Understanding RNA packaging signals in foot-and-mouth disease virus (FMDV) for improved vaccine production

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Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of livestock affecting both the developed and developing world. One of the world's biggest challenges is to meet a growing demand for food. Animal viruses such as FMDV have a significant negative impact on productivity of the livestock industries. Thus improved control of FMD could sustainably improve the performance of global livestock industries and have enormous economic and social value worldwide especially in developing regions where livestock are seen as a means to raise millions from poverty. FMDV is composed of a 'blueprint' for making new virus, enclosed within a protective protein shell or capsid. The blueprint is a single piece of RNA, similar to the DNA genetic code in humans. When FMDV replicates, it uses the RNA blueprint and host cell machinery to make new proteins and new copies of the RNA. The proteins assemble together to make new virus capsids. The RNA is a single linear molecule, like a long piece of string but it all ends up miraculously 'packaged' inside the capsid in a neatly folded ball. How this happens is not understood. We have discovered that there are parts of the RNA that might act as hooks to help the RNA grab hold of the virus proteins. This might guide the folding of the RNA into the correct shape for it to be enclosed by the assembling proteins. This is exciting because people have been wondering about how this works for decades and now we are getting close to finding out. We would like to determine what the hooks are on the RNA and how they grab onto the proteins. This is a critical part of the virus life cycle for FMDV and many other related viruses. We believe the work we propose will provide detailed new understanding of the genome packaging process so that we will be able to reprogramme the viral blueprint to improve on the production of FMD vaccines by increasing yield and/or stability of vaccine.