Histone H3K27 acetylation mediated by KAT8 maintains antiviral trained immunity in shrimp induced by inactivated white spot syndrome virus

Shrimp aquaculture is critically important for global food security, but viral diseases like white spot syndrome virus (WSSV) cause devastating economic losses, highlighting the urgent need for effective disease control strategies. While trained immunity has been observed in invertebrates like shrimp after exposure to pathogens, the underlying molecular mechanisms remain elusive. Here we reveal that lysine acetyltransferase KAT8-mediated histone H3K27ac is critical for antiviral defense in shrimp Marsupenaeus japonicus. We demonstrate that ultraviolet-inactivated WSSV (UV-WSSV) induces antiviral trained immunity in the shrimp via KAT8-dependent H3K27ac. UV-WSSV training enhances glycolysis and the tricarboxylic acid (TCA) cycle, increasing acetyl-CoA production. This acetyl-CoA fuels KAT8 activity, depositing H3K27ac marks at the promoter of the NF-κB-like transcription factor Dorsal. This epigenetic modification upregulates Dorsal expression, leading to the enhanced production of the antiviral cytokine Vago5 and antimicrobial peptides (AMPs) upon subsequent WSSV challenge. Furthermore, H3K27ac directly activates key glycolytic genes (Hk2, Pk, Ldh), creating a feedforward loop that sustains metabolic reprogramming. Our work reveals a conserved KAT8-H3K27ac axis driving trained immunity in invertebrates through integrated metabolic-epigenetic crosstalk, analogous to mammalian systems. These findings provide a crucial theoretical foundation for developing antiviral vaccines and sustainable immunostimulants to control disease in shrimp aquaculture. Molecular analysis of virus-trained shrimp reveals that KAT8-mediated H3K27ac drives antiviral memory through metabolic rewiring and Dorsal transcription factor activation, enhancing production of interferon-like Vago5 and antimicrobial peptides.