Nelson Bay orthoreovirus (NBV) is the prototypic member of the Pteropine othoreovirus family. Previous work in our laboratory has shown that mouse fibroblast cells are capable of restricting the replication of NBV, in vitro, compared to other mammalian cells. The mechanism involves suppressing viral induced cell fusion (termed syncytia). Here, we investigate this unique host-pathogen interaction further using an integrated transcriptomic and proteomic approach. Employing RNA sequencing and SILAC, the gene and protein expression profiles of mouse fibroblast and immortalised bat kidney cells following NBV infection was assessed.

The evaluation of the gene and protein expression data demonstrate that mouse fibroblasts respond to NBV through a robust type I interferon response. We show that knockdown of the type I interferon receptor (IFNAR1) results in an increase in NBV replication and in syncytia formation in mouse fibroblasts. In contrast, stimulation of type I interferon signalling in bat cells with recombinant interferon decreases viral replication. Our results suggests type I interferon signalling plays a crucial role in mediating NBV replication and viral induced cell fusion. We are currently investigating which element of the broad type I interferon signalling pathway is involved in mediating this interaction between mouse fibroblast cells and NBV.

By understanding the molecular mechanisms that influence NBV replication, antiviral strategies may be applied to other fusogenic orthoreoviruses.