Ratinier et al. (2011) showed that NS4 expression is not essential for BTV replication and confirmed the localization of NS4 in the nucleoli during infection. A reverse genetic BTV-8 lacking NS4 was attenuated in sheep when compared to infections with a counterpart that expressed the protein (Ratinier et al., 2016), thus indicating that NS4 modulates host immune responses. The gene discussed is SOS1; the disease is infection.