London School of Hygiene & Tropical Medicine

Researchers at the London School of Hygiene & Tropical Medicine have developed the first totally man-made live and replicating Bluetongue virus (BVT), a disease that affects livestock and kills about 70% of infected animals.

The discovery, published in the journal Proceedings of the National Academy of Sciences (PNAS), has the potential to lead to the development of more efficient vaccines for Bluetongue and to a better understanding of the way viruses assemble themselves, positively influencing the research into other vaccines.

Professor Polly Roy, who led the team (funded by Biotechnology and Biological Sciences Research Council (BBSRC) and the US National Institute of Health), says: "We've developed the tools and provided the instruction manual for developing new, more effective Bluetongue vaccines. This will not only be useful for combating Bluetongue but will provide insights into fundamental virus assembly that will be useful for producing vaccines for other viruses."

The group led by Prof Roy worked out the precise sequence in which the single components of the virus have to be added to promote the assembly of the functioning structure; adding the components in any different order results in random aggregates and inactive forms of the virus.

Professor Roy continues: "Bluetongue is an important virus to study because it poses such a threat to livestock farming, but it presents some considerable scientific challenges. By virus standards Bluetongue is quite architecturally complex and it has a relatively difficult genome to work with, so assembling it in a test tube was a significant challenge. No one had been able to get such a complicated virus to assemble outside a cell before."

Explaining the major challenges of the project, she says: “Certain protein constructs required for the virus to be active, need to fold in a specific way and that does not happen just by mixing two proteins together, they need to be synthesised in situ together for the assembly to take place.”

This new approach provides an assembly kit for the virus which could allow scientists to design vaccines with useful properties. Developing a vaccine that is tagged with a marker, for example, would make it easier to tell the difference between animals that have been vaccinated and those that have suffered the disease.