New research from The Pirbright Institute in the U.K. shows that different populations of foot and mouth disease (FMD) virus swap sections of genetic material at a far higher rate than originally thought. The information will help scientists understand how the frequency of these changes can shape virus evolution and cause new FMD outbreaks.
Pirbright said experts previously believed that FMD virus evolution was driven mainly 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 FMD viral strains and then examining changes in regions of the genomes that code for proteins in the FMD virus 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 recognizing the virus, allowing it to "escape" and potentially cause a new outbreak, Pirbright said.
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 FMD variants are most likely to be created soon after an animal becomes infected. These results align with previous Pirbright research that demonstrated that persistently infected African buffaloes are unlikely to generate new FMD virus variations and cause new outbreaks.
Pirbright said this is important because African buffaloes 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,” Pirbright Institute director Bryan Charleston said. “This tells us that recombination is a major driver of FMD viral evolution, and understanding the mechanisms that determine how new strains are generated could help researchers analyze emerging FMD outbreaks in the field.”
Despite recombination events occurring more often than expected, the team noted that the majority of new FMD 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 who 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, the institute said.