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Identification of neutralizing antigenic sites on VP1 and VP2 of type A5 foot-and-mouth disease virus, defined by neutralization-resistant variants.

Five neutralizing monoclonal antibodies (nMAbs) obtained against type A5 Spain-86 foot-and-mouth disease virus were used to generate a series of neutralization-resistant variants. In vitro and in vivo assays showed that the variants were fully refractory to neutralization by the selecting nMAb. On the basis of cross-neutralization and binding assays, two neutralizing antigenic sites have been located on the virus surface; one, located near the C-terminus of VP1, displayed a linear epitope, and the second, located on VP2, displayed two conformational epitopes. Nucleotide sequencing of RNA of the parental and variant capsid protein-coding region P1 has placed the amino acid changes at position 198 of VP1 for the first site and at positions 72 and 79 of VP2 for the related epitopes in the second site. The relative importance of these two sites in the biological properties of foot-and-mouth disease virus is discussed.

Amino Acid Sequence↗

[Testing area Wehl: study of risks of contacts in behalf of foot-and-mouth disease].

A study on contacts between livestock holdings was conducted in a geographically defined area of 4 by 6 km in the Netherlands. The farmers were asked to record all contact on and off farm during a period of 2 weeks. The number of contacts in the 2 week period was high, on average 91.8 contacts per farm. The risk of spreading foot-and-mouth disease on or off the farm was greater for cattle farms than for swine farms. Relatively more people had contact with the animals while visiting cattle farms, thereby causing the higher risk. Most contacts occurred over short distances. Almost 50% of the contacts were within the research area. This finding confirms the importance of restricted areas around farms with foot-and-mouth disease infections.

Animal Husbandry↗

The duration of the foot-and-mouth disease virus carrier state in African buffalo (i) in the individual animal and (ii) in a free-living herd.

The maintenance of a virus depends on a number of factors, including the duration of infectivity and the size of the available host population. In this work, foot-and-mouth disease virus was shown to persist in individual African buffalo (Syncerus caffer) for up to at least five years; thus, the duration of infectivity is more than adequate to cover the normal periods between calving peaks. In a small isolated free-living population which varied from 30 to 100 buffalo, two immunological types of foot-and-mouth disease virus were maintained for at least 24 years and through several generations.

Animals↗

[Expression of foot and mouth disease virus antigens in transgenic plants].

Owing to its geographical distribution and its highly contagious character, the foot and mouth disease (FMD) virus is responsible for one of the most dreaded of all livestock diseases. The currently-used vaccine is polyvalent and is based on an inactivated virus. Current research on FMD vaccines focuses on the creation of vaccines that are easier and cheaper to produce, and that avoid manipulation of large quantities of virus. The use of transgenic plants to express relevant antigens has been evaluated for the purpose of vaccine production. The authors' working group has taken the FMD virus as a model to evaluate the feasibility of using transgenic plants to express viral antigens and to develop experimental vaccines. The purpose of this paper is to set forth the working group's results in the expression of FMD antigens in transgenic plants.

Animals↗

[Hand, foot and mouth disease. Report of 10 cases].

Ten children with hand-foot-and-mouth disease are described and their clinical manifestations reported in detail. It is a benign, minor viral disease of childhood, but in our country its real incidence is unknown. Diagnosis in the clinical practice is based on the recognition of typical and atypical localizations of the vesicular eruption, as well as on the identification of extracutaneous and extrabuccal manifestations. The differential diagnosis includes herpangina, aphthous stomatitis, dyshidrosis and erythema multiforme.

Child↗

Identification of foot and mouth disease virus carrier and subclinically infected animals and differentiation from vaccinated animals.

Countries that are free of foot and mouth disease (FMD) are reluctant to use vaccine in the event of an outbreak because of the difficulties this can cause in re-establishing freedom from FMD status to the satisfaction of trading partners. The problem does not lie in distinguishing between vaccinated and recovered animals as vaccinated animals can be tagged or otherwise marked to show that they have been vaccinated; the difficulty is in identifying vaccinated animals that have had contact with live virus and become carriers. The traditional probang test is not sufficiently sensitive and is labour- and laboratory-intensive, but alternative serological tests such as those for antibodies to non-structural proteins (NSPs), or specific immunoglobulin A (IgA) are also not 100% sensitive. However, these newer tests do provide increased security by reducing the likelihood of trading carrier animals and can be used to help define the limits of an outbreak; the use of vaccine to help control an outbreak of FMD in a previously free country still has significant consequences on trade in FMD susceptible animals and their products.

Animals↗

Molecular epidemiology of the foot-and-mouth disease virus outbreak in the United Kingdom in 2001.

The objective of this study was to quantify the extent to which the genetic diversity of foot-and-mouth disease virus (FMDV) arising over the course of infection of an individual animal becomes fixed, is transmitted to other animals, and thereby accumulates over the course of an outbreak. Complete consensus sequences of 23 genomes (each of 8,200 nucleotides) of FMDV were recovered directly from epithelium tissue acquired from 21 farms infected over a nearly 7-month period during the 2001 FMDV outbreak in the United Kingdom. An analysis of these consensus sequences revealed very few apparently ambiguous sites but clear evidence of 197 nucleotide substitutions at 191 different sites. We estimated the rate of nucleotide substitution to be 2.26 x 10(-5) per site per day (95% confidence interval [CI], 1.75 x 10(-5) to 2.80 x 10(-5)) and nucleotide substitutions to accrue in the consensus sequence at an average rate of 1.5 substitutions per farm infection. This is a sufficiently high rate showing that detailed histories of the transmission pathways can be reliably reconstructed. Coalescent methods indicated that the date at which FMDV first infected livestock in the United Kingdom was 7 February 2001 (95% CI, 20 January to 19 February 2001), which was identical to estimates obtained on the basis of purely clinical evidence. Nucleotide changes appeared to have occurred evenly across the genome, and within the open reading frame, the ratio of nonsynonymous-to-synonymous change was 0.09. The ability to recover particular transmission pathways of acutely acting RNA pathogens from genetic data will help resolve uncertainties about how virus is spread and could help in the control of future epidemics.

Animals↗

Investigation of the possible spread of foot-and-mouth disease virus by the burning of animal carcases on open pyres.

An atmospheric dispersion model was used to predict the airborne spread and concentrations of foot-and-mouth disease virus within the plumes generated by 11 pyres built to burn infected carcases during the epidemic of 2001 in the UK. On the basis of assumptions about the quantity of virus emitted during the three hours after the pyres were built and the threshold concentration of virus required to cause an infection in cattle, it was concluded that none of the disease breakdowns which occurred under the plumes was due to the spread of virus from the pyres.

Air Microbiology↗

Identification of novel foot-and-mouth disease virus specific T-cell epitopes in c/c and d/d haplotype miniature swine.

To identify foot-and-mouth disease virus (FMDV) specific T-cell epitopes within the non-structural protein 3D in swine, pentadecapeptides were tested in proliferation and Interferon-gamma ELISPOT assays using lymphocytes from two strains of inbred miniature pigs (c/c and d/d haplotype) experimentally infected with FMDV. Lymphocytes of c/c pigs recognized peptides from three different regions in 3D, d/d lymphocytes recognized peptides from two regions, one of them being adjacent to an epitope of c/c pigs and comprising amino acid residues 346-370. Analyses of the response of d/d lymphocytes against peptides representing the structural protein 1A revealed another novel T-cell epitope. Investigation of the phenotype of responding lymphocytes showed a response of CD4(+)CD8(+)MHC-class-II(+) cells, identifying them as activated T-helper cells. This is the first report on FMDV specific T-cell epitopes recognized by swine leukocyte antigen (SLA) inbred swine and provides information useful for the design of novel vaccines against FMDV.

Amino Acid Sequence↗

[Construction and identification of recombinant adenovirus containing the polyproteins coding regions of O type foot-and-mouth disease virus by homologous recombination in Escherichia coli].

The gene coding for the polyprotein (PP) of foot-and-mouth disease virus (FMDV)was obtained by PCR from recombinant plasmid rpMD18-T/PP. The PCR product was digested with Xba I and Not I and inserted into the cloning site of the adenovirus shuttle vector pAdTrack-CMV, previously digested with the same enzymes. This recombinant shuttle plasmid was designated rpAd-CMV/PP. The recombinant adenovirus vector rpAd/PP was obtained by homologous recombination of plasmid rpAd-CMV/PP and adenovirus skeletal vector pAdeasy-1 in E. coli. Plasmid rpAd/PP was linearized by Pme I and transformed into 293 competent cells to pack the adenovirus using liposome mediated gene transfer method and, as a result, the recombinant adenovirus rAd/PP that contained the polyprotein coding gene was obtained. Obvious CPE could be observed under an inverted microscope, the green fluorescence protein expression can be detected under fluorescence microscope and the empty capsid of FMDV was observed under electron microscope. These results indicated that the recombinant adenovirus rAd/PP expressed the PP protein and that this protein could be assembled into the empty capsid of FMDV. The recombinant adenovirus obtained in this study can be used for further research for making FMDV recombinant adenovirus vaccine.

Adenoviridae↗

Vaccination as a means of control of foot-and-mouth disease in sub-saharan Africa.

The presence of foot-and-mouth disease (FMD) in a country is a major obstacle to the development of agriculture because of its adverse effects on livestock production and agricultural exports. The eradication of FMD in sub-saharan Africa by the implementation of slaughtering-out is impractical for various reasons, but vaccination with good quality FMD vaccines can help prevent losses in stock production and reduce the overall incidence of the disease. Oil based FMD vaccines have been used with success in South American countries and have logistic and immunological advantages which would make them useful in sub-saharan African countries. The wide intratypic variation of SAT strains prevalent in sub-saharan Africa and their endemicity in African buffalo, presents a challenge to vaccine producers and requires constant epidemiological surveillance to ensure the relevance of vaccines to field conditions.

Africa South of the Sahara↗

[Isolation of bovine cell lines and susceptibility to foot-and-mouth disease virus].

Morphology and chromosomes of cell sublines derived from two new bovine kidney lines are reported. Cell susceptibility to the foot-and-mouth disease virus is discussed. One of the sublines showed epithelial-like cells, while the remainder, elonged fibroblastic-like cells. Most of them had a diploid number of chromosomes. From these sublines only one was sensible to the foot-and-mouth disease virus.

Animals↗

History of the control of foot and mouth disease.

From the many existing documents on the history of foot and mouth disease, it is possible to describe the practical measures adopted for disease surveillance and control from ancient times until the 20th century. Surveillance was based on diagnosis or post-mortem examination, and also on knowledge of the conditions under which infection occurred: aetiology, pathogenesis, mode of infection, susceptible species, virulent material, etc. The historical facts are assembled and compared, with comments on each of these points. Control was based upon the application of isolation, then slaughter or aphtisation, then vaccination. A study of these various procedures makes it possible to compare their efficacy.

Animals↗

Effect of zinc and other chemical agents on foot-and-mouth-disease virus replication.

Chemical agents reported to inhibit the growth of various ribonucleic acid and deoxyribonucleic acid viruses were tested against foot-and-mouth disease virus in cell culture. These included Zn(2+), aurintricarboxylic acid, polyribocytidylic acid, polyriboinosinic acid, phosphonoacetic acid, and the viral contact inactivator N-methyl isatin beta-thiosemicarbazone alone and with CuSO(4). The most effective agent, Zn(2+), inhibited foot-and-mouth disease virus production in primary calf kidney cells by 1 log unit at 0.05 mM Zn(2+) and completely at 0.50 mM. Zinc was inhibitory even when added late in infection and was nontoxic to uninfected cells as measured by protein and nucleic acid syntheses. Polyacrylamide gel patterns of [(35)S]methionine-labeled, virus-specific proteins showed increasing amounts of higher-molecular-weight material, in accord with reports that Zn(2+) inhibits post-translational cleavages of other picornavirus precursor polypeptides.

Antiviral Agents↗

Epidemiological study of an "hand-foot-and-mouth disease" outbreak observed in Rome in the fall of 1973.

An outbreak of "hand-foot-and-mouth disease" (HFMD) occurred in Nov. 1973 in a nursery school. Sixty-seven children were studied, 15 of whom presented clinical signs of the disease. Sixty-two percent of the HFMD cases and 18% of asymptomatics were proved to be infected with Coxsackie virus A 16. The ratio of clinical to asymptomatic infection of nursery-school children with confirmed Coxsackie A 16 infection was 58%. The accidental diffusion of the infection led to the occurrence of secondary cases. This allowed to establish the incubation period of the illness at 8 to 12 days, for 3 individual cases where a single infecting contact in a very definite time could be documented. Fecal excretion of virus was demonstrable in 2 cases up to 10-20 days, while the duration of oral excretion appeared to be somewhat shorter. Evidence was also obtained showing that infectious virus could be spread by patients during the incubation period. Virus isolations were more easily obtained in suckling mice than in cell culture.

Adult↗

Experiments on the preparations and testing of associated vaccine against foot and mouth disease and vesicular disease in swine.

Tests for associated immunization of swine against Foot and Mouth Disease (FMD) and Vesicular Disease (SVD) of swine were carried out. As a result of this investigation, it was established that the prepared and tested inactivated oil vaccine is harmless and immunogenic in sensitive animals. In investigating the course of immunity, the presence of antibody against both antigens was demonstrated in vaccinated animals. All once-vaccinated animals were defended against the virus of SVD during challenge, and 75% of them were defended against FMD. After revaccination, all immunized swine were defended against infection with both viruses. The question of the quality of the associated vaccine and the possibilities of its massive use in industrial swine rearing was discussed.

Adjuvants, Immunologic↗