Influenza A virus NS1 and PI3 Kinase: A structural investigation of their biological interaction

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Influenza A viruses are responsible for serious human and animal diseases, causing seasonal outbreaks and, more rarely, worldwide pandemics, the ?swine flu? being the latest example. Influenza A viruses are relatively simple viruses, making only a few virus proteins. One of these proteins, termed NS1, is not essential for virus replication (growth) in the laboratory but is required for the virus to establish infections in people or animals. It has multiple functions, including counteracting the infected individuals (host) defences against viruses, and in promoting virus replication. To perform these functions the NS1 protein has to interact with many host cell proteins. The aim of this work is to further define how the NS1 protein performs these functions by determining the shape of the protein, defining which parts of NS1 are responsible for its binding to specific host cell proteins, and to better define what roles these different interactions play during the life cycle of the virus. Using the information gained from these studies may pave the way to development of novel anti-viral drugs (which would work by blocking the function(s) of NS1) and the improvement of vaccine design. Indeed, in collaboration with the MRC Technology, part of these proposals are concerned with developing and using screens to identify compounds that interact with NS1 and which have anti-viral activity that may be subsequently developed as anti-influenza virus drugs.