|Title||Turnover rate of NS3 proteins modulates bluetongue virus replication kinetics in a host-specific manner|
|Author(s)||Ftaich, Najate; Ciancia, Claire; Viarouge, Cyril; Barry, Gerald; Ratinier, Maxime; Rijn, P.A. van; Breard, Emmanuel; Vitour, Damien; Zientara, Stephan; Palmarini, Massimo; Terzian, Christophe; Arnaud, Frédérick|
|Source||Journal of Virology 89 (2015)20. - ISSN 0022-538X - p. 10467 - 10481.|
|Publication type||Refereed Article in a scientific journal|
Bluetongue virus (BTV) is an arbovirus transmitted to livestock by midges of the Culicoides family and is the etiological agent of a hemorrhagic disease in sheep and other ruminants. In mammalian cells, BTV particles are released primarily by virus-induced cell lysis, while in insect cells they bud from the plasma membrane and establish a persistent infection. BTV possesses a ten-segmented double-stranded RNA genome, and NS3 proteins are encoded by segment 10 (Seg-10). The viral nonstructural protein 3 (NS3) plays a key role in mediating BTV egress as well as in impeding the in vitro synthesis of type I interferon in mammalian cells. In this study, we asked whether genetically distant NS3 proteins can alter BTV-host interactions. Using a reverse genetics approach, we showed that, depending on the NS3 considered, BTV replication kinetics varied in mammals but not in insects. In particular, one of the NS3 proteins analyzed harbored a proline at position 24 that leads to its rapid intracellular decay in ovine but not in Culicoides cells and to the attenuation of BTV virulence in a mouse model of disease. Overall, our data reveal that the genetic variability of Seg-10/NS3 differentially modulates BTV replication kinetics in a host-specific manner and highlight the role of the host-specific variation in NS3 protein turnover rate.