The attenuation of FMDV RNA replication. (360G-Wellcome-094898_Z_10_Z)

The body of research into FMDV is impressive; 150+ complete genome sequences, a map of polyprotein processing, full-length cDNA clones from which virus can be rescued ( infectious copies ), a non-infectious replicon cDNA system, characterisation of the virus receptor, atomic structures of the virus particle, L proteinase and 3D polymerase, characterisation of immune responses with detailed epitope mapping. There still remain, however, substantial and critical gaps in our knowledge as to how th is virus replicates so rapidly. Even cursory inspection of the FMDV genome reveals a number of features which are unique to aphthoviruses. Surprisingly, the function or contribution to RNA replication of these features is not understood and is not currently being investigated. Our hypothesis is that these unique genome features are critical targets for genetic modification(s) for vaccine development. Our proposed program of research focuses upon questions concerning the replication of v irus RNA and the molecular interactions between virus RNA/virus proteins with host-cell proteins using the (non-infectious) FMD replicon system. An essential element of this proposal is to harness the knowledge gained for the design of new, recombinant, forms of the genome to produce attenuated phenotypes: candidates for a new form of disease control live, attenuated, vaccines.