Foot-and-mouth disease virus

The foot- and - mouth disease virus ( FMDV abbreviated in German also FMDV) is a highly contagious viral species from the family of Picornaviridae, together with the Equine rhinitis B virus, forms the genus Aphthovirus and shows a high mutation rate. The FMDV is the causative agent of foot-and -mouth disease in cloven-hoofed animals, in particular in domestic cattle.

• 2.1 Host range
• 2.2 stability

Properties

Morphology

The virion of FMDV is 23 to 27 nm in size in diameter and has an unusually smooth surface for picornaviruses. The 3.3 nm thin-walled capsid is comprised of capsomeres consisting of the four capsid proteins, of which the capsid proteins 1A, 1B, and 1D constituting the outside surface, and are, on the other hand the protein 1C lining the interior of the capsid. The capsid proteins of FMDV are of a size from 208 to 220 amino acids to the smallest of the picornaviruses. At the corners of the capsid, in which a five-pointed symmetry exists ( pentamer ), and the 1C is externally accessible. The capsid protein 1D has an outwardly domain 17-23 amino acids in length, the so-called GH loop, with which the virus recognizes its target cell and infected via membrane receptors of the integrin family of cell. The GH loop carries at its end, the conserved RGD integrin recognition motif.

For serological properties of FMDV capsid protein 1A is mainly responsible for binding to the well neutralizing antibodies. Two determinants are located in the GH loop of 1D. In some isolates can be found much empty, i.e. RNA-free and thus non-infectious capsids (75 -S- component ), but which have the same properties as the serological complete virions (140 -S- component). They probably play a certain role in the diversion of the immune system.

Genome

The genome of the FMDV is about 8450 nt in size and codes for a polyprotein of 2332 amino acids in length. The viral ( ) ssRNA can be read directly as mRNA and is without any intermediate steps to increase operational. Before the start codon of the single open reading frame (ORF ) is a non-coding region (5'- NCR), which is approximately 1200 to 1500 nt almost twice as long as with other picornaviruses. The size stated, inter alia, to a depending isolate 100-400 nt long poly - cytosine tract (poly -C) in the front third of the 5'- NCR which forms a plurality of secondary structure as a pseudoknot. To the 5 ' NCR three different genomic viral proteins ( VPg ) covalently linked.

The reading frame of the FMDV does not start, as in all species of the genus Aphthovirus and cardio virus with the capsid proteins, but by a so-called leader protein ( L protein ), which has a protease function. Translation of the ORF starts at the FMDV at two alternative start codons, thereby producing two different lengths L proteins are formed ( Lab and Lb). Is initiated the translation as with all picornaviruses by an IRES. The LB protein is now in a position to be activated by cleavage of a cellular protease that initiates the degradation of a cellular protein ( p220 ) that in turn is part of the cellular translation initiation complex of eIF- 4F. Characterized the used of the cellular mRNA translation is prevented by means of a 5'- cap structure and blocking the total cellular protein synthesis; only the virus containing the factor eIF -4F is not required because of its IRES can now synthesize its proteins. It also speaks of a so-called "virus -host shutoff " (disabling the host cell by the virus ). In addition to the SB protein and the protease of the FMDV - C3 is able to inactivate cellular initiation factors.

Biological Properties

Host range

A natural infection with FMDV is described in many even-toed ungulates and other mammals, so mainly in bovids ( Bovidae with the key representatives buffalo, bison, antelopes, gazelles, cattle, sheep and goats), but also in deer ( Cervidae ), peccaries ( Tayassuidae ), pigs ( Suidae ), hedgehogs ( Erinaceidae ), camels ( Camelidae ), giraffe -like ( Giraffidae ), long-tailed mice ( Muridae ), elephants ( Elephantidae ), bears ( Ursidae ) and tapirs ( Tapiridae ). On the basis of genetic studies of FMDV isolated from wild animals can its spread be shown by large animal migrations, especially in Africa. The FMDV also allows conclusions on the migration routes of the herds. Under experimental conditions, the FMDV is also applicable to dogs, cats, rabbits and rats. In the research, the artificial infection of guinea pigs and newborn mice of importance. The virus can be very good in cell lines derived from hamster kidney (BHK -21: baby hamster kidney cells ) are grown; also for the production of the vaccine against FMDV types, this cell line will be used.

Stability

Due to the capsid via a few polar amino acid groups that FMDV is highly sensitive to acids and is already inactivated at pH values ​​below 6.8. Whereas the normal maturing of meat (pH < 6.0) and occurring in dairy products made from sour milk acidification inactivates the virus as completely as the normal stomach acid. Therefore, transmission of the virus via the gastrointestinal tract is excluded. However, spreading of virus in products that are not subject to acidification (bone marrow, fat, fat, blood and frozen meat ) is possible. The virus is not inactivated by low temperatures and high salt concentration. In dry environment, the FMDV over time is very stable. Especially dried- saliva allows the spread by the wind over distances greater than 10 km, when dry climatic conditions are given.

Subtypes and dissemination

The FMDV is distributed worldwide except in New Zealand, Australia and North America. In many parts of Asia and South America and most African countries the virus is endemic. In Europe komt due to animal health intervention and prophylactic vaccination before only in sporadic outbreaks. The FMDV has a high antigenic variability, and it was a large number of different serotypes, strains and variants isolated. These differ in their serological and immunological properties. The first two types - and thus the so-called pluralism of the virus - have been characterized by Vallée and Carré in 1922 and named after the location of the isolate as O (Oise ) and A ( Ardennes ). In Germany, a third type (C ) 1926 and 1952 were discovered three other types in Africa ( " Southern African Territories " SAT ) can be isolated. The last type described so far in 1954 in Asia isolated ( ASIA1 ). All types except the FMDV -C tend to variability and formation of other subtypes, which in addition to a type antigen yet another tribe specific antigen. While all types are well distributed geographically different, the type O FMDV is present in all FMDV areas.

• Species foot-and - mouth disease virus ( FMDV )

• Type foot- and - mouth disease virus A ( FMDV -A), 32 subtypes
• Type foot- and - mouth disease virus Asia 1 ( FMDV ASIA1 ), 3 subtypes
• Type foot- and - mouth disease virus C ( FMDV -C)
• Type foot- and - mouth disease virus O ( FMDV -O ), 11 subtypes
• Type foot- and - mouth disease virus SAT 1 ( FMDV- SAT1), seven subtypes
• Type foot- and - mouth disease virus SAT 2 ( FMDV SAT2 ), 3 subtypes
• Type foot- and - mouth disease virus SAT 3 ( FMDV SAT3 ), 4 subtypes