In summary, the findings of this study indicated that during WSSV infection, viral mRNA wsv271 was specifically carried by EVs and transmitted to the surrounding EVs‐recipient cells, followed by translation into viral protein, and then interacted with the TIR domain of Toll4 to recruit MyD88 so as to activate P38‐MAPK pathway and further facilitate PAD4 phosphorylation and nuclear translocation to citrullinate histone‐H3, which eventually suppressed the spread of viral infection by inducing NETosis‐like response in haemocytes (Figure 8). This evidence concerns the gene PADI4 and viral infectious disease.