Unravelling a tangle: how segmented double-stranded RNA viruses package their genome

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Viruses are obligate parasites and the viral genome is the most important component in keeping a virus alive. Once viruses infect a host cell (human, animal, plant or fish) they must replicate, i.e. make copies of their components and assemble into viable progeny viruses in order to spread. This process of virus synthesis is only possible if the viral genome is incorporated into the new progeny in the correct form. It is particularly difficult for viruses to incorporate the genome if it is in multiple pieces, which is often the case in many viruses (e.g. influenza virus). Understanding how these multiple pieces of genes, each carrying different messages, are incorporated in the correct order and form is essential to understanding how viruses multiply and spread. The lack of this information has created a bottleneck in the research and understanding of many viruses over the years. Therefore this project will focus on animal viruses, particularly Bluetongue virus (BTV) of sheep, which is primarily characterized by its 10 pieces of genes that are not DNA but RNA molecules or segments, each representing a single gene and each generating specific viral proteins. We are exceptionally positioned at the forefront of this field of research. In previous BBSRC funded projects, we have developed unique tools, techniques, reagents and a series of novel assay systems that have already defined some of the essential steps of how BTV may recruit their segments and assemble into a viable virus, competent for spreading. The precise nature of selection and packaging, that is acquiring a single copy of each of ten segments rather than multiple copies of one, is a complex and highly regulated process as the virus must differentiate between cellular and viral genes. We will take advantages of our tools and assays as well as some of the cutting-edge methods that have been developed only recently by other scientists. We will define this poorly-defined complex process to provide information on how BTV and related viruses package their genes and utilise our own methods and expertise in combination with the other biological and physical sciences through collaboration with experts.Long term improvements in animal welfare underpinned by basic research into the pathogen concerned are important. BTV is highly pathogenic in certain livestock and has recently emerged in the UK and Europe. Understanding these vital basic processes in the life cycle of the viral genome will make it possible to develop novel, safer designer vaccines for Bluetongue disease and may be other viral diseases that affect livestock. The data will also allow for the development of novel interventions to improve future disease management.