Abstract Upon infection with Bluetongue virus (BTV), an arthropod-borne virus, type I interferon (IFN-I) is produced in vivo and in vitro. IFN-? is essential for the establishment of an antiviral cellular response and most if not all viruses have elaborated strategies to counteract its action. In this study, we assessed the ability of BTV to interfere with IFN-? synthesis and identified the non-structural viral protein NS3 as an antagonist of the IFN-I system.