As described in the Introduction, studies with CCHFV have shown it has a delayed IFN response in infected cells [21] . We wanted to know if NSDV/GV is able to interfere with the early induction of type I IFNs. To address this question we transfected Vero cells with a reporter gene construct containing the firefly luciferase under the control of the IFNb promoter. Luciferase expression is taken as a measure of protein production from this specific promoter after activation of transcription, which in turn is taken as a measure of IFNb induction. Although this system is commonly used to study the control of IFN induction, we recognise that failure to express luciferase could reflect viral effects at a number of different points in the induction, transcription and protein synthesis pathway. As a positive control for the induction of IFNb we used Newcastle disease virus (NDV), a paramyxovirus which has been reported as being unable to block IFN induction in mammalian cells [33] and therefore is frequently used as a model stimulator of cytoplasmic PRRs. Vero cells lack a functional IFN-b gene [34, 35] which made them a useful tool for our experiment because they allowed us to measure direct activation of the IFNb promoter in infected cells excluding any indirect effect of IFN synthesis in neighbouring uninfected cells. The transfected Vero cells were infected with the NSDV or GV isolate or with NDV and the amount of synthesised luciferase was determined at the indicated time points ( fig. 1a&b ). Infection with NDV induced a rapid activation of the IFNb promoter ( fig. 1a ); after 4.5 and 6.5 hours of NDV infection very high amounts of luciferase are already detected when compared to mock-infected cells, with levels of luciferase already decreasing at 9hpi. In contrast, at 4.5hpi there was no increase in promoter activity detectable in GV/ NSDV-infected cells when compared to mock-infected cells ( fig. 1b) . A very slight increase in luciferase was seen at 10hpi in NSDV-infected cells, and at 14 hpi there is a clear significant increase in the reporter gene activity induced by NSDV or GV infection with further increases up to 24 hours of infection. Recent evidence suggests that many negative-strand RNA viruses do not generate dsRNA during infection [36] and only induce IFN rapidly if they contain defective interfering particles (DIs) [37] . It is likely therefore that our NDV preparation is acting through a significant content of such DIs. Neither NSDV/GV isolate, however, induced interferon until later stages in the infection cycle. There was a significant difference between the two isolates, NSDV and GV, regarding the kinetics of activation of the IFNb promoter. Activation by the GV isolate was later than that induced by the NSDV isolate and also the transcriptional activation observed was lower when compared to the NSDV isolate ( fig. 1b ). This might be due to the fact that the NSDV isolate was previously passaged over 60 times in cell culture, in contrast to the GV isolate which has primarily been maintained in mouse brain culture and has been passed twice in BHK-21 culture in our hands; this difference may have resulted in the NSDV isolate having a reduced efficiency to evade IFN induction, or a more rapid growth in the cultured cells, leading to a more rapid production of one or more PAMPs recognised by the host cell. This second possible explanation is supported by the growth kinetics of GV and NSDV in Vero cells, which showed that NSDV replication rates were faster compared to GV, although both isolates grew to the same final titer (Lidia Lasecka, pers. communication).