Recovery of Bluetongue Virus from nucleic acid: configuration optimisation and application

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Bluetongue is a viral disease of sheep (sometimes cattle and goats) that poses an economic threat to UK agriculture. Since 1998, outbreaks of Bluetongue have spread Northwards in Europe and last year the disease reached Holland. The problem of BTV is clearly growing and the use of modern genetic methods to improve vaccines as well as to understand every aspect of the replication cycle is required. A significant bottleneck however, is the inability to recover BTV from sequence defined clones. As a result, the ability to change or delete essential genes in the virus with a view to producing attenuated strains as candidate vaccines is currently impossible. This project seeks to rectify this and produce a 'reverse genetics' system for BTV. Within the last year the research team has discovered a way to recover Bluetongue virus starting from just the viral genetic material isolated from the virus. The proposed research builds on this success to test ways in which the virus can be constructed completely from cloned gene copies and then deliberately weakened to make better vaccines. The research will specifically target the strain of virus that was the cause of last year's outbreak in Holland to make new strains that can be used to protect UK livestock against this disease. If successful it may be possible to also apply the research to make better vaccines for other viruses which cause disease in human and horses.