Genus: Aphthovirus


Genus: Aphthovirus

Virion

Morphology

The crystal structures of several FMDVs and ERAVs have been resolved (Fry et al., 2005, Tuthill et al., 2009). The capsid of FMDV is thin-walled (mean thickness ca. 33 Å), and has an unusually smooth surface. A long (17-23 aa), mobile loop, the G-H loop, projects from the surface of 1D. There is a pore at the 5-fold axis, where part of the underlying 1C is exposed. Some serotypes of FMDV accumulate empty capsids.

Physicochemical and physical properties

Virions are acid labile; FMDV particles are unstable below pH 6.8; equine rhinitis A virus (ERAV) particles are unstable below pH 5.5. The buoyant density in CsCl is 1.43-1.45 g cm-3. Virions of FMDV sediment at 146S, empty capsids at 75S.

Nucleic acid

Genome length (Forss et al., 1984, Carroll et al., 1984, Li et al., 1996, Wutz et al., 1996, Hollister et al., 2008, Hause et al., 2015): 7250-8203 nt (5'-UTR: up to 1112 nt; ORF: 6657-7020 nt; 3'-UTR: 32-110 nt). There is a poly(C) tract close to the 5′-terminus of the genome. In FMDV genomic RNA, it is located about 360 nt from the end, and varies in length from 100 to more than 400 nt. Current data suggest that the poly(C) tract in ERAV genomic RNA is shorter (ca. 40 nt) and closer to the 5′-end. In the RNA of FMDV there is a series of 3-4 pseudoknots on the 3′-side of the poly(C); in ERAV RNA these pseudoknots are upstream of the poly(C) and are formed by perfectly repeated sequences each consisting of 21 bases; the total 5′-UTR is thus extremely long. No pseudoknots have so far been identified in the RNA of bovine rhinitis viruses. The IRES is of type II. The FMDV cre is located in the 5' UTR between the repeated pseudoknots and the IRES, but has not been identified for the other aphthovirus species. ERAV and FMDV differ by approximately 50% in nt sequence across the entire genome.

Genome organization and replication

Genome layout:

VPg-5'UTRIRES-II[Lpro/1A-1B-1C-1D-2Anpgp/2B-2C/3A-3B1-(3B2-3B3)-3C-3D]3'UTR-poly(A)

The deduced polyproteins have lengths ranging from 2,218-2,339 aa. Translation starts at two alternative in-frame initiation sites, resulting in two forms of the L protein (Lab and Lb). L is a papain-like cysteine proteinase which cleaves itself from the virus polyprotein. The 2A polypeptide is very short (chain length = 18 aa in FMDV), and is involved in NPGP-dependent polypeptide chain interruption at its C-terminus. The genome of FMDV encodes 3 species of VPg while those of ERAV, BRAV and BRBV encode only one.

Antigenicity

Seven types of FMDV (A, O, C, SAT 1, SAT 2, SAT 3, Asia 1), two types of BRAV and five types of BRBV have been described by serologic and genetic means. Up to five independent antigenic sites have been reported in FMDV type O virions, two of which have determinants in the G-H loop of 1D.

Biology

This genus is comprised of viruses which primarily infect via the upper respiratory tract. FMDV infects mainly cloven-hoofed animals, but has been isolated from at least 70 species of mammals. Clinical manifestations of FMDV infections include foot-and-mouth disease (vesicular lesions), sometimes with associated acute fatal myocarditis in young animals. ERAV causes upper respiratory tract infections of horses, but may infect a number of other species including man. Bovine rhinitis A virus (BRAV) and bovine rhinitis B virus (BRBV) infect the respiratory tract of cattle. FMDV and ERAV may produce persistent upper respiratory tract infections. FMDV infects cells by binding to integral membrane proteins of the integrin family through its 1D G-H loop; the principle integrin used is αvβ6. Heparan sulphate proteoglycans may also serve as receptors in cell cultures and at least one other unidentified receptor has been proposed. ERAV can use sialic acid to bind to cells. Cap-dependent translation of host mRNA is inhibited by Lpro, which cleaves the host eIF-4G.

Species demarcation criteria

Members of a species of the genus Aphthovirus:

  • share greater than 70% aa identity in the polyprotein,
  • share greater than 60% aa identity in P1,
  • share greater than 80% aa identity in 2C + 3CD,
  • share a natural host range,
  • share a common genome organization.

The divergence (number of differences per site between sequences) of known Aphthovirus species ranges from 0.54-0.65 for P1 and 0.4-0.56 for 3CD.

Member Species

SpeciesVirus name(s)Exemplar isolateExemplar accession numberExemplar RefSeq numberAvailable sequenceOther isolatesOther isolate accession numbersVirus Abbreviation(s)Isolate Abbreviation
Bovine rhinitis A virusbovine rhinitis A virusSd-1KP236128Complete coding genomeBRAV
Bovine rhinitis B virusbovine rhinitis B virus 1EC11EU236594NC_010354Complete genomeBRBV-1
Equine rhinitis A virusequine rhinitis A virusPERV-1DQ272578Complete genomeERAV
Foot-and-mouth disease virusfoot-and-mouth disease virus OO6AY593829Complete genomeFMDV-O

Virus names, the choice of exemplar isolates, and virus abbreviations, are not official ICTV designations.
Download GenBank/EMBL query for sequences listed in the table here.

Derivation of names

Aphtho: from Greek aphthae, "vesicles in the mouth"; English: aphtha, "thrush"; French: fièvre aphteuse