Foot and Mouth Disease Virus: Genome Organization, Antigenic Variation, and New Approaches to a Safe Vaccine

Foot and Mouth disease viruses (FMDV), or aphthoviruses, are picornaviruses which are the causative agents of an aggressive and economically important disease of clover-footed farm animals. Their virion contains a single-stranded RNA genome of about 8 kb with a small protein (VPg) covalently attached to its 5′-end, an internal poly (C) tract, and a poly(A) sequence at the 3′-end (Fig. 1). This RNA is of positive polarity and can act directly as a messenger RNA. Protein synthesis involves post-translational cleavage of a 260 K polyprotein which is encoded between a major translation initiation site next to the poly(C) tract and the 3′-end of the RNA. This mode of protein synthesis is common to all picornaviruses and makes them interesting model systems for studying the mechanisms of translation initiation and of protein maturation by specific proteolytic cleavages. Another subject of intensive research concerns the molecular mechanism of the rapid variation of neutralizing antigenic determinants on the FMDV capsid proteins which causes considerable problems in vaccination programs.