Understanding a viral polymerase complex: a multienzyme 'molecular motor' that drives virus replication

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Viruses can only successfully infect animals by hijacking normal cellular functions and using these to make many more copies of the virus. However, cells do not contain all of the machinery necessary to copy the virus genes, and so the virus has to carry some of this with it when it infects the animal. As this part of the virus has no cellular equivalent, but is necessary for the virus to reproduce, it is a very good target for medicine that interferes with virus infection. Bluetongue virus causes a devastating disease in sheep where up to 70% if infected animals die. For this virus we know all of the genes in the virus, understand the overall structure of the pathogen, and have demonstrated the function of some of the parts of the machinery that copies the virus at a test tube level. What we do not know is precisely how these individual pieces of the machinery work together and that is the focus of this research study. The approach taken will involve a study of the structure of the machinery at a very small scale, as well as experiments that test how well each part of the overall machine is working. Outputs from this research will provide opportunities for the design of new medicine that interferes with the virus machinery and prevents it from copying itself.