New research from The Pirbright Institute has shown that different populations of foot-and-mouth disease virus (FMDV) swap sections of genetic material at a far higher rate than originally thought. The information will help scientists to understand how the frequency of these changes can shape virus evolution and cause new outbreaks of foot-and-mouth disease (FMD).
It was previously believed that FMDV evolution is mainly driven by mutations caused by small copying errors that accumulate in the RNA genome of the virus when it replicates, known as substitutions. However, in a new study published in PLOS Pathogens, Pirbright scientists have shown that mutations caused by viral recombination events, where different FMD viruses infecting the same animal swap sections of their genome, occur almost as often as substitutions.
The researchers were able to show that these recombination events occur by inoculating African buffaloes with two similar FMDV strains and then examining changes in regions of the genomes that code for proteins in the FMDV outer shell, called the capsid. The host immune system targets capsid proteins to control infection, but changes in those proteins can sometimes prevent the immune system from recognising the virus, allowing it to ‘escape’ and potentially cause a new outbreak.
The study also revealed that levels of recombination were up to 40 times higher in the initial phase of infection compared to later on during the persistent phase, indicating that new variants of FMDV are most likely to be created soon after an animal becomes infected. These results align with previous Pirbright research that demonstrates persistently infected African buffaloes are unlikely to generate new FMDV variations and cause new outbreaks. This is important because African buffalo act as a reservoir for FMD, carrying the virus for years without presenting clinical signs.
“The number of recombination events we saw between the two viruses used in this research was surprising”, said Professor Bryan Charleston, Director of The Pirbright Institute. “This tells us that recombination is a major driver of FMDV evolution and understanding the mechanisms that determine how new strains are generated could help researchers analyse emerging FMD outbreaks in the field.”
Despite recombination events occurring more often than expected, the team noted that the majority of new FMDV variants generated in buffalo were unlikely to evade the immune system. However, those that do escape can cause outbreaks that spread rapidly, as susceptible animals with existing immunity to the original strain are no longer protected. For example, Pirbright scientists recently provided evidence that recombinant FMD viruses caused a series of outbreaks that radiated out from the Indian subcontinent.
As well as being detrimental to animal health and wellbeing, FMD places a huge burden on people that rely on susceptible animals as a source of food and income. Outbreaks of FMD can also disrupt entire trade systems, which incurs large economic costs. Understanding the factors that cause outbreaks is therefore extremely important and this research indicates that the role recombination plays in driving FMD prevalence should not be underestimated.
This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI) and the Wellcome Trust.
Image: Genetic differences between FMD viruses cause variation in capsid proteins, shown by red dots. Taken from the PLOS Pathogens paper.