To date, limited information is available on the interplay between BTV and the host innate immune system. BTV has been recognized as a potent inducer of type I IFN in sheep [42] , cattle [43] and mice [73] . However, limited data have been available on how BTV induces the IFN response of the cell and, more importantly, what counteracting measures the virus utilises to overcome this response. Our data suggest that BTV may use NS4 to defend itself from the innate immune response of the host given that replication of BTV8-DNS4 in cells treated with IFN is 10 to 25 fold less efficient compared to wild type BTV-8. In addition, the cytopathic effect in cells treated with IFN is more pronounced when cells are infected by wild type BTV-8 compared to cells infected by BTV8-DNS4.