The interaction of paramyxoviruses with the interferon system. (360G-Wellcome-087751_B_08_Z)

Whilst much has been learnt over recent years about how viruses interact with the interferon (IFN) system, there are still significant gaps in our knowledge. By building upon our extensive experience on the interaction of paramyxoviruses with the IFN system we propose to address some of these questions. More specifically, we will continue to characterise the nature of (paramyxo)virus inducers of IFN and how the IFN-induction cascade is activated and controlled, with particular reference to obser ved heterocellular nature of IFN induction. We will also identify the IFN-induced genes that affect the replication of paramyxoviruses (in particular PIV5), and detail how these viruses deal with cells in a pre-exisitng IFN-induced anti-viral state. In this regards, the importance of virus cytoplasmic bodies to the life-sytle of these viruses and their ability to establish prolonged/persistent infections will be examined. In addition, we will develop generalised methods for the rapid selection o f viruses that are either good inducers of IFN or cannot block IFN signalling, both for our fundamental studies and because such viruses may be developed as potential attenuated vaccine candidates. Such procedures may be particularly valuable for newly emerging viruses that pose an immediate threat to human and animal welfare.