Therefore, the data presented so far suggested that either the BTV-1 NS4 was somewhat defective or that the influence of this protein on viral replication in the presence of IFN varies from strain to strain. In order to discern between these two possibilities, N in position 6) in order to render this protein identical to the homologous BTV-1 protein ( Figure 8B ). Both cytopathic protection assays and multistep growth assays clearly showed that BTV-8/1S9 replicated more efficiently than BTV-8/ 1S9DNS4 in the presence of IFN ( Figure 8C, D) . Similar results were obtained with BTV-8/1NS4, which replicated more efficiently than BTV-8DNS4 in cells pre-treated with IFN, while no major differences were observed between BTV-1/8S9 and BTV-1/8S9DNS4. Collectively, these data strongly indicate that the NS4 of BTV-1 is not defective and can function within the context of BTV-8.