Foot-and-mouth disease

Abstract

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease was initially described in the 16th century and was the first animal pathogen identified as a virus. Recent FMD outbreaks in developed countries and their significant economic impact have increased the concern of governments worldwide. This review describes the reemergence of FMD in developed countries that had been disease free for many years and the effect that this has had on disease control strategies. The etiologic agent, FMD virus (FMDV), a member of the Picornaviridae family, is examined in detail at the genetic, structural, and biochemical levels and in terms of its antigenic diversity. The virus replication cycle, including virus-receptor interactions as well as unique aspects of virus translation and shutoff of host macromolecular synthesis, is discussed. This information has been the basis for the development of improved protocols to rapidly identify disease outbreaks, to differentiate vaccinated from infected animals, and to begin to identify and test novel vaccine candidates. Furthermore, this knowledge, coupled with the ability to manipulate FMDV genomes at the molecular level, has provided the framework for examination of disease pathogenesis and the development of a more complete understanding of the virus and host factors involved.

FIG. 1.

Countries in which FMD was reported to the OIE between 1990 and 2002. The data and maps were compiled by Nick Knowles and can be found at www.iah.bbsrc.ac.uk/virus/picornaviridae/aphthovirus.

FIG. 2.

Schematic map of the FMDV genome. The ORF is shown in the boxed area, with the viral proteins named according to the nomenclature of Rueckert and Wimmer (402). Also shown are the functional elements of the genome as described in the text and the partial protein cleavage products. The sites of the primary cleavages and the proteases responsible are indicated. PKs, pseudoknot structures. (Adapted from reference .)

FIG. 3.

Structure of the mature type O₁BFS FMD virion based on X-ray crystallographic data. The structures shown are based on the data of Acharya et al. (2) and Logan et al. (272). (a) A viral protomer highlighting the β-barrel-and-loop organization of the viral proteins. (b) A pentamer positioned on the virion looking down the fivefold axis. (c) The organization of the entire virion, highlighting the G-H loop (yellow) and the RGD sequence (white). Note the pore located at the top of the fivefold axis (see text). (d) A protomer highlighting the positions of the G-H loop (purple) and RGD sequence (yellow). All structures are representative of the mature virion (cleaved VP0 [see text]), and the viral proteins are colored blue (VP1), green (VP2), and red (VP3). VP4 is buried within the particle and is visible only in panel a, where it is colored yellow. The graphic renderings were done by using RasMole.

FIG. 4.

The spread of the PanAsian strain of FMDV type O from its first appearance in India in 1990 until its appearance in the United Kingdom in 2001. Solid colors, PanAsian strain present; cross-hatched colors, type O present and PanAsian strain suspected. The data and map were compiled by Nick Knowles and can be found at www.iah.bbsrc.ac.uk/virus/picornaviridae/aphthovirus.