The Very Virulent IBDV Viral Protein VP3 Promotes the Caspase-3 Mediated Cleavage of GSDME

The infectious bursal disease virus (IBDV) can cause severe immunosuppression and high mortality in chickens, posing a significant threat to the poultry farming industry. Pyroptosis mediated by gasdermin E (GSDME) may be closely related to the tissue damage caused by IBDV. In this study, 3-week-old specific-pathogen-free (SPF) White Leghorns chickens were inoculated intranasally with 1000 copies/200 μL of very virulent IBDV (vvIBDV) Gx strain, and we analyzed GSDME expression in chicken tissues and the cleavage site of GSDME by Caspase-3. Tissue distribution results showed that GSDME and IL-1β transcription in the bursa of Fabricius and kidneys were significantly upregulated by more than five-fold (p < 0.01) following vvIBDV infection, indicating a close association with vvIBDV-induced tissue lesions. Further studies demonstrated that Caspase-3 could cleave GSDME at conserved sites (D270), releasing the active N-terminal fragment (GSDME-N) to induce pyroptosis. Furthermore, although IBDV proteins cannot directly cleave GSDME, the viral protein VP3 enhances Caspase-3-mediated GSDME cleavage, thereby triggering pyroptosis. The above results reveal the role of GSDME-dependent pyroptosis in the pathogenesis of IBDV and provide new ideas for the prevention and control strategies against IBDV.