplets from murine hepatocytes

Project description:We showed earlier that nutritional stress like starvation or high fat diet resulted in phenotypic changes in the lipidomes of hepatocyte lipid droplets (LDs), representative for the pathophysiological status of the mouse model. Here we extend our former study by adding genetic stress due to knock-out (KO) of adipocyte triglyceride lipase (ATGL), the rate limiting enzyme in LD lipolysis. An intervention trial for 6 weeks with male wild-type (WT) and ATGL-KO mice was carried out; both genotypes were fed lab chow or were exposed to short-time starvation. Isolated LDs were analyzed by LC-MS/MS. Triacylglycerol, diacylglycerol and phosphatidylcholine lipidomes, in that order, provided best phenotypic signatures characteristic for respective stresses applied to the animals. This was evidenced at lipid species level by principal component analysis, calculation of average values for chain-lengths and numbers of double bonds, and by visualization in heat maps. Structural backgrounds for analyses and metabolic relationships were elaborated at lipid molecular species level. Relating our lipidomic data to non-alcoholic fatty liver diseases of nutritional and genetic etiologies with or without accompanying insulin resistance, phenotypic distinction in hepatocyte LDs dependent on insulin status emerged. Taken together, lipidomes of hepatocyte lipid droplets are sensitive responders to nutritional and genetic stress.

2014-08-19 | MTBLS81 | MetaboLights

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data