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A porcine CD8+ T cell clone with heterotypic specificity for foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV)-specific T cell lines and clones have been obtained from a swine lymphocyte antigen (SLA) inbred miniature pig vaccinated with chemically inactivated virus. One of the clones obtained, CE3, showed a specific and heterotypic proliferation against infectious but not inactivated FMDV in the presence of syngeneic peripheral blood mononuclear cells (PBMC). Adherent cells from PBMC were sufficient to support specific activation of the clone and the proliferation was abolished when the contact between CE3 and adherent cells was prevented. Phenotypic characterization of CE3 cells revealed expression of CD2, CD25 (interleukin-2 receptor), SLA class I and SLA class II. Furthermore, the cells were highly CD8 positive but showed low expression of CD4. The expression of T cell receptor (TCR) alpha and beta genes confirmed their T cell nature. Consistent with the CD8 phenotype, the proliferative response of CE3 was inhibited with MAbs to SLA class I and CD8. Altogether, these results indicate that CE3 is a porcine SLA class I-restricted CD8+ T cell clone, that recognizes a heterotypic FMDV antigen.

Animals↗

In vitro morphogenesis of foot-and-mouth disease virus.

Foot-and-mouth disease virion RNA is translated efficiently and completely in a rabbit reticulocyte lysate cell-free system. Treatment of cell-free lysates with monospecific serum prepared against the individual viral structural proteins or with monoclonal antibodies prepared against the inactivated virus or against a viral structural protein precipitated all of the structural proteins, suggesting that structural protein complexes were formed in vitro. Sucrose gradient analysis of the cell-free lysate indicated that complexes sedimenting at 5, 14, 60 to 70, and ca. 110S were assembled in vitro. Structural proteins VP0, VP1, and VP3 were the major polypeptides found in these complexes. The material sedimenting at 110S, i.e., containing VP0, VP1, and VP3, was precipitated by a 140S-specific monoclonal antibody but not by a 12S subunit-specific monoclonal antibody, suggesting that this capsid structure contained at least one epitope present on the intact virus.

Animals↗

A second protease of foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV) genes are expressed as a polyprotein which is rapidly processed into the four primary cleavage products L, P1, P2, and P3. In secondary cleavage reactions, these are further processed into the mature proteins. The FMDV L protein is located at the N terminus of the polyprotein and is the first gene product released from the nascent polyprotein. For analysis of its biological function, the L gene was mutated by site-directed mutagenesis of cloned cDNA. In vitro translation of in vitro transcripts of these DNAs and expression studies in Escherichia coli showed that the L mutants affect the processing of the viral polyprotein. The mutants isolated were partially or totally defective in processing the polyprotein at the L/P1 junction. These mutants could, however, be processed in the presence of the wild-type L protein. Furthermore, an antiserum directed against the L protein inhibited processing at the L/P1 cleavage site, so that the release of the L protein from the polyprotein was blocked. These data reveal that the L gene product represents a viral protease which catalyzes its own release from the nascent polyprotein.

Animals↗

Clinical variation in foot and mouth disease: sheep and goats.

Foot and mouth disease (FMD) in adult sheep and goats is frequently mild or unapparent, but can cause high mortality in young animals. The recent outbreak of FMD in the United Kingdom has highlighted the importance of sheep in the epidemiology of the disease, although there have been numerous examples in the past where small ruminants have been responsible for the introduction of FMD into previously disease-free countries. The difficulty in making a clinical diagnosis should encourage the development of more rapid screening tests to assist in future control programmes.

Animals↗

Re-assessing the likelihood of airborne spread of foot-and-mouth disease at the start of the 1967-1968 UK foot-and-mouth disease epidemic.

The likelihood of airborne spread of foot-and-mouth disease at the start of the 1967-1968 epidemic is re-assessed in the light of current understanding of airborne disease spread. The findings strongly confirm those made at the time that airborne virus was the most likely cause of the rapid early development of the disease out to 60 km from the source. This conclusion is reached following a detailed epidemiological, meteorological and modelling study using original records and current modelling techniques. The role played by 'lee waves' as the mechanism for the spread is investigated. It is thought that they played little part in influencing the development of the epidemic. A number of lessons learned from the work are drawn, identifying the need for further research on the quantity and characteristics of airborne virus. The results are also used to illustrate what advice would have been available to disease controllers if the outbreak had occurred in 2004.

Air Microbiology↗

Predicting the spread of foot and mouth disease by airborne virus.

Foot and mouth disease (FMD) can spread by a variety of mechanisms which, under certain climatic and epidemiological conditions, includes the windborne spread of disease. Recent advances in knowledge of the aerobiological features of FMD are described. The strain of virus and species of infected animal are major determinants of airborne virus emission. Pigs emit most virus, cattle and sheep lesser but similar amounts to each other. Peak excretion of airborne virus by sheep occurs before the clinical phase of disease, whereas with cattle and pigs, it coincides with the development of early clinical disease. The probability of aerogenous infection differs greatly between livestock species. Cattle are the most susceptible, followed by sheep, whereas pigs are very resistant. Computer-based simulation models have been developed to analyse and predict the risk of airborne spread of FMD and have been used successfully during outbreaks to support decision-making. Further research is required to refine and extend the models for operational use.

Aerosols↗

Use of the reverse transcription polymerase chain reaction (RT-PCR) for the rapid diagnosis of foot and mouth disease in South America.

Foot and mouth disease (FMD) is a limiting factor for the economic progress of the animal industry in South America. The presence of the disease results in the imposition of national and international sanitary barriers to animals and animal products, and, most especially, a reduction in the availability of protein from animal origin and in income. Rapid and accurate identification of infected animals, those with either clinical or subclinical disease as well as with persistent infection, is essential for maintaining an efficient eradication programme. The polymerase chain reaction was used to rapidly identify infected animals. With a primer set that corresponds to a conserved region of the 3D sequence of the viral genome, it was possible to amplify, regardless of the serotype, 116 strains of FMD virus, of which 109 were strains collected from outbreaks of FMD throughout South America from 1945 to the most recent outbreaks in 2000/2001. The PCR technique should be of considerable value in facilitating the diagnosis of FMD in South America. where laboratory resources are limited and a rapid response is needed, particularly in areas where national programmes for controlling or eradicating the disease are being implemented.

Animals↗

Dose-dependent responses of sheep inoculated intranasally with a type O foot-and-mouth disease virus.

Unlike foot-and-mouth disease (FMD) in cattle and pigs, which spreads rapidly, resulting in easily detectable foci of clinical infection, the disease in sheep is characterized by restricted transmission, low morbidity and sporadic clinical cases. The study described was designed to investigate whether the ability of sheep to transmit and maintain FMD virus was dose-related. The viral isolate used was known to be associated epidemiologically with rapid fade-out of transmission within sheep flocks. Five separate transmission experiments were performed, with different doses of FMD virus, each experiment containing five intranasally inoculated donor sheep and 10 in-contact recipient sheep. The lowest dose required to cause clinical infection by inoculation (10(4) 50% tissue culture infectious doses; 10(4) TCID50) was also the optimum dose for producing in-contact transmission. Inoculation of donor sheep with higher doses (10(5) and 10(6) TCID50) resulted in reduced transmission, characterized by reduced duration and degree of viraemia and an early humoral and cell-mediated immune response. Principal component analysis was used to interpret the complex interactions of the dose-related responses to infection.

Administration, Intranasal↗

[An epidemic of hand, foot and mouth disease].

Five patients with hand-, foot- and mouth disease, caused by infection with Coxsackievirus type A16, are described in an epidemic outbreak of this disease. Hand-, foot- and mouth disease, is characterized by a most distinctive enanthem-exanthemcomplex. In 65% of the cases a vesiculopapular exanthem is noted. Most cases are described in epidemic outbreaks. Although the vast majority of occurrences of the disease have been due to Coxsackie A16 viral infections, occasionally Coxsackie A5, A10 and enterovirus 71, seldom Coxsackievirus B1 or B3, have been etiologically incriminated. In this article attention is paid to the clinical characteristics, the epidemiology and the differential diagnostic aspects of hand-, foot- and mouth disease.

Child, Preschool↗

Development of a rapid chromatographic strip test for the pen-side detection of foot-and-mouth disease virus antigen.

Foot-and-mouth disease (FMD) is the most contagious animal virus disease of cloven-hoofed livestock and requires reliable and accurate diagnosis for the implementation of measures to control effectively its spread. Routine diagnosis of FMD is carried out at the OIE/FAO World Reference Laboratory for Foot-and-Mouth Disease (WRL for FMD), Pirbright by the combined use of ELISA and virus isolation in cell culture supplemented by reverse transcription polymerase chain reaction (RT-PCR) methods. These techniques require skilled personnel and dedicated laboratory facilities which are expensive. The development of a rapid and simple test for the detection of FMD virus antigen using Clearview chromatographic strip test technology for field application is described. This device detected FMD viral antigen in nasal swabs, epithelial suspensions and probangs from clinical samples submitted from the field, from animals infected experimentally and in supernatant fluids resulting from their passage in cell culture. The test system was more sensitive than ELISA for the diagnosis of all seven serotypes of FMD virus in the epithelial suspensions and nasal swabs and had equivalent sensitivity to the ELISA for the detection of contemporary virus strains in cell culture supernatant fluids. The study demonstrated the potential for this device to confirm a clinical diagnosis at the site of a suspected FMD outbreak, thereby offering the possibility of implementing control procedures more rapidly. Such pen-side diagnosis would have particular benefits in FMD emergencies, relevance to FMD control programmes which operate in endemic regions of the world such as South East Asia and for increasing disease awareness in other areas where efforts to control disease may be difficult. In each circumstance the availability of a pen-side device for diagnosis would reduce the necessity for sending routine diagnostic samples to an FMD laboratory and thereby reduce the delay in diagnosis, which can in some areas be considerable.

Animals↗

Failure of vaccination to prevent outbreaks of foot-and-mouth disease.

Outbreaks of foot-and-mouth disease persist in dairy cattle herds in Saudi Arabia despite revaccination at intervals of 4-6 months. Vaccine trials provide data on antibody responses following vaccination. Using this information we developed a mathematical model of the decay of protective antibodies with which we estimated the fraction of susceptible animals at a given time after vaccination. The model describes the data well, suggesting over 95% take with an antibody half-life of 43 days. Farm records provided data on the time course of five outbreaks. We applied a 'SLIR' epidemiological model to these data, fitting a single parameter representing disease transmission rate. The analysis provides estimates of the basic reproduction number R(0), which may exceed 70 in some cases. We conclude that the critical intervaccination interval which would provide herd immunity against FMDV is unrealistically short, especially for heterologous challenge. We suggest that it may not be possible to prevent foot-and-mouth disease outbreaks on these farms using currently available vaccines.

Animals↗

Immediate protection of swine from foot-and-mouth disease: a combination of adenoviruses expressing interferon alpha and a foot-and-mouth disease virus subunit vaccine.

We have previously shown that swine inoculated with recombinant, replication-defective human adenovirus type 5 containing the porcine interferon alpha gene (Ad5-pIFNalpha) are completely protected when challenged 1 day later with virulent foot-and-mouth disease virus (FMDV). In the current study, we examined the duration of protection afforded swine by Ad5-pIFNalpha and the ability of a combination of Ad5-pIFNalpha and a FMDV subunit vaccine delivered by Ad5-A24 (an Ad5 vector containing the capsid coding region of FMDV serotype A24 Cruzeiro and the 3C proteinase coding region of FMDV serotype A12) to induce immediate as well as long-lasting protection against homologous FMDV challenge. Groups of swine were inoculated with Ad5-pIFNalpha and challenged with virulent FMDV A24 1, 3, 5, and 7 days postinoculation (dpi) or 1 day preinoculation. All animals challenged 1 and 3dpi were completely protected from disease. The animals in the remaining groups had either no clinical signs of disease or clinical signs were delayed and less severe compared to the control group. Swine inoculated with a combination of Ad5-pIFNalpha and Ad5-A24 and challenged 5dpi were all completely protected from disease and developed a significant FMDV-specific neutralizing antibody response.

Adenoviridae↗

Comparison of ELISA for the detection of porcine serum antibodies to non-structural proteins of foot-and-mouth disease virus.

Three foot-and-mouth disease virus non-structural protein antibody detection kits, CHEKIT FMD-3ABC, UBI FMD NS EIA and DVIVR NSP ELISA, were compared in the study. The results showed that the specificity of the kits ranged from 96.7 to 100% in nai;ve pigs and from 93.6 to 98.1% in vaccinated pigs, and that the DVIVR kit had the highest analytical sensitivity. The kappa statistics for the detection of 612 sera were 0.582, 0.447 and 0.658 for CHEKIT/UBI, CHEKIT/DVIVR and UBI/DVIVR, respectively. This study also revealed that measurable non-structural protein specific antibodies in some of infected pigs were sustained either for shorter periods or in intermittent patterns, thus aggravating the difficulties associated with the removal of pre-exposed pigs in the field.

Animals↗

Foot-and-mouth disease: susceptibility of domestic poultry and free-living birds to infection and to disease--a review of the historical and current literature concerning the role of birds in spread of foot-and-mouth disease viruses.

Ruminants and pigs are the dominant natural hosts of food-and-mouth disease (FMD) viruses. Approximately 70 additional mammalian species are found to be susceptible under natural or experimental conditions. Reptilia, amphibia, and fish are probably naturally resistant to infection. According to the reviewed literature, domestic birds (chickens, turkeys, guinea fowl, ducks and geese) have been experimentally infected with some strains of FMD viruses and may develop lesions suggestive of FMD such as vesicular lesions on the comb, wattles, eye lids, and feet. Since chickens are to some extent coprophagous, chickens get infected by ingestion of virus under conditions of natural exposure or their plumage gets contaminated in an infectious environment. Thus, domestic birds kept in free-run systems may serve as virus vectors for short distances. Free-living birds, especially starlings (Sturnus vulgaris), sea gulls (Larus canus), house-sparrows (Passer domesticus) have been successfully experimentally infected and developed vesicular lesions on the skin and mucosal membranes of the mouth. During epizootics of FMD the plumage of these free-living birds can be contaminated with FMD viruses and the virus is spread over long distances during migration periods in spring and autumn. Thus migrating birds may assume an active role in long distance dissemination of FMD viruses.

Animals↗