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At least 919 records · Page 51Linked to original sources
PubMed2005

The alpha(v)beta6 integrin receptor for Foot-and-mouth disease virus is expressed constitutively on the epithelial cells targeted in cattle.

Field strains of Foot-and-mouth disease virus (FMDV) use a number of alpha(v)-integrins as receptors to initiate infection on cultured cells, and integrins are believed to be the receptors used to target epithelial cells in animals. In this study, immunofluorescence confocal microscopy and real-time RT-PCR were used to investigate expression of two of the integrin receptors of FMDV, alpha(v)beta6 and alpha(v)beta3, within various epithelia targeted by this virus in cattle. These studies show that alpha(v)beta6 is expressed constitutively on the surfaces of epithelial cells at sites where infectious lesions occur during a natural infection, but not at sites where lesions are not normally formed. Expression of alpha(v)beta6 protein at these sites showed a good correlation with the relative abundance of beta6 mRNA. In contrast, alpha(v)beta3 protein was only detected at low levels on the vasculature and not on the epithelial cells of any of the tissues investigated. Together, these data suggest that in cattle, alpha(v)beta6, rather than alpha(v)beta3, serves as the major receptor that determines the tropism of FMDV for the epithelia normally targeted by this virus.

Animals↗
PubMed2004

Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro.

Foot-and-mouth disease virus (FMDV) induces a very rapid inhibition of host cell protein synthesis within infected cells. This is accompanied by the cleavage of the eukaryotic translation initiation factor 4GI (eIF4GI). The cleavage of the related protein eIF4GII has now been analyzed. Within FMDV-infected cells, cleavage of eIF4GI and eIF4GII occurs with similar kinetics. Cleavage of eIF4GII is induced in cells and in cell extracts by the FMDV leader protease (L(pro)) alone, generating cleavage products similar to those induced by enterovirus and rhinovirus 2A protease (2A(pro)). By the use of a fusion protein containing residues 445 to 744 of human eIF4GII, it was demonstrated that the FMDV L(pro) specifically cleaves this protein between residues G700 and S701, immediately adjacent to the site (V699/G700) cleaved by rhinovirus 2A(pro) in vitro. The G700/S701 cleavage site does not correspond, by amino acid sequence alignment, to that cleaved in eIF4GI by the FMDV L(pro) in vitro. Knowledge of the cleavage sites and the three-dimensional structures of the FMDV L(pro) and rhinovirus 2A(pro) enabled mutant forms of the eIF4GII sequence to be generated that are differentially resistant to either one of these proteases. These results confirmed the specificity of each protease and showed that the mutant forms of the fusion protein substrate retained their correct sensitivity to other proteases.

Amino Acid Sequence↗
PubMed1992

Modulation of T-cell reactivity to synthetic peptide analogues of foot-and-mouth disease virus in sheep by amino acid substitutions.

The ability of synthetic peptide analogues of foot-and-mouth disease virus VP1 capsid protein to induce T-cell proliferation in vitro following immunization of sheep with the uncoupled peptides was assessed. Elevated T-cell responses were obtained to a 21-residue peptide containing VP1 residues 141-158, and a 40-residue peptide containing residues 200-213 and 141-158 linked via a diproline-serine spacer. In contrast, no significant T-cell response was obtained with a 19-residue peptide containing residues 200-213 alone. In an attempt to engineer T-cell reactivity to this peptide, a sequence motif found in many peptides recognized by human or mouse T-cells was introduced by amino acid substitution. Substitution of a glycine or an aspartic acid for an alanine at position 207 in the 19-residue peptide resulted in the introduction of two such motifs running consecutively. Immunization of sheep with these peptides resulted in significant T-cell proliferative responses and elevated antibody responses. Analysis of further sequence variants showed that T-cell responsiveness was maintained with peptides containing single amino acid changes within these motifs, provided position 207 was glycine. The results thus suggest that increased T-cell reactivity, might be engineered via sequence manipulation of the 200-213 component of the 40-residue synthetic peptide. Such an additional T-cell epitope in the 40-residue peptide could potentially result in superior neutralizing antibody responses directed against the major epitope in residues 141-160 of VP1.

Amino Acid Sequence↗
PubMed1999

Enterovirus 71 from fatal and nonfatal cases of hand, foot and mouth disease epidemics in Malaysia, Japan and Taiwan in 1997-1998.

Enterovirus 71 (EV71), one of the major causative agents for hand, foot and mouth disease (HFMD), is sometimes associated with severe central nervous system diseases. In 1997, in Malaysia and Japan, and in 1998 in Taiwan, there were HFMD epidemics involving sudden deaths among young children, and EV71 was isolated from the HFMD patients, including the fatal cases. The nucleotide sequences of each EV71 isolate were determined and compared by phylogenetical analysis. EV71 strains from previously reported epidemics belonged to genotype A-1, while those from recent epidemics could be divided into two genotypes, A-2 and B. In Malaysia, genotype A-2 was more prevalent, while in Japan and Taiwan, B genotype was more prevalent. Two isolates from fatal cases in Malaysia and one isolate from a fatal case in Japan were genotype A-2. However, all isolates from three fatal cases in Taiwan belonged to genotype B. The severity of the HFMD did not link directly to certain genotypes of EV71.

DNA Primers↗
PubMed1999

Genetic analysis of type O viruses responsible for epidemics of foot-and-mouth disease in North Africa.

The nucleotide sequences of the 3' end of the capsid-coding region were determined for 30 serotype O foot-and-mouth disease (FMD) viruses isolated between 1987 and 1994 from outbreaks in North Africa and the Middle East. These sequences were compared with the previously published sequences of 9 field virus isolates from the Middle East and 5 vaccine virus strains, 3 of which originated from the Middle East (O1/Turkey/Manisa/69, O1/Sharquia/Egypt/72 and O1/Israel/2/85) and 2 from Europe (O1/Lausanne/Switzerland/65 and O2/Brescia/Italy/47). Cluster analysis of these sequences using the unweighted pair group mean average (UPGMA) method showed: (i) that the FMD viruses isolated from North Africa and the Middle East were very different from the classical European vaccine strains; (ii) that all the viruses isolated during the 1989-92 North African epidemic formed a cluster differing by no more than 6% from each other; (iii) a virus isolated in Libya in 1988 was unrelated to the aforementioned epidemic; and (iv) viruses from a second, less extensive epidemic, occurring in 1994, fell into yet another cluster.

Africa, Northern↗
PubMed2003

A synthetic peptide containing the consensus sequence of the G-H loop region of foot-and-mouth disease virus type-O VP1 and a promiscuous T-helper epitope induces peptide-specific antibodies but fails to protect cattle against viral challenge.

A pilot study was carried out in cattle to determine the immunogenicity of a synthetic consensus peptide comprising the G-H loop region of foot-and-mouth disease virus (FMDV) type-O VP1 and a non-VP1 T-helper (Th) epitope. Cattle vaccinated intramuscularly either once (n = 5) or twice (n = 4) with 50 microg of the peptide preparation at a 21-day interval developed antibodies to the peptide as determined by ELISA with the exception of one steer that received a single dose. However, neutralizing antibody titers against FMDV type-O were modest and all animals presented with clinical FMD signs upon challenge 21 days after the last vaccination. In contrast, four of the five animals inoculated with an inactivated FMD type-O commercially prepared vaccine developed neutralizing antibodies and were fully protected against clinical disease following virus challenge 21 days post-vaccination (dpv). Nucleotide sequence comparison of the VP1 region between the challenge virus and RT-PCR products recovered from a lesion of the peptide-vaccinated animal with the highest neutralizing antibody titer 5 days post-challenge (dpc) showed no evidence for selection of a neutralization-resistant mutant. We conclude that although the synthetic peptide induced an antibody response in cattle, it failed to confer protection against FMDV challenge.

Amino Acid Sequence↗
PubMed1995

A 10-amino-acid linear sequence of VP1 of foot and mouth disease virus containing B- and T-cell epitopes induces protection in mice.

The area of foot and mouth disease virus (FMDV) comprising residues 140 and 160 of capsid protein VP1 has been used extensively as an immunogen in natural and experimental hosts. A detailed epitope mapping of this region, however, has not been reported. For this purpose a synthetic peptide containing the residues 135 to 160 (p135-160) of VP1 of FMDV O1 Campos was analyzed for its T- and B-cell epitopes. The p135-160 is highly immunogenic, either by itself or coupled to a carrier protein (BSA), elicits a long-lasting neutralizing antibody response in mice, and provides solid protection against virulent challenge. By using a set of synthetic 10mer overlapping peptides, which cover the entire sequence 135-160 of VP1, we have shown that at least four discrete B epitopes are regularly distributed along the peptide. Although immunization with each of the 10mers coupled with BSA as a carrier protein induced peptide-specific antibody responses, individually none of the 10mers was able to induce neutralizing antibodies. However, anti-135-160 antibodies sorted by immunoaffinity chromatography using each of the 10mers revealed the existence of at least four discrete neutralizing sites: one spanning residues 135-144, at least two more between residues 140 and 154, and another in the region 150-160. Moreover, T-cell epitopes were identified, both by antigen-dependent proliferation assays and by adoptive cell transfer. By both methods, a T-cell epitope was located in the area comprising residues 135-144; the cell transfer experiment, which seems to be more sensitive, also identified a second T-cell epitope between residues 150 and 160. Interestingly, when the region 135-144, which contains both B- and T-cell epitopes, was in a tandem repeat configuration it induced a strong neutralizing antibody response in mice and solid protection against the challenge.

Amino Acid Sequence↗
PubMed2006

High throughput sequencing and comparative genomics of foot-and-mouth disease virus.

Despite a basic understanding of many aspects of FMD biology, much information regarding FMDV virulence, host range, and virus transmission remains poorly understood. Here we present how the use of high throughput sequencing for complete genome sequences of foot-and mouth disease virus (FMDV) led to a series of new insights into viral genome sequence conservation and variability, genetic diversity in nature and phylogenetic classification of isolates, including the first complete sequences of the South African Territories type 1 and 3 (SAT1 and SAT3) genomes. Comparative genomic analysis of full-length sequences of FMDV isolates did allow: (i) the identification of highly conserved regulatory or coding regions which are critical for aspects of virus biology as well as novel viral genomic motifs with likely biological relevance; (ii) characterization of the first complete sequences of the SAT1 and SAT3 genomes; (iii) identification of a novel SAT virus lineage genetically distinct from other SAT and Euro-Asiatic lineages; (iv) precise identification of strains circulating around the world for epidemiological and forensic attribution; (v) assessment of mutation and recombination processes as mechanisms equally involved in evolution; (vi) mutation rates, tolerance and constraints of genes and proteins during evolution of FMD viruses during in vivo replication and (vi) support for the hypothesis of a new evolutionary model.

Animals↗
PubMed1994

Analysis of sites of foot and mouth disease virus persistence in carrier cattle via the polymerase chain reaction.

This study was undertaken in order to explore possible sites of foot-and-mouth disease virus (FMDV) persistence during the carrier state. Tissue samples taken from experimentally infected animals at different times post-infection (p.i.) were examined by conventional viral isolation and the polymerase chain reaction (PCR) technique. The analysis of samples from several organs taken from 17 bovines between 3 and 270 days p.i. allowed the following conclusions: 1) Virus present in oesophageal-pharyngeal fluids (OPF) during the carrier state originates in the pharynx as shown by the detection of antisense FMDV RNA by PCR, 2) PCR is more sensitive than standard virus isolation techniques and may be used for the rapid detection of FMDV in specimens obtained during the acute stage of FMD and for identification of persistently infected cattle.

Animals↗
PubMed2003

A recombinant fusion protein and DNA vaccines against foot-and-mouth disease virus type Asia 1 infection in guinea pigs.

On the basis of amino acid (aa) sequence of the tandem repeat 133-158-20-34-133-158 which consisted of aa 133-158 of VP1 and aa 20-34 of VP4 of Foot-and-mouth disease virus (FMDV) type Asia 1 a recombinant prokaryotic expression vector pAS1-P encoding a fusion protein and eukaryotic expression vectors pAS1-E and pAS1-EdeltaCpG-ODN representing DNA vaccines were constructed. Guinea pigs immunized with these vaccines showed both neutralizing antibody and T cell proliferation responses. FMDV challenge tests for the first time showed that the recombinant fusion protein and pAS1-E and pAS1-EdeltaCpG-ODN vaccines protected 86%, 60% and 43% of guinea pigs from FMDV type Asia1 challenge, respectively. The results also indicated that the immune response of animals treated with the vector pAS1-E containing an oligodeoxynucleotide (ODN), which consisted of immunostimulatory cytosine-phosphate-guanosine (CpG) motifs, was augmented by CpG ODN.

Animals↗
PubMedDate not supplied

The application of biotechnology to the control of foot-and-mouth disease virus.

Biotechnology, which less than 10 years ago was heralded as an alternative to epidemiology in providing the answers to the control of foot-and-mouth disease (FMD), has not fulfilled its initial promise. Instead it is now complementing epidemiology by providing extremely sensitive and specific tools for identifying and characterizing strains of FMD virus in diagnostic material. Considerable advances in our understanding of the evolution of the virus in different field situations has been made possible by the development and application of polymerase chain reaction and nucleotide sequencing techniques. The individual genes of FMD virus can now be cloned into a number of vectors and separately expressed and studied in isolation from the other viral proteins. Biotechnology has not provided a safe and effective vaccine to replace the conventional tissue culture derived vaccine that would have made FMD a disease of the past. FMD remains the most economically significant animal disease having a major influence on the international trade of animals and their products. The world distribution of FMD has remained almost unchanged over the last 20 years and a balance has been maintained between improved surveillance and diagnostic technology and the ever increasing legal and illegal international movement of animals and reduction in veterinary resources. Research continues on peptide, recombinant and vector expressed virus protein vaccines which could at any time yield a breakthrough, not only for FMD control but, using similar technology, for control of other viral diseases, human and animal. Until this occurs, control and eradication of FMD still relies on classical epidemiological techniques, making use of new biotechnological methods.

Animals↗
PubMed2005

Predictions for the timing and use of culling or vaccination during a foot-and-mouth disease epidemic.

First-fortnight incidence (FFI) is a modelling parameter that can be used to predict both the prevalence and duration of a foot-and-mouth disease (FMD) epidemic at regional and national levels. With an indication of how long an epidemic may last by the end of week two, it becomes possible to estimate whether vaccination would be economically viable from the start of an epidemic. Where FFI indicates that an epidemic is unlikely to last for as long as an export ban on agricultural produce, it may be inappropriate to implement a policy of 'vaccination to live'. Alternatively where FFI indicates that an epidemic will equal or exceed the ban length, then the benefits of vaccination should be considered at an early stage, during or after the first fortnight. Since blanket vaccination of the national or regional herds and flocks would be both costly and heighten the risk of producing carrier animals, targetting vaccination through risk assessment becomes useful.

Animal Husbandry↗
PubMed1988

Failure of Haematobia thirouxi potans (Bezzi) to transmit foot-and-mouth disease virus mechanically between viraemic and susceptible cattle.

In 2 separate experiments the blood-feeding fly Haematobia thirouxi potans (Bezzi) failed to transmit foot-and-mouth disease virus when transferred from viraemic (log 2,6-log 4,3 MLD50 or TCID50/ml) to susceptible cattle. Each experiment involved 2 susceptible and 2 viraemic animals housed in separate stables and 2,000-4,000 flies of which most had fed on viraemic hosts 120 min prior to transfer. Furthermore, only minimal quantities of virus were isolated from free-living flies captured on experimentally infected buffalo (Syncerus caffer) in the acute stages of infection.

Animals↗
PubMed2005

Enhanced immunogenicity of microencapsulated multiepitope DNA vaccine encoding T and B cell epitopes of foot-and-mouth disease virus in mice.

The role of poly(D,L-lactic-co-glycolic acid, PLGA) microparticles on enhancing immune responses of multiepitope DNA vaccines was investigated in vitro and in vivo. pcDNA-SG encoding T and B cell epitopes of foot-and-mouth disease virus (FMDV) was encapsulated into PLGA microparticles. PLGA microparticles could protect themselves from nuclease degradation in vitro. PLGA-pcDNA-SG microparticles could be uptaken by cells and expressed His-tagged SG immunogen in vitro and in vivo. A prolonged expression and presentation of SG immunogen were observed by confocal laser scanning microscopy in the lymphocytes from the mice incubated with PLGA-pcDNA-SG microparticles, compared with the mice immunized with naked pcDNA-SG. PLGA-pcDNA-SG microparticles displayed a significant stronger immunogenicity than naked DNA vaccines with a higher titer of virus-specific antibody, elevated IFN-gamma production and enhanced lymphocyte proliferation. PLGA-DNA microparticle could elicit augmented humoral and cellular responses with reduced amounts and times of immunization.

Animals↗
PubMed1994

Rapid coagglutination test for the detection and typing of foot and mouth disease virus.

Protein A containing Staphylococcus aureus was used to develop a coagglutination (COA) test for the detection and typing of foot and mouth disease virus (FMDV) O, A and C serotypes in infected cells and tissues. Different batches and amounts of guinea pig anti-FMDV sera were assessed to optimize the preparation of COA conjugates. The sensitivity and specificity of the COA Test for the detection of FMDV O, A and C serotypes and heterologous viruses was also characterized. Comparison between the COA Test and complement fixation test for the detection and typing of FMDV obtained from extracts of tongue epithelial tissues from infected cattle revealed high agreement in the results and indicated a potential application of the COA Test for the direct diagnosis of viruses.

Agglutination Tests↗
PubMed2006

Simulation analyses to evaluate alternative control strategies for the 2002 foot-and-mouth disease outbreak in the Republic of Korea.

Using the stochastic and spatial simulation model of between-farm spread of disease, InterSpread Plus, we evaluated the effect of alternative strategies for controlling the 2002 epidemic of foot-and-mouth disease (FMD) in the Republic of Korea. InterSpread Plus was parameterised to simulate epidemics of FMD in the population of farms containing susceptible animal species in the Korean counties of Yongin, Icheon, Pyongtaek, Anseong, Eumseong, Asan, Cheonan, and Jincheon. The starting point of our analyses was the simulation of a reference strategy, which approximated the real epidemic. The results of simulations of alternative epidemic-control strategies were compared with this reference strategy. Ring vaccination (when used with either limited or extended pre-emptive depopulation) reduced both the size and variability of the predicted number of infected farms. Reducing the time between disease incursion and commencement of controls had the greatest effect on reducing the predicted number of infected farms.

Animals↗
PubMed1990

Detection of T1-oligonucleotides of the foot-and-mouth disease virus RNA [correction of DNA] by silver staining.

Viral (v) RNA was isolated from purified foot-and-mouth disease virus (FMDV) by phenol-chloroform-isoamylalcohol treatment, digested by RNase T1 and separated by one-dimensional polyacrylamide gel electrophoresis (PAGE). The oligonucleotides were detected by silver staining. About 45 micrograms of vRNA corresponding to about 100 ml of infectious BHK-21 cell culture fluid yielded a pattern of nearly 20 bands sufficient to differentiate between the FMD viruses.

Animals↗