Foot-and-mouth disease: a step closer to understanding the persistence of the virus in ruminants
Foot-and-mouth disease is one of the most contagious viral animal diseases. It affects more than 70 domestic and wild species, in particular cattle, pigs, sheep and goats. Disease-free countries are not exempt, as has been shown by recent cases since January 2025 in Germany, Hungary and Slovakia. The disease has a major socio-economic impact on livestock sectors, both in areas where it is endemic and in the event of an incursion into a previously disease-free area. For more than 50 years, a complex question has been asked: in areas where the virus circulates, why is it able to persist in up to 50% of infected ruminants after their apparent recovery? ANSES's Laboratory for Animal Health sought to answer this question through FMDV_PersIstOmics, an international research project. This project revealed that one of the virus's proteins plays a key role in this persistence.
The project entitled "From proteogenomic host response signatures of persistent foot-and-mouth disease virus (FMDV) infection to diagnostic markers and therapeutic control" (FMDV_PersIstOmics) sought to understand the mechanisms behind the persistence of foot-and-mouth disease virus in ruminants, in order to improve diagnosis and develop therapeutic tools. This is important because some ruminants continue to carry the virus even after recovering from the disease. This can last from a few weeks in small ruminants to several years in some species of wild cattle, such as African buffalo. Sandra Blaise-Boisseau, project coordinator and scientist in the Virology Joint Research Unit (UMR) of ANSES's Laboratory for Animal Health explains: " this phenomenon is particularly significant in cattle, where it concerns more than 50% of infected animals. This poses a potential risk of transmission of the virus to other susceptible animals, and also of recombination between strains if the carrier animal is then reinfected."
The project, funded by the first call for projects from the International Coordination of Research on Infectious Animal Diseases (ICRAD), ran from March 2021 to January 2025. It brought together five international partners: ANSES, the Sciensano Institute in Belgium, the Friedrich-Loeffler Institut in Germany, the Swedish University of Agricultural Sciences and the SAP Institute in Turkey.
Role of a viral protein in the persistence of the virus
To gain a better understanding of the mechanisms underlying this persistence, the scientists created a version of the foot-and-mouth disease virus that lacked a key protein, the "Leader" protein, which is known to inhibit the host's immune response. In tests on cattle, they showed the essential role of this protein: the virus cannot persist without it.
"These results confirm those obtained in vitro on bovine cells as part of the same project, and are consistent with the findings of a previous project also coordinated by ANSES's Laboratory for Animal Health", adds her colleague Aurore Romey. "We had observed that in animals in which the virus persisted, the innate immune response was still present, but was insufficient to eliminate the virus. It was as if a balance had been established between the virus and the immune system, where neither could get the upper hand."
As part of the FMDV_PersIstOmics project, the scientists also tested a compound that could potentially upset this balance, thereby preventing or impeding the persistence of the virus. The results will be published shortly.
A virus lacking the Leader protein: a promising approach for developing new vaccines
The "Leaderless" virus was found to have strongly attenuated effects in cattle, as well as being unable to persist, unlike the parental strain. This virus represents a safer alternative to the wild virus for conducting research, developing diagnostic tools (e.g. neutralisation tests) and producing inactivated vaccines at lower levels of biosafety.
This could reduce the cost of producing foot-and-mouth disease vaccines. A live attenuated vaccine developed from this virus is currently being studied as part of the European SPIDVAC project, coordinated jointly by ANSES's Laboratory for Animal Health and the Friedrich-Loeffler Institut.
Understanding circulation of the virus depending on the species
These two organisations are also working together within the European partnership of scientists and funders helping to improve European Partnership on Animal Health and Welfare (EUPAHW), in which they have proposed a project to study the circulation of the virus, its genetic variations and the resulting changes (transmission, clinical symptoms, etc.) depending on the species of animal affected.
Among other things, this research could help explain the cases of infection of water buffalo on a farm in Germany last January, where three animals died of foot-and-mouth disease, even though this disease had not been detected in this country since 1988 and is not usually fatal in healthy adult animals. The study could also help to explain the recent emerging cases of the disease in Central Europe.