134 A cellular restriction factor blocking replication of an emerging bunyavirus in human cells: clues for cross-species barriers?

Schmallenberg virus (SBV) is a novel orthobunyavirus of ruminants that emerged in Europe in the summer of 2011. Although mild clinical signs are observed in infected adult animals, transplacental infection has been associated with the development of congenital malformations, stillbirths and abortions. SBV has spread dramatically across north-western Europe reaching 100% prevalence in some herds. Despite antibodies against SBV being found in a variety of animal species neither human cases nor positive serology in highly exposed humans have been detected. We have recently developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Specifically we developed a reverse genetics system that aided us in unraveling determinants of virulence. Here, we report identification of a cellular factor that restricts SBV replication. While the human orthologue restricts SBV replication under different experimental conditions, no restriction is observed by the ovine counterparts. We show that the restriction is specific since SBV replication is restored under the presence of a known viral restriction factor antagonist. We also show that this viral restriction factor and SBV nucleocpasid co-localize at the cell membrane and in the perinuclear region and we partially unravel the mechanism of restriction. Based on these results we hypothesize that the lack of positive human serology to SBV is related to the ability of this cellular factor to restrict SBV replication and we are currently exploring if these findings can be extended to other bunyaviruses.