Evasion of antiviral responses in the host cell nucleus

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Understanding the fundamental processes of how viruses are detected when they infect a cell and the defence mechanisms that cells employ to combat such viruses is crucial for improving the health and wellbeing of humans, animals and plants. Many important host defence pathways rely on processes initiated and/or functioning in the host cell nucleus. This research seeks to understand a new pathway we have discovered by which herpesviruses can evade antiviral responses within the nucleus of infected cells. Herpesviruses are highly prevalent pathogens of animals that cause significant disease and economic losses in the horse, cow, pig and poultry industries. Human herpesviruses can also cause severe or life-threatening disease, especially in immuno-suppressed people, and are thought to increase the risk of multiple sclerosis and Alzheimer's disease. Herpesvirus infections are for life - after the initial 'primary' infection these viruses establish a latent infection of their hosts, for example in nerve cells, which is commonly followed by repeated episodes of reactivation over the lifetime of the host, where the virus emerges from its hiding place to cause 'secondary' infections (e.g. cold sores) and spread to new hosts. Because of the high disease-burden caused by herpesvirus infections, there is a clear need to develop new and improved antiviral drugs and vaccines to treat infections with these viruses in animals and humans.The focus of this research is to uncover the details of the new pathway we have recently discovered by which herpesviruses can counteract host defences in cells. This previously unknown pathway involves a complex of two virus proteins, one of which is a conserved protein "kinase", an enzyme that modifies the function of other proteins by attaching a phosphate molecule to them. Will we use state-of-the-art techniques to understand how, why and where specific cellular proteins are targeted and modified by this virus protein complex during herpesvirus infection. Importantly, this research will provide new and important knowledge about antiviral pathways that are effective against a diverse range of different viruses. The new understanding of how viruses interact with their hosts that we will gain from this research will underpin the development of new and improved ways of fighting herpesviruses, as well as many other important viruses, that cause significant animal and human diseases throughout the world.