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PubMed1984

Multiple proteases in foot-and-mouth disease virus replication.

Translation of foot-and-mouth disease virus RNA in a rabbit reticulocyte lysate for short time intervals resulted in the production of the peptides P20a , P16, and P88 (Lab, Lb, and P1) (R. R. Rueckert , Recommendations of the 3rd European Study Group on Molecular Biology of Picornavirus, Urbino , Italy, 1983). If further translation was prevented, the structural protein precursor P88 was not cleaved, even after prolonged incubation. This result indicates that the mechanism of the cleavage between P20a -P16 and P88 and of that between P88 and P52 (P2) differs from the mechanism of the secondary cleavages which produce the structural proteins. Furthermore, treatment of foot-and-mouth disease virus-infected cells with the protease inhibitor D-valyl phenylalanyl lysyl chloromethyl ketone prevented the in vivo cleavage between P20a -P16 and P88 but had no effect on any of the other cleavage events. These results suggest that the cleavage of the foot-and-mouth disease virus polyprotein utilizes two different host proteases.

Animals↗
PubMed2001

Eradication of foot and mouth disease in Japan.

An outbreak of foot and mouth disease (FMD) was recorded in Japan in the spring of 2000, the first for ninety-two years. Between 25 March and 11 May, four farms were infected. However, the disease was eradicated without resorting to vaccination, through a campaign of culling, movement control of cloven-hoofed animals in areas surrounding infected premises, and intensive clinical and serological surveillance. Japan regained FMD-free status by the end of September 2000. The authors describe the nature of the outbreaks, the eradication measures implemented, and the clinical and serological surveillance methods used. The possible sources of infection are also examined. Finally, the direct and indirect economic losses are presented.

Animals↗
PubMed2006

Use and abuse of mathematical models: an illustration from the 2001 foot and mouth disease epidemic in the United Kingdom.

Foot and mouth disease (FMD) is a major threat, not only to countries whose economies rely on agricultural exports, but also to industrialised countries that maintain a healthy domestic livestock industry by eliminating major infectious diseases from their livestock populations. Traditional methods of controlling diseases such as FMD require the rapid detection and slaughter of infected animals, and any susceptible animals with which they may have been in contact, either directly or indirectly. During the 2001 epidemic of FMD in the United Kingdom (UK), this approach was supplemented by a culling policy driven by unvalidated predictive models. The epidemic and its control resulted in the death of approximately ten million animals, public disgust with the magnitude of the slaughter, and political resolve to adopt alternative options, notably including vaccination, to control any future epidemics. The UK experience provides a salutary warning of how models can be abused in the interests of scientific opportunism.

Animal Welfare↗
PubMed2002

Control of foot and mouth disease: the experience of the Americas.

Foot and mouth disease (FMD) was first recognised in South America in 1870, almost simultaneously in the province of Buenos Aires (Argentina), in the central region of Chile, in Uruguay, in southern Brazil and coincidentally, on the northeastern coast of the United States of America. The epidemiology of the disease was unknown and no government action was taken following the initial outbreaks. This resulted in the disease spreading to other areas of Chile, as well as to Peru, Bolivia and Paraguay, reaching Venezuela and Colombia in the 1950s, and Ecuador in 1961. The entire continent was affected in the 1960s when national FMD control programmes were initiated, with the exception of Guyana, Surinam, French Guiana and Patagonia. In the 1970s, steps were taken to implement a regional control and eradication strategy in view of the impact of production and trade on the persistence of the virus. The Plan Hemisférico de Erradicación de la Fiebre Aftosa (PHEFA: Hemispheric FMD Eradication Plan), public- and private-sector policies, new diagnostic tools, the oil-adjuvanted FMD vaccine and regional strategies played a part in improving the epidemiological situation during the 1990s. A setback was encountered in 2000 and 2001, with outbreaks due to virus types A and 0 recorded in Argentina, Uruguay and Brazil.

Animals↗
PubMed2003

Role of nonstructural proteins 3A and 3B in host range and pathogenicity of foot-and-mouth disease virus.

The genome of foot-and-mouth disease virus (FMDV) differs from that of other picornaviruses in that it encodes a larger 3A protein (>50% longer than poliovirus 3A), as well as three copies of protein 3B (also known as VPg). Previous studies have shown that a deletion of amino acids 93 to 102 of the 153-codon 3A protein is associated with an inability of a Taiwanese strain of FMDV (O/TAW/97) to cause disease in bovines. Recently, an Asian virus with a second 3A deletion (amino acids 133 to 143) has also been detected (N. J. Knowles et al., J. Virol. 75:1551-1556, 2001). Genetically engineered viruses harboring the amino acids 93 to 102 or 133 to 143 grew well in porcine cells but replicated poorly in bovine cells, whereas a genetically engineered derivative of the O/TAW/97 virus expressing a full-length 3A (strain A12) grew well in both cell types. Interestingly, a virus with a deletion spanning amino acid 93 to 144 also grew well in porcine cells and caused disease in swine. Further, genetically engineered viruses containing only a single copy of VPg were readily recovered with the full-length 3A, the deleted 3A (amino acids 93 to 102), or the "super" deleted forms of 3A (missing amino acids 93 to 144). All of the single-VPg viruses were attenuated in porcine cells and replicated poorly in bovine cells. The single-VPg viruses produced a mild disease in swine, indicating that the VPg copy number is an important determinant of host range and virulence. The association of VPg copy number with increased virulence in vivo may help to explain why all naturally occurring FMDVs have retained three copies of VPg.

Animals↗
PubMed2003

Novel viral disease control strategy: adenovirus expressing alpha interferon rapidly protects swine from foot-and-mouth disease.

We have previously shown that replication of foot-and-mouth disease virus (FMDV) is highly sensitive to alpha/beta interferon (IFN-alpha/beta). In the present study, we constructed recombinant, replication-defective human adenovirus type 5 vectors containing either porcine IFN-alpha or IFN-beta (Ad5-pIFNalpha or Ad5-pIFNbeta). We demonstrated that cells infected with these viruses express high levels of biologically active IFN. Swine inoculated with 10(9) PFU of a control Ad5 virus lacking the IFN gene and challenged 24 h later with FMDV developed typical signs of foot-and-mouth disease (FMD), including fever, vesicular lesions, and viremia. In contrast, swine inoculated with 10(9) PFU of Ad5-pIFNalpha were completely protected when challenged 24 h later with FMDV. These animals showed no clinical signs of FMD and no viremia and did not develop antibodies against viral nonstructural proteins, suggesting that complete protection from infection was achieved.

Adenoviridae↗
PubMed2002

Epidemiological basis useful for the control of foot-and-mouth disease.

Although known for many years, foot-and-mouth disease is still able to represent a real threat to many farming economies in the world. The recent 2001 Western European epizootics linked to O PanAsia virus strain can illustrate the fact that many questions are still unanswered in the field of foot-and-mouth epidemiology. It also demonstrates that the increase in international trade, including livestock, animal products and animal food, means an increase in the probability of transmitting, through the same way, some animal diseases, foot-and-mouth included. In our economies, a rapid identification of the virus and a fast elimination of infected, contaminated and even some contact animals are still the key factors to react in front of such a disease.

Animal Husbandry↗
PubMed2001

[Vaccination against foot and mouth disease: current state and perspectives].

Foot-and-mouth disease (FMD) is endemic in many parts of the world and poses a permanent threat for cloven-hoofed animals in all countries. The available vaccines against FMD are safe and efficacious. Combat of FMD by vaccination is controversial in currently FMD-free countries including the ones of the European Union. The article summarizes our knowledge concerning production and use of vaccines, virus persistence, differentiation between vaccinated and infected animals, vaccination programs and perspectives of vaccine development.

Animals↗
PubMed2005

Linear hoof defects in sheep infected with foot-and-mouth disease.

During the epidemic of foot-and-mouth disease (FMD) in The Netherlands in 2001, a sheep farm was identified that had been subclinically infected with the disease. The FMD virus genome was detected in 12 of 16 probang samples collected from the sheep and the virus was isolated from four of these samples. Linear defects were observed, 1 to 3 cm from the coronary band, in the hooves of several of the sheep. The defects were thought to have been caused by the FMD infection. It was thought that the distance of the defects from the coronary band might be an indication of the time since the animals had been infected. To determine the growth rate of the claws of sheep, the growth of the hoof horn of uninfected lambs and ewes was measured; in the lambs the growth rate was 0.44 mm per day and in the ewes it was 0.29 mm per day.

Animals↗
PubMed2006

Selective lymphocyte depletion during the early stage of the immune response to foot-and-mouth disease virus infection in swine.

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious vesicular disease of cloven-hoofed animals. In the present study we use FMDV serotype C infection of swine to determine, by analytical techniques, the direct ex vivo visualization of virus-infected immune cells during the first 17 days of infection. We report, for the first time, that FMDV C-S8c1 can infect T and B cells at short periods of time postinoculation, corresponding with the peak of the viremia. There is a significant lymphopenia that involves CD3(+) CD4(-) CD8(+/-), CD3(+) CD4(-) CD8(+)Tc, and CD3(+) CD4(+) CD8(+) memory Th but not CD3(+) CD4(+) CD8(-) naïve Th lymphocytes. In addition, a profound depletion of the vast majority of peripheral T cells in lymph nodes and spleen is observed. This selective depletion of T cells is not due mainly to in situ death via apoptosis as visualized by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique. Thus, early infection of T cells by FMDV may be the main cause of the observed T-cell depletion. Importantly, this lack of T cells is reflected in a reduced response to mitogen activation, which in many cases is totally eliminated. These data suggest a mechanism by which the virus causes a transient immunosuppression, subvert the immune systems, and spreads. These results have important implications for our understanding of early events in the development of a robust immune response against FMDV.

Animals↗
PubMed2002

Global perspective for foot and mouth disease control.

The world distribution of foot and mouth disease (FMD) is almost a mirror image of the global economic structure. In general, industrialised countries are free while the disease is endemic in developing countries. In recent years, several incursions of FMD have been recorded in countries belonging to the Organization for Economic Co-operation and Development (OECD), all of which have been financially and socially costly to eliminate. At the same time, this single disease bars many developing countries from participation in formal trade, both regionally and internationally. However, recent studies have predicted an unprecedented high demand for animal protein, which can only be met through enhanced participation of developing countries in trade in livestock products. Accordingly, globalisation trends will exacerbate the exclusion of poor communities and countries from markets unless a long-term strategy is implemented to progressively build market opportunities for these countries, without placing the livestock of industrialised countries at undue risk from FMD and other major transboundary animal diseases. The authors submit that there is sufficient knowledge of FMD to make an international initiative for the progressive control of FMD a viable objective. Consequently, a four-stage pathway is proposed for developing a global FMD programme. The proposed strategy involves a build-up of the epidemiology and global status of FMD, including establishing an international early warning system, a risk-reduction phase to lower the incidence of FMD in the primary endemic areas and a control phase leading to the creation of zones of assured FMD-freedom. The authors also propose that an international FMD programme be co-ordinated, based on the experience of the Global Rinderpest Eradication Programme, the Hemispheric Plan for the eradication of FMD for the Americas, the South-East Asia Foot and Mouth Disease control and eradication campaign and the European Commission for the Control of FMD.

Animals↗
PubMed2005

A survey to investigate movements off sheep and cattle farms in New Zealand, with reference to the potential transmission of foot-and-mouth disease.

AIM: To quantify the numbers and extent of movements off sheep and cattle farms in New Zealand, in order to construct more realistic simulation models to investigate how infectious diseases such as foot-and-mouth disease (FMD) might spread. METHODS: Farmers from 500 randomly selected farms, comprising 100 from each of the following sectors, viz beef, dairy, grazing/dairy heifer rearing, sheep, and mixed sheep and beef, were asked to fill in diaries in which they recorded the movements of all animals, products, people, vehicles and equipment coming on to or leaving their farms during two separate 3-week periods, representing relatively 'busy' and 'quiet' times of the year with respect to livestock movements. Where possible, the destination of each movement was identified and geo-coded, to allow the distance travelled to be calculated. Each movement was then classified according to the risk of transfer of FMD virus (FMDV), should the disease have been present on the study farm at the time of the movement. The data were then analysed to establish movement frequencies and distributions of distances travelled, by the different pastoral livestock sectors. RESULTS: Two hundred and seventeen farmers returned one or more diaries. One hundred and ninety-three farmers completed a Busy-period diary, recording a total of 12,052 movements off their farms, a crude average of 62.4 per 3-week period, or 2.97 per day. Of these, 4.0% involved the transport of livestock, equating to 0.12 livestock consignments per day. In contrast, 186 Quiet-period diaries were returned, recording a total of 10,885 movements off, representing a crude average of 58.5 during the 3-week period, or 2.78 per day. Of these, 2.1% involved livestock, equating to 0.06 livestock consignments per day. The mean and median distances travelled during the Busy periods were 30.9 km and 13.1 km, respectively (range 0-1,167 km). In comparison, the mean and median distances travelled during Quiet periods were 41.3 and 14 km, respectively (range 0.4-1,203 km). CONCLUSIONS: People, vehicles, livestock and other items can travel off pastoral livestock farms in New Zealand to other farms either directly or via saleyards over extensive distances. This has implications for the potential spread of infectious diseases such as FMD. Movement parameters intended for use in the InterSpread Plus inter-farm simulation model of FMD were established, which will facilitate the prediction of likely spread and efficacy of controls in the unlikely event of a real-life outbreak.

Animals↗
PubMed1988

[Antigenic structure of the foot-and-mouth disease virus. II. Synthesis of protective peptides from the major immunogenic region of VP1 protein of foot-and-mouth disease virus type A22].

Earlier we found that the immune response and antiviral protection from FMDV can be achieved by immunization with uncoupled FMDV peptides. In a search of approaches to animal protection from FMDV A22 strain we prepared a series of peptides corresponding to the putative antigenic determinants. Synthetic 131-149 and 140-149 sequences afforded 50 to 80% protection, both in the free state and conjugated with keyhole limpet hemocyanin. We believe that the 140-149 segment is so far the smallest peptide capable of eliciting specific antiviral protection without conjugation with a high molecular carrier.

Animals↗