Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an "arbovirus" transmitted from infected to susceptible hosts by biting midges. Historically, bluetongue has been endemic almost exclusively in temperate and tropical areas of the world. However, in the last decade BTV has spread extensively in several geographical areas causing a serious burden to both animal health and the economy. BTV possesses a double-stranded RNA segmented genome. For over two decades, it has been widely accepted that the 10 segments of BTV genome encode for 7 structural and 3 non-structural proteins. In this study we discovered that BTV expresses a previously uncharacterized non-structural protein that we designated NS4. Although BTV replicates exclusively in the cytoplasm, we found NS4 to localize in the nucleoli of the infected cells. Our study shows that NS4 is not needed for viral replication both in mammalian and insect cells, and in mice. However, NS4 confers a replication advantage to BTV in cells in an antiviral state induced by interferon. In conclusion, we have elucidated a possible route by which BTV can counteract the defences of the host.