Leaderless FMDV is fully attenuated in vivo and unable to establish persistent infection
Résumé
Many ways of attenuation of foot-and-mouth disease virus (FMDV) have been ex-plored. One successful method is the deletion of most of the coding sequence for the Leader proteinase Lpro. Lpro inhibits host cell mRNA translation and blocks the interferon response which promotes viral replication. Therefore, leaderless FMDV can replicate in vitro but is strongly attenuated in vivo. The ability of a leaderless variant of FMDV to establish persistent infection after simulated natural infection remains unexplored. We created a variant of FMDV O/FRA/1/2001 lacking Lpro and exposed cattle by intranasopharyngeal inoculation. The animals were observed for 35 days after exposure to determine if leaderless FMDV could establish a persistent infection in epithelia of the nasopharynx, similar to what is seen after wildtype FMDV infection. Despite its ability to replicate well in various cell lines, the leaderless virus was unable to cause an acute infection characterized by vesicular lesions and viral shedding nor establish persistent infection in pharyngeal tissues.