Following infection with a virus the body mounts innate and adaptive (e.g. antibodies) immune response that are critical in controlling the infection. Immediately following infection, cells begin to respond to viruses by producing a substance called interferon (IFN). The IFN system is an extremely powerful anti-viral response that if it worked as it was supposed to could probably control most, if not all, virus infections in the absence of the adaptive immune response. However, it rarely works correctly because all viruses have ways and means of at least partially circumvent the IFN response. Many viruses do so by producing products (usually proteins) that interfere with different parts of the IFN system. We are particular concerned with better understanding at the molecular level how influenza viruses and paramyxoviruses (e.g. mumps, measles, parainfluenza viruses) circumvent the IFN response. Not only are such studies of fundamental interest they may also point ways forward to better methods of controlling virus infections. For example, by knocking out the ability of a virus to circumvent the IFN response the virus will be weakened and unable to cause disease. However, such weakened (attenuated) viruses if injected will induce an adaptive immune response that will protect from subsequent infection by the natural (virulent) viruses. Thus such IFN-sensitive viruses may be further developed as attenuated virus vaccines. Furthermore, novel anti-viral drugs might be developed which prevent viruses from circumventing the IFN response. 

A major part of our research effort has been involved with studies on the induction of protective immunity to viruses, with the long term aim of producing novel vaccines and anti-viral drugs to a variety of human and animal viruses. In addition, we have an active research programme concerned with exploring the molecular biology of influenza viruses and paramyxoviruses, the latter of which cause a number of important acute human and animal diseases, e.g. measles, mumps, rinderpest, and human and animal respiratory illness. In particular we are interested in determining at the molecular level how these viruses interact with innate intracellular defense mechanisms, including the interferon (IFN) response. Our own work in this area has lead to significant insights into the interaction of viruses with the IFN response.  For example, we were the first group to describe how a simple RNA virus specifically blocked the IFN response by a defined mechanism (targeted degradation of STAT1). We were also the first group to show that mda-5 is a key signalling molecule in an intracellular IFN-induction pathway and that many parmayxoviruses interact with mda-5 to limit IFN production by infected cells. More recently our work on the NS1 protein of influenza viruses showed it not only blocked the interferon response, but it also activated the P3 kinase signalling pathway. Furthermore, these findings have revealed that the way viruses interact with the immune response may be an important factor that limits their ability to cross species barriers and establish persistent infections. Not only are these results of fundamental interest in virology but they also point a way forward for designing and manufacturing attenuated virus vaccines. Thus it may be possible to specifically engineer these viruses to make them sensitive to IFN, thereby rendering them non-pathogenic but highly immunogenic. Using the knowledge we gained from these studies, we have also developed methods for engineering human cells, that are used in vaccine manufacture and virus diagnostics, so that can not respond to IFN. Such IFN non-responsive cells are better able to support the replication of a variety of DNA and RNA viruses, and may thus be useful in vaccine manufacture and the isolation of viruses from clinical material.