A contrastive study of signaling in CCO and fathead minnow (FHM, an NNV-nonpermissive cell) using RNAi knockdown or dominant negative mutant overexpression verified that ProA-mediated IFN activation went through retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) pathway (RIG-I/MDA5-MAVS-TRAF3-TBK1-IRF3) while NOD1-RIPK2-NFκB and TLR3-TRIF branches were unnecessary. Here, TLR3 is linked to central core myopathy.