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functional interaction of translation initiation factor eif4g with the foot-and-mouth disease virus internal ribosome entry site.in the life-cycle of picornaviruses, the synthesis of the viral polyprotein is initiated cap-independently at the internal ribosome entry site (ires) far downstream from the 5' end of the viral plus-strand rna. the cis-acting ires rna elements serve as binding sites for translation initiation factors that guide the ribosomes to an internal site of the viral rna. in this study, we show that the eukaryotic translation initiation factor eif4g interacts directly with the ires of foot-and-mouth disea ...200111257179
a single amino acid substitution in nonstructural protein 3a can mediate adaptation of foot-and-mouth disease virus to the guinea pig.the genetic changes selected during the adaptation of a clonal population of foot-and-mouth disease virus (fmdv) to the guinea pig have been analyzed. fmdv clone c-s8c1 was adapted to the guinea pig by serial passage in the animals until secondary lesions were observed. analysis of the virus directly recovered from the lesions developed by the animals revealed the selection of variants with two amino acid substitutions in nonstructural proteins, i(248)-->t in 2c and q(44)-->r in 3a. on further p ...200111264387
nucleotide sequence of genome segment 5 from bombyx mori cypovirus 1.the complete nucleotide sequences of the double-stranded rna genome segments 5 (s5) from bombyx mori cypovirus 1 (bmcpv-1) strains i and h were determined. the segments consisted of 2,852 nucleotides encoding putative proteins of 881 amino acids with molecular masses of approximately 101 kda (p101). a homology search showed that p101 has high similarity (93%) to foot-and-mouth disease virus (fmdv) 2a protease (2apro) at amino acid position 219 to 235. these findings suggest the possibility that ...200111266213
induction of a virus-specific antibody response to foot and mouth disease virus using the structural protein vp1 expressed in transgenic potato plants.we have recently communicated the oral and parental immunogenicity of the structural protein vp1 of foot and mouth disease virus (fmdv) expressed in different transgenic plants. those results clearly indicated the necessity of increasing the expression of the foreign genes in the transgenic plant to avoid additional steps toward the purification and/or concentration of the antigen of interest. here, we report the production of transgenic potatoes plants containing the vp1 gene cloned under the r ...200111270596
role of the cytoplasmic domain of the beta-subunit of integrin alpha(v)beta6 in infection by foot-and-mouth disease virus.field isolates of foot-and-mouth disease virus (fmdv) are believed to use rgd-dependent integrins as cellular receptors in vivo. using sw480 cell transfectants, we have recently established that one such integrin, alpha(v)beta6, functions as a receptor for fmdv. this integrin was shown to function as a receptor for virus attachment. however, it was not known if the alpha(v)beta6 receptor itself participated in the events that follow virus binding to the host cell. in the present study, we invest ...200111287565
outbreak of foot-and-mouth disease virus serotype o in the uk caused by a pandemic strain. 200111292084
analysis of the aphthovirus 2a/2b polyprotein 'cleavage' mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal 'skip'.the 2a region of the aphthovirus foot-and-mouth disease virus (fmdv) polyprotein is only 18 aa long. a 'primary' intramolecular polyprotein processing event mediated by 2a occurs at its own c terminus. fmdv 2a activity was studied in artificial polyproteins in which sequences encoding reporter proteins flanked the 2a sequence such that a single, long, open reading frame was created. the self-processing properties of these artificial polyproteins were investigated and the co-translational 'cleava ...200111297676
the 'cleavage' activities of foot-and-mouth disease virus 2a site-directed mutants and naturally occurring '2a-like' sequences.the 2a/2b cleavage of aphtho- and cardiovirus 2a polyproteins is mediated by their 2a proteins 'cleaving' at their own c termini. we have analysed this activity using artificial reporter polyprotein systems comprising green fluorescent protein (gfp) linked via foot-and-mouth disease virus (fmdv) 2a to beta-glucuronidase (gus) -- forming a single, long, open reading frame. analysis of the distribution of radiolabel showed a high proportion of the in vitro translation products (approximately 90%) ...200111297677
molecular intermediates of fitness gain of an rna virus: characterization of a mutant spectrum by biological and molecular cloning.the mutant spectrum of a virus quasispecies in the process of fitness gain of a debilitated foot-and-mouth disease virus (fmdv) clone has been analysed. the mutant spectrum was characterized by nucleotide sequencing of three virus genomic regions (internal ribosome entry site; region between the two aug initiation codons; vp1-coding region) from 70 biological clones (virus from individual plaques formed on bhk-21 cell monolayers) and 70 molecular clones (rt--pcr products cloned in e. coli). the ...200111297679
[transmission of the foot and mouth disease virus through milk and meat products is not a threat for human health]. 200111338619
antigenicity modulation upon peptide cyclization: application to the gh loop of foot-and-mouth disease virus strain c1-barcelona.foot-and-mouth disease virus (fmdv) isolate c(1)-barcelona (or c-s30) includes four replacements within its immunodominant site (gh loop, residues 136-150 of capsid protein vp1, yttstrgdlahvtat), relative to reference strain c-s8c1 (ytasargdlahlttt). although one of the mutations in c-s30 (147leu-->val) is known to be detrimental for antibody recognition, reactivity of this isolate with the neutralizing monoclonal antibody (mab) 4c4, raised against fmdv c1-brescia (gh loop: ytastrgdlahltat), was ...200111348711
construction of regulatable picornavirus ireses as a test of current models of the mechanism of internal translation initiation.picornavirus internal ribosome entry sites (iress) are approximately 450 nt. rna elements that direct internal initiation of translation, such that when placed between the two cistrons of a dicistronic construct, they drive independent translation of the downstream cistron. consequently they have been widely used for coordinated expression of two or more proteins. all picornavirus iress have an aug triplet at the very 3' end, which is thought to be the actual site of internal ribosome entry. how ...200111350029
the internal ribosome entry site (ires) of hepatitis c virus visualized by electron microscopy.translation of hepatitis c virus (hcv) rna is initiated via the internal ribosome entry site (ires), located within the 5' untranslated region. although the secondary structure of this element has been predicted, little information on the tertiary structure is available. here we report the first structural characterization of the hcv ires using electron microscopy. in vitro transcribed rna appeared as particles with characteristic morphology and gold labeling using a specific oligonucleotide con ...200111350030
inhibition of l-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded rna-dependent protein kinase.we previously demonstrated that the ability of foot-and-mouth disease virus (fmdv) to form plaques in cell culture is associated with the suppression of alpha/beta interferon (ifn-alpha/beta). in the present study, we used escherichia coli-expressed porcine and bovine ifn-alpha or -beta individually to demonstrate that each was equally effective in inhibiting fmdv replication. the block in fmdv replication appeared to be at the level of protein translation, suggesting a role for double-stranded ...200111356957
molecular characterization of foot-and-mouth disease virus isolated from ruminants in taiwan in 1999-2000.in 1999, 10 sporadic outbreaks of cattle foot-and-mouth disease (fmd) occurred in taiwan. by the time, infection was limited to the chinese yellow cattle (a native species of beef cattle in mainland china), which did not develop vesicular lesions under field conditions. five viruses isolates obtained from individual farms were confirmed to be the serotype o fmd virus (o/taiwan/1999). during january-february 2000, however, this virus has spread to dairy cattle and goat herds, causing severe morta ...200111390103
genetic and antigenic analysis of type a foot-and-mouth disease viruses isolated in india during 1987-1996.twenty-three foot-and-mouth disease virus (fmdv) type a field isolates, recovered from different outbreaks during 1987-1996 in india, were subjected to antigenic and genetic analysis. the isolates showed a close antigenic relationship to the current vaccine strain (ind 17/77) in micro-neutralization test conducted using a vaccine strain (ind 17/77) antiserum and a peptide (aa 136-151 of vp1 protein of the a22/azerbaijan/65 strain) antiserum. however, the isolates revealed minor antigenic differe ...200111394573
molecular analysis of peptides from the gh loop of foot-and-mouth disease virus c-s30 using surface plasmon resonance: a role for kinetic rate constants.a foot-and-mouth disease virus (fmdv) field variant, isolate c-s30 (also named c(1)-barcelona), is known to contain four changes within the main antigenic site a (gh loop of capsid protein vp1, residues 136-150), at least one of which (leu147-->val) involves a highly conserved position, critical for antibody recognition in the reference strain c-s8c1. however, immunoenzymatic analysis of fmdv c-s30 showed it was recognised by 4c4, a monoclonal antibody that specifically targets site a. this rema ...200011395136
fmd control strategies. 200111400993
a nonviral peptide can replace the entire n terminus of zucchini yellow mosaic potyvirus coat protein and permits viral systemic infection.systematic deletion and peptide tagging of the amino-terminal domain (nt, ~43 amino acids) of an attenuated zucchini yellow mosaic potyvirus (zymv-agii) coat protein (cp) were used to elucidate its role in viral systemic infection. deletion mutants truncated by 8, 13, and 33 amino acid residues from the cp-nt 5' end were systemically infectious and produced symptoms similar to those of the agii virus. tagging these deletion mutants with either human c-myc (myc) or hexahistidine peptides maintain ...200111413299
foot-and-mouth disease virus can utilize the c-terminal extension of coxsackievirus a9 vp1 for cell infection.foot-and-mouth disease virus (fmdv) is known to employ the conserved arg-gly-asp (rgd) tripeptide located on the variable betag-betah loop of the vp1 capsid protein for binding to cells. coxsackievirus a9 (cav9) also carries an rgd sequence, but on a short c-terminal extension of its vp1 and in a different amino acid context. this apparent relationship raised the question of whether insertion of the heterologous cav9 sequence into fmdv would influence infection by the genetically modified fmdv. ...200111413382
induction of a protective response in swine vaccinated with dna encoding foot-and-mouth disease virus empty capsid proteins and the 3d rna polymerase.this work focuses on the development of a potential recombinant dna vaccine against foot-and-mouth disease virus (fmdv). such a vaccine would have significant advantages over the conventional inactivated virus vaccine, in particular having none of the risks associated with the high security requirements for working with live virus. the principal aim of this strategy was to stimulate an antibody response to native, neutralizing epitopes of empty fmdv capsids generated in vivo. thus, a plasmid (pc ...200111413383
equine rhinitis a virus: structural proteins and immune response.equine rhinitis a virus (erav) is a picornavirus that has been reclassified as a member of the aphthovirus genus because of its resemblance to foot-and-mouth disease virus at the level of nucleotide sequence and overall genomic structure. the n-terminal amino acid sequence of three of the four capsid proteins of erav was determined and showed that the proteolytic cleavage sites within the precursor p1 polypeptide occur exactly as those predicted for an aphthovirus-like 3c protease, which generat ...200111413384
retroviral vector-mediated expression of hoxb4 in hematopoietic cells using a novel coexpression strategy.retroviral vector-mediated expression of the homeoboxgene, hoxb4, in hematopoietic cells has been reported to mediate a benign expansion of gene-modified hematopoietic stem and precursor cells in vivo. in the present study, we used a novel coexpression strategy for coordinated expression of hoxb4 along with a cytoplasmic protein from a retroviral vector. the novel coexpression strategy, based on cotranslational protein separation mediated by the 2a sequence of foot-and-mouth disease virus (fmdv) ...200111420646
recombinant aav vectors containing the foot and mouth disease virus 2a sequence confer efficient bicistronic gene expression in cultured cells and rat substantia nigra neurons.recombinant adeno-associated viruses (raavs) are promising vectors for gene therapy since they efficiently and stably transduce a variety of tissues of immunocompetent animals. the major disadvantage of raavs is their limited capacity to package foreign dna (< or =5 kb). often, co-expression of two or more genes from a single viral vector is desirable to achieve maximal therapeutic efficacy or to track transduced cells in vivo by suitable reporter genes. the internal ribosome entry site (ires) s ...200111423934
gene gun-mediate dna vaccination against foot-and-mouth disease virus.foot-and-mouth disease (fmd) is one of the most dangerous diseases of cloven-hoofed animals and is a constant threat in the middle-east and other regions throughout the world despite intensive vaccination programs. in this work, we describe the ability of fmdv expression constructs to protect pigs from fmdv challenge when used as a vaccine. the construct consists of encephalomyocarditis virus (emcv) internal ribosome entry site (ires), the entire p1 and 2a together with 3cd sequences, all in the ...200111427262
enhancement of the immunity to foot-and-mouth disease virus by dna priming and protein boosting immunization.subunit vaccination is effective in eliciting humoral responses to a variety of viral antigens, however, it has not generated persistent protective immunity to foot-and-mouth disease virus (fmdv). in this study, we observed that priming mice with a dna plasmid encoding vp1 of the fmdv o/taiwan/97 capsid protein followed by boosting with a vp1 peptide conjugate (p29-klh) resulted in production of not only high titers of antibodies but also antibodies with fmdv neutralizing activities. moreover, t ...200111427276
efficient accommodation of recombinant, foot-and-mouth disease virus rgd peptides to cell-surface integrins.the engineering of either complete virus cell-binding proteins or derived ligand peptides generates promising nonviral vectors for cell targeting and gene therapy. in this work, we have explored the molecular interaction between a recombinant, integrin-binding foot-and-mouth disease virus rgd peptide displayed on the surface of a carrier protein and its receptors on the cell surface. by increasing the number of viral segments, cell binding to recombinant proteins was significantly improved. this ...200111444826
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. thes ...200111445149
the non-structural leader protein gene of foot-and-mouth disease virus is highly variable between serotypes.aphthoviruses are unique among picornaviruses in that they alone encode a functional l proteinase as the first component of the viral polyprotein. the l genes of a few indian foot-and-mouth disease viruses were sequenced and compared with those available to study the extent of variation in this gene. besides the two in-frame start codons present in all fmdv l genes, the asia-i vaccine virus had an additional in-frame aug (start) codon, at codon position 3. amino acid sequence comparison revealed ...200111450945
molecular epidemiology of serotype o foot-and-mouth disease virus with emphasis on west and south africa.genetic relationships of serotype o foot-and-mouth disease (fmd) viruses recovered from outbreaks of the disease in the west african countries of niger, burkina faso and, ghana (1988-1993) and those from south africa (2000) were determined by partial vp1 gene characterization. a 581-bp fragment, corresponding to the c-terminus half of the id (vp1 gene) region was amplified and sequenced. an homologous region of 495 nucleotides was ultimately used to determine genetic relationships of serotype o ...200111450953
direct and indirect contact rates among beef, dairy, goat, sheep, and swine herds in three california counties, with reference to control of potential foot-and-mouth disease transmission.to estimate direct and indirect contact rates on livestock facilities and distance traveled between herd contacts.200111453490
evidence of secondary structure by high-resolution magic angle spinning nmr spectroscopy of a bioactive peptide bound to different solid supports.the structure of the 19-amino acid peptide epitope, corresponding to the 141-159 sequence of capsid viral protein vp1 of foot-and-mouth disease virus (fmdv), bound to three different resins, namely, polystyrene-mbha, pega, and poepop, has been determined by high-resolution magic angle spinning (hrmas) nmr spectroscopy. a combination of homonuclear and heteronuclear bidimensional experiments was used for the complete peptide resonance assignment and the qualitative characterization of the peptide ...200111457175
foot-and-mouth disease virus leader proteinase: involvement of c-terminal residues in self-processing and cleavage of eif4gi.the leader proteinase (l(pro)) of foot-and-mouth disease virus frees itself from the nascent polyprotein, cleaving between its own c terminus and the n terminus of vp4 at the sequence lys-leu-lys- downward arrow-gly-ala-gly. subsequently, the l(pro) impairs protein synthesis from capped mrnas in the infected cell by processing a host protein, eukaryotic initiation factor 4gi, at the sequence asn-leu-gly- downward arrow-arg-thr-thr. a rabbit reticulocyte lysate system was used to examine the subs ...200111459842
tricistronic viral vectors co-expressing interleukin-12 (1l-12) and cd80 (b7-1) for the immunotherapy of cancer: preclinical studies in myeloma.synergy between interleukin-12 (il-12) and b7-1 (cd80) for cancer immunotherapy has previously been demonstrated in animal models of breast cancer, lymphoma, and multiple myeloma. with a view to human clinical application, tricistronic retroviral and adenovirus vectors co-expressing il-12 (il-12p40 plus il-12p35) and cd80 were constructed by utilizing two internal ribosome entry site (ires) sequences to link the three cdnas. a murine stem cell virus (mscv)-based retroviral vector (mscv-hil12.b7) ...200111477456
a solid-phase competition elisa for measuring antibody to foot-and-mouth disease virus.a solid-phase competition elisa has been developed to measure antibodies to foot-and-mouth disease (fmd) virus and has been validated using an extensive range of sera from cattle. the assay uses polyclonal antisera and inactivated purified 146s antigens of fmd virus and was compared with the liquid-phase blocking elisa and the virus neutralisation test on a range of serum sets. when examining test sera at a 1:5 dilution with a cut-off point of 30% inhibition of reaction, the solid-phase competit ...200111483215
predicting herd protection against foot-and-mouth disease by testing individual and bulk tank milk samples.four groups of cattle were tested for antibodies against foot-and-mouth disease (fmd) virus type o(1) over three 70 day vaccination cycles using the liquid-phase-blocking-elisa (lpbe). first lactation cows showed the lowest titres and group protection levels (gpls) against fmd virus strains with 'r' values < or =0.5 while second lactation animals gave the highest results. when mean serum titres for each group and sampling date were plotted against gpl a strong correlation was found. revaccinatio ...200111483220
truncated initiation factor eif4g lacking an eif4e binding site can support capped mrna translation.picornavirus proteases cleave translation initiation factor eif4g into a c-terminal two-thirds fragment (hereafter named p100) and an n-terminal one-third fragment, which interacts with the cap-binding factor eif4e. as the timing of this cleavage correlates broadly with the shut-off of host cell protein synthesis in infected cells, a very widespread presumption has been that p100 cannot support capped mrna translation. through the use of an eif4g-depleted reticulocyte lysate system, we show that ...200111483526
activity of the hepatitis a virus ires requires association between the cap-binding translation initiation factor (eif4e) and eif4g.the question of whether translation initiation factor eif4e and the complete eif4g polypeptide are required for initiation dependent on the ires (internal ribosome entry site) of hepatitis a virus (hav) has been examined using in vitro translation in standard and eif4g-depleted rabbit reticulocyte lysates. in agreement with previous publications, the hav ires is unique among all picornavirus iress in that it was inhibited if translation initiation factor eif4g was cleaved by foot-and-mouth disea ...200111483729
detailed analysis of the requirements of hepatitis a virus internal ribosome entry segment for the eukaryotic initiation factor complex eif4f.the hepatitis a virus (hav) internal ribosome entry segment (ires) is unique among the picornavirus iress in that it is inactive in the presence of either the entero- and rhinovirus 2a or aphthovirus lb proteinases. since these proteinases both cleave eukaryotic initiation factor 4g (eif4g) and hav ires activity could be rescued in vitro by addition of eif4f to proteinase-treated extracts, it was concluded that the hav ires requires eif4f containing intact eif4g. here, we show that the inability ...200111483730
foot-and-mouth disease virus: cause of the recent crisis for the uk livestock industry.the recent outbreak of foot-and-mouth disease (fmd) in the united kingdom is a stark reminder of the economic devastation that this disease can wreak. tracing the origin of such an outbreak is an essential part of disease control. modern molecular methods have been in place for a number of years to enable scientists to identify unambiguously the strain of virus responsible. however, tracing the precise origin of such a strain is not so straightforward because the virus can move rapidly around th ...200111485797
[molecular characterization of aphthous fever virus isolated during the years 1993-1994 in argentina].nucleotide sequence and phylogenetic analysis of the vp1 structural protein have been used extensively as diagnostic and epidemiological tools for foot and mouth disease virus (fmdv). in this report we have applied this methodology to the analysis of the vp1 coding sequence from fmdv strains isolated in argentina during 1993-1994. the results demonstrated that the field isolates were related to the vaccine strains used at that time. however the involvement of the vaccine virus appeared to be dif ...200111494760
subcellular distribution of the foot-and-mouth disease virus 3a protein in cells infected with viruses encoding wild-type and bovine-attenuated forms of 3a.picornavirus infection induces the proliferation and rearrangement of intracellular membranes in response to the synthesis of nonstructural proteins, including 3a. we have previously shown that changes in 3a are associated with the inability of a taiwanese strain of foot-and-mouth disease virus (fmdv) (otai) to grow in bovine cells and cause disease in cattle, although the virus grows to high titers in porcine cells and is highly virulent in pigs (c. w. beard and p. w. mason, 2000, j. virol. 74, ...200111504550
hbv core particles as a carrier for b cell/t cell epitopes.in the middle 80s, recombinant hepatitis b virus cores (hbc) gave onset to icosahedral virus-like particles (vlps) as a basic class of non-infectious carriers of foreign immunological epitopes. the recombinant hbc particles were used to display immunodominant epitopes of hepatitis b, c, and e virus, human rhinovirus, papillomavirus, hantavirus, and influenza virus, human and simian immunodeficiency virus, bovine and feline leukemia virus, foot-and-mouth disease virus, murine cytomegalovirus and ...200111509871
[study on the dna vaccine against foot-and-mouth disease virus using the heavy chain constant region of swine igg as the carrier for peptide epitopes].the peptide of amino acids 141-160 of vp1 protein of foot-and-mouth disease virus (fmdv) is a major b cell epitope and the peptide of amino acids 21-40 is an important t cell epitope. in this study, the dna fragments of 141-160 and 21-40 peptide epitopes of a strain of type o fmdv was chemically synthesized and arranged into a tandem repeat 141-160 (20aa)-21-40 (20aa)-141-160 (20aa). this tandem sequence was fused to the 3' end of the heavy chain constant region gene of swine immunoglobulin g an ...200111517610
the generation and persistence of genetic variation in foot-and-mouth disease virus.genetic variation in foot-and-mouth disease virus (fmdv) is of interest for at least two reasons. first, changes to the genes encoding capsid proteins results in antigenic variation, and affects vaccine efficiency and effectiveness of vaccination programs; second, genetic changes can lead to important insights into the transport of virus between countries, regions, herds, and even possibly individuals. current estimates of rna virus mutation rates suggest that an average of about one base mis-in ...200111530198
evidence that equine rhinitis a virus vp1 is a target of neutralizing antibodies and participates directly in receptor binding.equine rhinitis a virus (erav) is a respiratory pathogen of horses and is classified as an aphthovirus, the only non-foot-and-mouth disease virus (fmdv) member of this genus. in fmdv, virion protein 1 (vp1) is a major target of protective antibodies and is responsible for viral attachment to permissive cells via an rgd motif located in a distal surface loop. although both viruses share considerable sequence identity, erav vp1 does not contain an rgd motif. to investigate antibody and receptor-bi ...200111533189
tracing movement of african buffalo in southern africa.genetic characterisation of two pathogens, namely foot and mouth disease (fmd) virus and mycobacterium bovis, isolated from african buffalo (syncerus caffer) in southern africa was used to determine the origin of buffalo in situations where the source of infection was obscure. by determining the phylogenetic relatedness of various fmd virus isolates using partial sequencing of the main antigenic determinant, vp1, the origin of buffalo moved illegally to the non-endemic region of south africa was ...200111548532
efficient virus extinction by combinations of a mutagen and antiviral inhibitors.the effect of combinations of the mutagenic base analog 5-fluorouracil (fu) and the antiviral inhibitors guanidine hydrochloride (g) and heparin (h) on the infectivity of foot-and-mouth disease virus (fmdv) in cell culture has been investigated. related fmdv clones differing up to 10(6)-fold in relative fitness in bhk-21 cells have been compared. systematic extinction of intermediate fitness virus was attained with a combination of fu and g but not with the mutagen or the inhibitor alone. system ...200111559805
ires interaction with translation initiation factors: functional characterization of novel rna contacts with eif3, eif4b, and eif4gii.translation initiation promoted by picornavirus internal ribosome entry site (ires) elements is dependent on the association of specific ires sequences to the initiation factor eif4g. however the rna determinants interacting with other components of the translational machinery are still unknown. in this study, we have identified novel rna-protein interactions between the foot-and-mouth disease virus (fmdv) ires and three translation initiation factors. a doublet of 116/110 kda that crosslinked t ...200111565745
the nature of the bond between peptide and carrier molecule determines the immunogenicity of the construct.the influence of the nature of the bond between a peptide and a (lipidic) carrier molecule on the immunogenicity of that construct was investigated. as types of bonds a thioester-, a disulfide-, an amide- and a thioether bond were investigated. as carrier molecules a peptide, an n-palmitoylated peptide or a c(16)-hydrocarbon chain were used. the biostability of the bond between peptide and carrier molecule is thioether > amide > disulfide >> thioester. however, the immunogenic potency of the con ...200111576330
[point of view of knmvd concerning foot and mouth disease marker vaccine]. 200111596520
[round table discussion about foot and mouth disease prevention and control. the goals and differences of opinion on how to get there]. 200111596536
foot and mouth disease: a revised policy is required. 200111599518
antibody neutralization epitopes and integrin binding sites on nonenveloped viruses. 200111601890
foot-and-mouth disease virus lacking the vp1 g-h loop: the mutant spectrum uncovers interactions among antigenic sites for fitness gain.the arg-gly-asp (rgd) triplet found in the g-h loop of capsid protein vp1 of foot-and-mouth disease virus (fmdv) is critically involved in the interaction of fmdv with integrin receptors and with neutralizing antibodies. multiplication of fmdv c-s8c1 in baby hamster kidney 21 (bhk-21) cells selected variant viruses exploiting alternative mechanisms of cell recognition that rendered the rgd integrin-binding triplet dispensable for infectivity. by constructing chimeric viruses, we show that dispen ...200111601891
inactivation of viruses by aziridines. 200111672893
genetic heterogeneity of sat-1 type foot-and-mouth disease viruses in southern africa.genetic relationships of 50 sat-1 type foot-and-mouth disease viruses were determined by phylogenetic analysis of an homologous 417 nucleotide region encoding the c-terminal half of the vp1 gene and part of the 2a segment. viruses obtained from persistently-infected african buffalo populations were selected in order to assess the regional genetic variation within the host species and compared with ten viruses recovered from recent and historical cases of clinical infection. phylogenetic reconstr ...200111676416
dynamics of the 2001 uk foot and mouth epidemic: stochastic dispersal in a heterogeneous landscape.foot-and-mouth is one of the world's most economically important livestock diseases. we developed an individual farm-based stochastic model of the current uk epidemic. the fine grain of the epidemiological data reveals the infection dynamics at an unusually high spatiotemporal resolution. we show that the spatial distribution, size, and species composition of farms all influence the observed pattern and regional variability of outbreaks. the other key dynamical component is long-tailed stochasti ...200111679661
cleavage of translation initiation factor 4ai (eif4ai) but not eif4aii by foot-and-mouth disease virus 3c protease: identification of the eif4ai cleavage site.the translation initiation factor eif4a is cleaved within mammalian cells infected by foot-and-mouth disease virus (fmdv). the fmdv 3c protease cleaves eif4ai (between residues e143 and v144), but not the closely related eif4aii. modification of eif4ai, to produce a sequence identical to eif4aii around the cleavage site, blocked proteolysis. alignment of mammalian eif4ai onto the three-dimensional structure of yeast eif4a located the scissile bond within an exposed, flexible portion of the molec ...200111682048
foot and mouth disease in human beings. 200111684262
swine vesicular disease virus. pathology of the disease and molecular characteristics of the virion.swine vesicular disease is a highly contagious disease of pigs that is caused by an enterovirus of the family picornaviridae. the virus is a relatively recent derivative of the human coxsackievirus b5, with which it has high molecular and antigenic homology. the disease is not severe, and affected animals usually show moderate general weakening and slight weight loss that is recovered in few days, as well as vesicular lesions in the mucosa of the mouth and nose and in the interdigital spaces of ...200011708597
phylogenetic analysis of foot-and-mouth disease viruses isolated in argentina.we have analysed complete or partial vpi sequences of 31 foot-and-mouth disease (fmd) viruses belonging to serotypes a, o and c to determine the genetic relatedness of field strains of fmd virus (fmdv) that have circulated in argentina between 1961 and 1994. phylogenetic analysis, which also included 15 previously published argentinean sequences and six reference strains, revealed that (i) fmd type a strains showed the highest genetic heterogeneity and could be divided into five lineages with a ...200111724271
epidemiological implications of the molecular characterization of foot-and-mouth disease virus isolated between 1996 and 2000 in bangladesh.foot-and-mouth disease virus was collected during two years throughout bangladesh. viral rna from 40 samples was subjected to reverse transcription-dependent polymerase chain reactions that amplify parts of the capsid protein encoding genome region, and the products obtained were sequenced. this showed that all virus isolates up to january 1999 belonged to a genotype of serotype o, observed here already in 1987, 1996 and 1997, and elsewhere since 1990. in february 2001, this virus variant was in ...200111724275
direct kinetic assay of interactions between small peptides and immobilized antibodies using a surface plasmon resonance biosensor.a surface plasmon resonance (spr) protocol is described for the direct kinetic analysis of small antigenic peptides interacting with immobilized monoclonal antibodies (mab). high peptide concentrations (up to 2.5 microm) and medium mab surface densities (about 1.5 ng/mm(2)) are needed to ensure measurable binding levels, and fast buffer flow rates (60 microl/min) are required to minimize diffusion-controlled kinetics. good reproducibility levels in the kinetic constants are obtained under these ...200211730856
extensive antigenic and genetic variation among foot-and-mouth disease type a viruses isolated from the 1994 and 1995 foci in são paulo, brazil.nine foot-and-mouth disease virus (fmdv) type a isolates recovered from the field fmd foci in são paulo state, brazil, during 1994 and 1995 (a period preceding the last reported focus of fmd in 1996 in this state) were compared among themselves and with the reference vaccine strain a(24)cruzeiro. the techniques used were sandwich elisa, virus neutralization (vn), polyacrylamide gel electrophoresis (page) of the structural polypeptides and direct sequencing of the vp1-coding region (1d gene). res ...200211731156
how rna viruses exchange their genetic material.one of the most unusual features of rna viruses is their enormous genetic variability. among the different processes contributing to the continuous generation of new viral variants rna recombination is of special importance. this process has been observed for human, animal, plant and bacterial viruses. the collected data reveal a great susceptibility of rna viruses to recombination. they also indicate that genetic rna recombination (especially the nonhomologous one) is a major factor responsible ...200111732610
sensitivity of primary cells immortalised by oncogene transfection for the detection and isolation of foot-and-mouth disease and swine vesicular disease viruses.primary cells derived from calf thyroid (cty), calf kidney (ck) and piglet kidney (pk) were immortalised by oncogene transfection and their susceptibility to infection by foot-and-mouth disease (fmd) virus and swine vesicular disease (svd) virus examined. eighty-five immortalised cell lines (47 cty, 20 ck and 18 pk) proved stable upon repeated cell culture passage and many supported the growth of fmd virus and several of the pk cell lines supported svd virus. however, none of the immortalised li ...200211750139
anti-3ab antibodies in the chinese yellow cattle infected by the o/taiwan/99 foot-and-mouth disease virus.the o/taiwan/99 foot-and-mouth disease virus (fmdv), a south asian topotype of serotype o, was introduced into taiwan in 1999. the chinese yellow cattle infected by the virus did not develop clinical lesions under experimental and field conditions. a blocking enzyme-linked immunosorbent assay (elisa) kit with the 3ab antigen, a polypeptide of fmdv non-structural (ns) proteins, was used to evaluate the development and duration of anti-3ab antibodies, proving active viral replication, in the chine ...200211750140
diagnosis of foot-and-mouth disease by real-time fluorogenic pcr assay. 200111761294
the eradication of foot-and-mouth disease: a parallel problem.poliomyelitis and foot-and-mouth disease (fmd) can both be prevented by vaccination. the vaccines are highly effective but they differ in that, whereas in most countries attenuated viruses have been used to control poliomyelitis, fmd vaccines are prepared from the virulent viruses. the reasons for choosing inactivated vaccines for fmd are (i) the demonstration several decades ago that a virus which was attenuated for one species could be virulent for another and (ii) the great antigenic variabil ...200111763321
[preventive vaccination against foot and mouth disease not a realistic scenario?]. 200111766538
integrin alphavbeta1 is a receptor for foot-and-mouth disease virus.infection by field strains of foot-and-mouth disease virus (fmdv) is initiated by binding to certain species of arginine-glycine-aspartic acid (rgd)-dependent integrin including alphavbeta3 and the epithelial integrin alphavbeta6. in this report we show that the integrin alphavbeta1, when expressed as a human/hamster heterodimer on transfected chob2 cells, is a receptor for fmdv. virus binding and infection mediated by alphavbeta1 was inefficient in the presence of physiological concentrations o ...200211773368
sequence analysis of recent indian isolates of foot-and-mouth disease virus serotypes o, a and asia 1 from clinical materials.partial nucleotide sequences of 1d gene of 38 isolates of foot-and-mouth disease virus (fmdv) of serotypes o, a and asia 1 originating from various parts of india were determined. field materials were subjected straight to rna extraction, reverse transcription - pcr (rt-pcr) and sequencing. also 3 fmdv vaccine strains, ind r2/75 (serotype o), ind 63/72 (serotype asia 1) and ind 17/77 (serotype a) were included in the analysis. the seqences were compared mutually as well as with available corresp ...200111774894
[vaccination against foot and mouth disease: a biotechnical approach?].described is how through a biotechnical approach a fmd 'marker' vaccine and matching diagnostic test could be developed which makes it possible to control fmd safety and effectively. much research is still necessary but important in this is that the european union supports these developments.200111780258
duration and fitness dependence of quasispecies memory.the duration and fitness dependence of memory in viral quasispecies evolving in cell culture have been investigated using two genetic markers of foot-and-mouth disease virus (fmdv). in lineages of antigenic variant fmdv red, which reverted to fmdv rgd, memory fmdv red genomes were detected after 50 infectious cycles, and memory level was fitness dependent. in growth-competition experiments between a reference fmdv rgd and two different fmdv red populations, a 7.6-fold higher fitness of the initi ...200211786012
serological evidence of fmd subclinical infection in sheep population during the 1999 epidemic in morocco.during 1999, 11 outbreaks of foot and mouth disease (fmd) were declared in the east and central part of morocco. all the fmd clinical cases reported were cattle. in order to analyse the serological status of sheep from the fmd outbreak areas, 598 sheep sera were tested using a liquid-phase blocking elisa (lpbe) to detect antibodies against fmdv structural proteins. the study confirmed the presence of fmdv specific antibodies in 77 clinically normal sheep, indicating that unrecognised fmdv-infect ...200211792487
a novel methodology to develop a foot and mouth disease virus (fmdv) peptide-based vaccine in transgenic plants.the expression of antigens in transgenic plants has been increasingly used as an alternative to the classical methodologies for antigen expression in the development of experimental vaccines. however, an important limitation in most cases is the low concentration of the recombinant antigens in the plant tissues, which reduces the possibilities of practical applications. because the site of insertion of the transferred dna into the cellular chromosomal dna is at random, different levels of foreig ...200211803075
integrity of gh-loop of foot-and-mouth disease virus during virus inactivation: detection by epitope specific antibodies.vaccine against foot-and-mouth disease (fmd) is prepared after inactivating the virus produced in cell culture. inactivation of the fmd virus (fmdv) was earlier done by formaline. however, several vaccine outbreaks, which occurred in europe revealed that the formaline treatment is not highly effective for virus inactivation. subsequently, binary ethyleneimine (bei) was identified as an effective inactivation reagent for fmdv. however, these chemical reagents are likely to have effect on whole vi ...200211803078
diagnosis of foot-and-mouth disease by rt-pcr: use of phylogenetic data to evaluate primers for the typing of viral rna in clinical samples.the results of type-specific rt-pcr diagnostic assays on foot-and-mouth disease (fmd) viruses in clinical samples were mapped onto serotype-specific dendrograms representing the degree of nucleotide sequence variation between the fmd virus isolates. this novel approach assisted the selection of suitable pcr primer sets for the diagnosis of fmd virus isolates belonging to different topotypes within each serotype. these interpretations were qualified by using a universal (fmd virus group) specific ...200111811689
resistance to extinction of low fitness virus subjected to plaque-to-plaque transfers: diversification by mutation clustering.plaque-to-plaque transfers of rna viruses lead to accumulation of mutations and fitness decrease. to test whether continuing plaque-to-plaque transfers would lead to viral extinction, we have subjected several low fitness foot-and-mouth disease virus (fmdv) clones to up to 130 successive plaque transfers, and have analyzed the evolution of plaque titers and genomic nucleotide sequences. no case of viral extinction could be documented. some low fitness clones that posses an internal poly(a) tract ...200211812137
conserved rna secondary structures in picornaviridae genomes.the family picornaviridae contains important pathogens including, for example, hepatitis a virus and foot-and-mouth disease virus. the genome of these viruses is a single messenger-active (+)-rna of 7200-8500 nt. besides coding for the viral proteins, it also contains functionally important rna secondary structures, among them an internal ribosomal entry site (ires) region towards the 5'-end. this contribution provides a comprehensive computational survey of the complete genomic rnas and a detai ...200111812840
[diagnosis of foot and mouth disease].because foot-and-mouth disease has the potential for an explosive spread, instant and reliable diagnosis is of special importance. in this article the clinical examination, types and shipment of samples as well as the current methods of laboratory diagnosis by detection of fmd-virus, antigen, nucleic acid and antibodies are reviewed. special emphasis is laid on the differentiation between vaccinated and infected animals, in respect to conventional as well as novel vaccines.200111822165
[persistence of fdmv and its effects on disease control strategies].it is well-known that foot-and-mouth disease virus (fmdv) causes a persistent infection, lasting for more than 28 days, in cattle, sheep, goat as well as some other ruminant species, but not in pigs. although convincing evidence for virus transmission is missing, these carrier animals have to be considered as a potential risk of infection. some aspects of fmdv persistence are presented and discussed with regard to disease control strategies.200111822166
[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 an ...200111822168
synthetic peptide-based vaccine and diagnostic system for effective control of fmd.we have designed synthetic peptides corresponding to two different regions of the genome of foot-and-mouth disease virus (fmdv) that are effective as (a) a vaccine or (b) a diagnostic reagent which differentiates convalescent from vaccinated animals, respectively. the peptide vaccine is based on a sequence from the prominent g-h loop of vp1, one of the four capsid proteins. the sequence was optimized by the inclusion of a cyclic constraint and adjoining sequences, and broader immunogenicity was ...200111851319
synthetic peptide vaccines: unexpected fulfillment of discarded hope?in the early eighties it was realized that the ultimate vaccine would be a synthetic peptide. major efforts were put into the development of a synthetic vaccine for foot-and-mouth disease virus (fmdv) for which even today no alternative exists besides the classical vaccine based on inactivated virus. despite impressive progress, a peptide vaccine that could match the classical vaccine with respect to efficacy (i.e. full protection of all animals after a single vaccination) has not materialized. ...200111851321
synthetic peptides as functional mimics of a viral discontinuous antigenic site.functional reproduction of discontinuous antigenic site d of foot-and-mouth disease virus (fmdv) has been achieved by means of synthetic peptide constructions that integrate into a single molecule each of the three protein loops that define the antigenic site. the site d mimics are designed on the basis of the x-ray structure of fmdv type c-s8c1 with the aid of molecular dynamics, so that the five residues assumed to be involved in antigenic recognition are located on the same face of the molecu ...200111851326
isolation of foot-and-mouth disease virus from japanese black cattle in miyazaki prefecture, japan, 2000.four outbreaks of foot-and-mouth disease (fmd) occurred from march to may 2000 in miyazaki and hokkaido prefectures, japan. fmd virus isolation was achieved by sampling probang materials from japanese black cattle in the third case found in miyazaki prefecture. the probang materials were inoculated to bovine kidney (bk) and bovine thyroid cell cultures. cpe was observed in the bk at two days post-inoculation. specific amplified dna segments for fmd virus (fmdv) were detected by reverse transcrip ...200211853156
genetic diversity in the vp1 gene of foot-and-mouth disease virus serotype asia 1.complete nucleotide sequence of the 1d (vp1-encoding) gene of 61 foot-and-mouth disease (fmd) serotype asia i virus isolates recovered from different outbreaks in india between 1985 and 1999 including two vaccine strains currently used were determined. the sequences were compared with each other and those from other asian countries. on the basis of phylogenetic analysis the viruses could be grouped into four genotypes (genotypes i-iv). all the 61 isolates from india belong to a single genotype ( ...200211855637
[foot and mouth disease in (meat)calves: clinical signs and viral shedding]. 200211858041
a review of emergency foot-and-mouth disease (fmd) vaccines.the primary objectives of this paper are to describe emergency foot-and-mouth disease (fmd) vaccines and review literature on emergency vaccine efficacy to protect animals against (1) clinical signs and (2) infection (local virus replication). the reviewed experiments suggest that in cattle, sheep and pigs, the vaccine could be effective in preventing disease within 4-5 days post-vaccination. these studies also suggest that the risk of spreading infection decreases as the interval between vaccin ...200211858856
early protection against homologous challenge after a single dose of replication-defective human adenovirus type 5 expressing capsid proteins of foot-and-mouth disease virus (fmdv) strain a24.previously we demonstrated that two doses of a replication-defective human adenovirus serotype 5 (ad5) carrying the capsid (p1) and 3c protease coding regions of a laboratory strain of fmdv (a12) completely protected five of six swine challenged with homologous virus. the objective of the current study was to evaluate the efficacy of one dose of an ad5-vectored vaccine expressing the p1 coding region of an fmdv field strain. a replication-defective ad5 containing the p1 coding region of fmdv a24 ...200211858872
could foot and mouth disease be a biological warfare incident? 200211873548
emergence and selection of rna virus variants: memory and extinction.two features of viral quasispecies are reviewed: the presence of memory genomes as minority components of their mutant spectra, and viral extinction due to enhanced mutagenesis. memory has been documented with several genetic markers of the important animal picornavirus foot-and-mouth disease virus (fmdv). the presence of memory genomes in viral quasispecies may accelerate their adaptive response whenever a selective constraint has already been experienced by a viral population during previous s ...200211885948
a replication-competent chimera of plant and animal viruses.human, animal, fungal, and plant viruses encode papain-like proteinases that function in polyprotein processing, rna synthesis, and virus-host interactions. to compare the functional profiles of diverse papain-like proteinases, we replaced a proteinase gene of the beet yellows virus (byv) with those derived from equine arteritis virus (eav), foot-and-mouth disease virus (fmdv), and the fungal virus chv1. we found that, although each of the foreign proteinases efficiently processed the viral poly ...200211886267
coexpression of interleukin-12 chains by a self-splicing vector increases the protective cellular immune response of dna and mycobacterium bovis bcg vaccines against mycobacterium tuberculosis.more effective vaccines against mycobacterium tuberculosis may contribute to the control of this major human pathogen. dna vaccines encoding single mycobacterial proteins stimulate antimycobacterial t-cell responses and induce partial protection against m. tuberculosis in animal models. the protective efficacy of these vaccines encoding a single antigen, however, has been less than that afforded by the current vaccine, mycobacterium bovis bacillus calmette-guérin (bcg). the heterodimeric cytokin ...200211895958
[the contagiousness of the pestivirus and foot and mouth disease virus]. 200211905240
antigenic sites of foot-and-mouth disease virus (fmdv): an analysis of the specificities of anti-fmdv antibodies after vaccination of naturally susceptible host species.of the known neutralizing antigenic sites of foot-and-mouth disease virus (fmdv), site 1 or a, formed in part by the g-h loop of vp1, has historically been considered immunodominant because of evidence implicating its importance in the induction of a protective immune response. however, no systematic study has been done to determine the relative importance of the various specificities of antibodies against the known neutralizing antigenic sites of fmdv in the polyclonal immune response of a natu ...200211907326
functional mimicry of a discontinuous antigenic site by a designed synthetic peptide.functional reproduction of the discontinuous antigenic site d of foot-and-mouth disease virus (fmdv) has been achieved by means of synthetic peptide constructions that integrate each of the three protein loops that define the antigenic site into a single molecule. the site d mimics were designed on the basis of the x-ray structure of fmdv type c-s8c1 with the aid of molecular dynamics, so that the five residues assumed to be involved in antigenic recognition are located on the same face of the m ...200211921395
mechanisms of integrin-mediated virus attachment and internalization process.viruses that propagate within vertebrate hosts have adapted many strategies to infect host cells. one of the first steps in a viral infection is the binding of the virus to cell surface molecules. this interaction between a virus and its receptors plays a key role in the multiplication cycle. entry of viruses into cells is a complex, multistep process, and for several viruses, cell attachment and internalization are distinct steps. a number of virus receptors have been identified; a common famil ...200111922076
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