Simplified diagram of the stages of the viral cycle regulated by the folding of the NCR of ISAV. For easy viewing, the ISAV genome is represented as a single genomic segment. In the nucleus, the viral genome (vRNA) is transcribed by the RdRp (purple circle) bound to each genomic segment to generate mRNA and cRNA. In the cytoplasm, the ribosomes recognize and scan the 5′ NCR region of the mRNA until the AUG codon to initiate the synthesis of viral proteins, which includes the RdRp necessary for genome replication (synthesis of vRNA) and of the rest of the viral proteins involved in the assembly of the mature viral particle. Continuous lines: stages regulated by NCR; dotted lines: the remaining stages of the viral cycle. The folds adopted by the NCR of vRNA (red line) and cRNA (blue line) are highlighted; in mRNA, the 5′ NCR is shown (green line), including the AUG codons (green circle), and the 3′ NCR is shown, including the poly-A tail (yellow line).