The host innate immunity limits the zoonotic potential of animal viruses. (360G-Wellcome-099829_Z_12_Z)

Mammalian cells possess a variety of sophisticated antiviral mechanisms that sense an incoming virus and trigger secretion of type I interferon (IFN-? and IFN-?) and type III interferon (IFN- ). The IFN response is the keystone of the host "innate" immunity against virus infections and results in the rapid expression of hundreds of IFN-stimulated genes (ISGs). Viruses have developed several strategies to cope with the host innate immunity. Interestingly, the vast majority of viruses that circulate in human populations originate from animals. However, crossing the species barrier is a significant hurdle for viruses to overcome. We hypothesise that in many cases the "jump" of an animalvirus to the human population is halted by human ISGs. In this project, we will investigate the anti-viral properties of a library of human ISGs against bluetongue virus (BTV) and African horse sickness virus (AHSV). We will selectthe human ISGs that have a major effect on BTV replication and obtain their sheep orthologs. Subsequently, we will compare the effect of human and sheep ISGs on BTV and AHSV replication. Our hypothesis is that human ISGs strongly inhibit replication of BTV and AHSV while sheep ISGs will be more effective in limiting AHSV than BTV.