Key concepts

Figure 1. Panel (a). Life cycle of FMDV within a single cell. The virus attaches to a receptor (e.g. the integrin v6) on the cell surface. It is internalized within a clathrin-coated vesicle (CCV) which fuses with an early endosome, within which the environment is relatively acidic (elevated [H⁺]). These conditions result in capsid disassembly; the viral ribonucleic acid (vRNA) is released and delivered (by an unknown mechanism) to the cell cytoplasm where viral protein synthesis, RNA replication and particle assembly occur prior to cell lysis and virus release. Panel (b). Synthesis of foot-and-mouth disease virus proteins. The virion RNA, which also serves as messenger, is represented by the upper line; the proteins encoded are shown by the boxes beneath. RNA: The 8.5-kb genome is linked at its 5¢ end to a viral protein, VPg (orange circle), also called protein 3B. Cn denotes poly(C), An, the poly(A) tail. The internal ribosome entry site (IRES) directs protein synthesis to be initiated at either of the arrowed positions to produce two forms of the leader (L) protease termed Lab and Lb; these mark the start of the long continuous coding region that occupies nearly all the remainder of the genome. Proteins: The viral proteins are made initially as one long polypeptide (‘polyprotein’). This contains proteases (L, 2A and 3C; filled boxes) that cleave at specific sites () to generate the complete repertoire of viral proteins; P1–2A, P2 and P3 are intermediates in this process. Other functions: viral proteins VP1, VP2, VP3 and VP4 (also called 1D, 1B, 1C and 1A, respectively) make up the protein coat, or ‘capsid’, of the virus (orange triangle is a myristic acid residue linked to the N-terminus of VP4). VPg is encoded in three related forms. Protein 3D is the RNA polymerase that replicates the genome. The protease Lab/Lb also acts as an inhibitor of host protein synthesis.

Figure 2. Structure of foot-and-mouth disease virus. The capsid is built from four viral structural proteins, VP1–4. (a) Shows a mature protomer, the smallest repeating unit, contains one copy of each of VP1–3; Blue, VP1; Green, VP2; Yellow, VP3. Sidechains of amino acids that are targeted by neutralizing antibodies are shown in white on the peptide backbone of the protomer. Upper image is viewed from above; lower image is viewed through the plane of the capsid. (b) The capsid. Five protomers (triangle=one protomer) assemble into a saucer-shaped, pentagonal disc, with VP1 in the centre. Twelve of these pentamers make a complete capsid. VP4 is not shown since it is entirely internal within the capsid.

Figure 3. Panel (a). The foot of a steer with foot-and-mouth disease showing a fluid-filled vesicle between the hoofs just below and to the left of the end of the forceps. Panel (b). Erosions of the mouth resulting from the rupture of vesicles.

Figure 4. Graph to demonstrate time course of clinical signs, virus isolation and antibody production after acute infection, following direct inoculation, of cattle with FMDV. The graph is a pictorial representation of data accumulated from a number of cattle challenge experiments. Cattle usually start showing clinical signs of FMDV within 2–3 days after contact with infected animals; this is depicted as a clinical score which includes the severity of lesions on the mouth and feet and temperature. The changes in rectal temperature above normal are also shown separately. Generally, animals are debilitated for only 4–5 days, when they have a high temperature and newly formed vesicles. Animals with healing lesions, usually from day 7 onwards, are more inclined to eat and move normally unless there are secondary infections of the lesions. Viraemia (virus in blood) is detectable soon after challenge and is maintained for approximately 7 days. Virus is also detectable in the pharynx, when samples are taken with a probang cup, soon after challenge but in carrier animals virus may be detectable in this site for many months after challenge without associated lesions or clinical signs. A specific antibody response to the virus is usually rapidly induced and detectable within the first week after challenge. Details: Blood – The quantity of virus detectable in blood measured as plaque forming units (pfu) per millilitre of blood, typical peak values 10⁷–10⁸ pfu/ml; Clinical signs – A score based on the severity of lesions on the feet and mouth, general demeanour and rectal temperature; Probang – The quantity of virus detectable in probang samples measured as pfu per millilitre of pharyngeal/oesophageal fluid, typical peak values 10⁷–10⁸ pfu ml^–1; Rectal Temp – Peak rectal temperatures of approximately 41°C are routinely measured; Antibody – Anti-FMDV specific antibodies, usually measured as the neutralizing antibody titre, are induced at about 7 days after challenge.