Wolbachia as a defence against RNA viruses in insects. (360G-Wellcome-094664_Z_10_Z)

The bacterial endosymbiont Wolbachia protects insects against viral infections. The aim of this project is to understand this new form of antiviral protection, using Drosophila as a model system. Our results will be relevant for attempts to use Wolbachia to control viral diseases of humans and animals that are transmitted by insect vectors. To understand the causes of this antiviral resistance, we will first determine which stage of the viral replication cycle Wolbachia affects (entry into ce lls, replication, translation or exit). In Drosophila, we will screen for host genes and pathways that are required for the antiviral effects of Wolbachia and examine whether the antiviral protection relies upon the insect immune system or other host pathways. From the bacterium s perspective, we will identify Wolbachia genes up-regulated upon host viral infection and test these for their antiviral effects. Additionally, we will use next-generation sequencing to identify genes associated with n aturally occurring variation in the antiviral properties of Wolbachia. Finally, to see if interventions using Wolbachia will be sustainable, we will test whether viruses can evolve to overcome the antiviral effects of Wolbachia and identify the mutations that underlie these changes.