MicrobiologyBytes

Success of a virus infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. In picornaviruses, virus replication is initiated by the viral polymerase and a viral-coded protein, termed VPg, that primes RNA synthesis. Foot-and-mouth disease virus (FMDV) is exceptional among picornaviruses in that its genome encodes three copies of VPg. Why FMDV encodes three VPgs is unknown.

Researchers constructed four mutant FMDVs that encode only one VPg: either VPg1, VPg3, or two chimeric versions containing part of VPg1 and VPg3. All mutants, except that encoding only VPg1, were replication-competent. Unexpectedly, despite being replication-competent, the mutants did not form plaques on BHK-21 cell monolayers. The one-VPg mutant FMDVs released lower amounts of encapsidated viral RNA to the extracellular environment than wild type FMDV, suggesting that deficient plaque formation was associated with insufficient release of infectious progeny. Mutant FMDVs subjected to serial passages in BHK-21 cells regained plaque-forming capacity without modification of the number of copies of VPg. Substitutions in non-structural proteins 2C, 3A and VPg were associated with restoration of plaque formation. Specifically, replacement R55W in protein 2C was repeatedly found in several mutant viruses that had regained competence in plaque development. The results link the VPg copies in the FMDV genome with the cytopathology capacity of the virus, and have unveiled yet another function of 2C: modulation of picornavirus cell-to-cell transmission. these data highlight the role of non–structural proteins in the adaptability to changing environments during picornavirus infections, with clear implications for viral pathogenesis.

Deletion Mutants of VPg Reveal New Cytopathology Determinants in a Picornavirus. 2010 PLoS ONE 5(5): e10735. doi:10.1371/journal.pone.0010735

Related:

• Foot and Mouth Disease

• 23rd September: A suspected new case of foot-and-mouth is being investigated on the Hampshire-West Sussex border. Bluetongue is confirmed on a farm in Suffolk.

• 21st September: Another case of foot-and-mouth disease was confirmed on a farm in the Egham area of Surrey. Around 40 cattle were culled on the premises, which are within the existing 3km protection zone.

• 18th September: Defra confirms fifth infected premises since the start of the outbreak.

• 14th September: Defra announces that a second farm in Surrey is affected, imposes new protection and surveillance zone and confirms that sequencing tests of the virus have shown it to be type 01 BFS67, the same strain of virus responsible for the August outbreak.

• 12th September: Defra confirms a new case of FMD in Surrey.

• 8th September: The last restrictions imposed on livestock movement in the UK following the foot-and-mouth disease outbreak were lifted, but the earliest the UK can achieve international foot-and-mouth disease-free status is 7th November.

• August 2007: On 3rd August Defra confirmed an outbreak of foot and mouth disease on a farm near Guildford in Surrey. Defra confirmed that the FMDV strain found in Surrey is most similar to strains used in international diagnostic laboratories and in vaccine production, including at the Pirbright site shared by the Institute of Animal Health (IAH) and Merial Animal Health Ltd, a pharmaceutical company. The present indications are that this strain is an O1 BFS67-like virus, isolated in the 1967 Foot and Mouth Disease outbreak in Great Britain. This strain is present at the IAH and was used in a batch manufactured in July 2007 by the Merial facility. On a precautionary basis Merial has agreed to voluntarily halt vaccine production. Defra confirms a second case of foot and mouth on a farm within the 3km protection zone. Between 50 and 100 cows on the affected farm have been culled. As expected, the Health and Safety Executive’s initial report concludes that “there is a strong probability that the FMDV strain involved in the farm outbreak originated from the IAH or the Merial sites”. The letter to the Minister says “There is no reason to prevent the Institute for Animal Health from operating providing that all the usual biosecurity protocols are followed rigorously” but that “The situation regarding Merial is less clear cut, and I would advise that further work be done before any operations involving live pathogens are restarted. As the report indicates there are doubts about the integrity of the drainage system, including pipe work which leads to the final effluent treatment plant”. The report also says “Release by human movement must also be considered a real possibility. Further investigation of the above issues is required and is being urgently pursued”. Chief veterinary officer Debby Reynolds told a news conference she had ordered livestock on a third farm in Surrey to be culled on suspicion the disease may have spread.

Defra: Interactive map

10 Facts About Foot and Mouth Disease:

1. Foot-and-mouth disease (FMD) is a highly infectious disease of hoofed animals (ungulates) such as cattle, sheep, goats and pigs. It can also infect elephants, rats, and hedgehogs.
2. The symptoms of FMD are fever followed by the development of vesicles (blisters) chiefly in the mouth and on the feet.
3. Affected animals suffer weight loss from which they do not recover for several months, and in cows milk production can decline significantly. Although most animals eventually recover from FMD the disease can be fatal, especially in newborn animals.
4. Foot and mouth disease is caused by a Picornavirus.
5. FMD has an incubation period of 2-14 days before symptoms appear. The virus can survive in dry faecal material for 14 days in summer, in slurry for six months in winter, in urine for 39 days and on the soil for up to 28 days.
6. Some infected animals remain asymptomatic carriers of FMD which can transmit the disease to other animals.
7. The last major outbreak of foot and mouth disease in the UK in 2001 led to the slaughter of between 6.5 to 10 million animals and is estimated to have cost the country up to £8.5 billion.
8. The United States, Canada, Australia, Japan, Indonesia and Korea are currently free of FMD, but the disease is present in Eastern Europe, Asia, Africa and South America.
9. Vaccination against FMD is difficult because there are seven serotypes of the virus and a vaccine for one serotype does not protect against any others. Vaccination only provides temporary immunity. Defra Decision Tree for Disease Control Strategies against FMD
10. Humans can be infected with foot-and-mouth disease through close contact with infected animals, but this is extremely rare and human infections are not fatal. Because the virus that causes FMD is sensitive to stomach acid, it cannot spread to humans via consumption of infected meat or milk.