In this study, we infected 129sv IFNAR (2/2) mice with either BTV-1, BTV-8 or the corresponding DNS4 mutants. No major differences were observed in the virulence of wild type and DNS4 viruses; all viruses employed in this study killed 100% of the inoculated mice by day 8 post-infection ( Figure 9 ). We also inoculated 3-day old NIH-Swiss mice intracerebrally with the same viruses as above. Once again, both wild type and DNS4 viruses were able to kill 100% of the inoculated mice with no major differences in the virulence observed ( Figure 9 ).