Gasdermin E couples viral pyroptosis to lethal hepatic lipid accumulation.

Gasdermin E-mediated pyroptosis drives lethal hepatic lipid accumulation in WELV-infected hosts, with GSDME knockout providing complete protection.

• Why it matters: Understanding how orthonairoviruses cause severe liver damage is crucial for developing effective treatments, as current knowledge of their pathogenesis is limited.
• What they did: The study used cellular and animal models to demonstrate that WELV infection activates GSDME-dependent pyroptosis via mitochondrial and Fas pathways, leading to lipid dysregulation, with GSDME interacting with FASN to promote steatosis.
• The result: Inhibiting caspases or FASN reduces liver damage and improves survival, positioning GSDME as a key target for antiviral therapy and revealing a pyroptosis-metabolism axis in virus-induced liver injury.