From proteogenomic host response signatures of per-sistent foot-and-mouth disease virus infection to diagnostic markers and therapeutic control (FMDV_PersIstOmics)

Foot-and-mouth disease (FMD) is a devastating viral disease of cloven-hoofed animals with severe socioeconomic consequences worldwide. Its causative agent, FMD virus (FMDV), is highly contagious and spreads rapidly in susceptible animal populations. More than 50% of ruminants infected with FMDV will carry the virus in the nasopharyngeal cavity over a long time, which is known as a persistent infection or ‘carrier state’. Carrier animals are often considered a potential source of infection and represent a barrier to international trade. The fear of infection from carriers is a major obstacle to vaccination concepts that can be used in FMD-free areas without culling the vaccinated animals. The mechanisms underlying the persistence of FMD virus are still largely unknown. This knowledge gap needs to be filled in order to predict, prevent, detect or cure FMD persistence and to stop the mass culling of exposed animal populations during outbreaks of the disease in free areas. The project uses a near-natural model of FMD virus persistence in primary bovine soft palate cells, which are cultivated as a multilayer at an air-liquid interface. This model was developed in the EU project ERA-NET/ANIHWA ‘Transcriptovac’. Its use and improvement contributes to the reduction of animal experiments. However, the project also includes experimental FMD virus infection of guinea pigs and cattle, in order to detect changes in the host immune response during persistent infection. Genes that are highly regulated during persistence will be evaluated as candidate diagnostic markers. Furthermore, pharmaceuticals that may prevent the establishment of FMDV persistence or even terminate the infection will be searched. The project involves partners from Belgium, France, Sweden, Turkey and Germany. FLI as the German partner carries out the proteogenomic analyses and animal experiments.