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Lipid Droplet Biogenesis by Phase-Separated pORF3 Facilitates HEV Infectivity

GSE299317 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/06/09 Platform GPL20795
Summary
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.
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Also filed as BioProject PRJNA1273901 and SRA study SRP590815. Searching any of these in the dataset finder brings you back here.

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