It has been documented (16, 29) that the immune response, related to the IFN and ISG15 protein activity, inhibits viral infections although in RBCs of the RBIV-infected rock bream (O. fasciatus), proteins associated with the ISG15 antiviral mechanism, such as the IRF3 (interferon regulatory factor 3), NUP35 (nucleoporin 35), and TRIM25 (tripartite motif containing 25), were decreased (16). This evidence concerns the gene ISG15 and viral infectious disease.