Bluetongue virus NS4 protein is an interferon antagonist and a determinant of virus virulence

In this study we show that a non-structural protein of BTV (NS4) is critical to counteract the innate immune response of the host. Infection of cells with a BTV mutant lacking NS4 results in increased synthesis of IFN-ß and upregulation of interferon stimulated genes. In addition, we show that NS4 is a virulence factor for BTV by favouring viral replication in sheep, the animal species most susceptible to bluetongue.