Here, we found that viral mRNA wsv271 could be packaged by EVs secreted by haemocytes during WSSV infection in mud crab, and delivered to the neutrophil‐like 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 signal pathway and further facilitate PAD4 phosphorylation and nuclear translocation to mediate histone‐H3 citrullination, which eventually activated NETosis‐like response in haemocytes to suppress the spread of viral infection. The gene discussed is MAPK1; the disease is viral infectious disease.