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differential effects of viral vectors on migratory afferent lymph dendritic cells in vitro predicts enhanced immunogenicity in vivo.targeting dendritic cells (dc) is key to driving effective immune responses. lymphatic cannulation provides access to the heterogeneous populations of dc draining peripheral sites in rodents and ruminants. afferent lymph dec-205(+)cd11c(+)sirpa(+) dc were preferentially infected ex vivo with three vaccine viral vectors: replication defective human adenovirus-5 (rhuadv5); modified vaccinia virus ankara (rmva) and fowlpox virus (rfpv) all expressing green fluorescent protein (gfp). the rhuadv5 inf ...201121752909
structural basis for the biological relevance of the invariant apical stem in ires-mediated translation.rna structure plays a fundamental role in internal initiation of translation. picornavirus internal ribosome entry site (ires) are long, efficient cis-acting elements that recruit the ribosome to internal mrna sites. however, little is known about long-range constraints determining the ires rna structure. here, we sought to investigate the functional and structural relevance of the invariant apical stem of a picornavirus ires. mutation of this apical stem revealed better performance of g:c compa ...201121742761
understanding foot-and-mouth disease virus early pathogenesis and immune responses. 201121733132
detection of foot-and-mouth disease virus rna in pharyngeal epithelium biopsy samples obtained from infected cattle: investigation of possible sites of virus replication and persistence.foot-and-mouth disease (fmd) is a highly contagious viral infection of significant financial importance to the export and trade of agricultural products. the occurrence of persistently infected "carriers" of fmd-virus (fmdv) in ruminant species adds further complications to disease control. there have been significant discrepancies in reports regarding the pathogenesis of fmdv infection in cattle with specific emphasis on the anatomical sites involved in early and persistent virus replication. i ...201121831538
in-vitro and in-vivo phenotype of type asia 1 foot-and-mouth disease viruses utilizing two non-rgd receptor recognition sites.foot-and-mouth disease virus (fmdv) uses a highly conserved arg-gly-asp (rgd) triplet for attachment to host cells and this motif is believed to be essential for virus viability. previous sequence analyses of the 1d-encoding region of an fmdv field isolate (asia1/js/cha/05) and its two derivatives indicated that two viruses, which contained an arg-asp-asp (rdd) or an arg-ser-asp (rsd) triplet instead of the rgd integrin recognition motif, were generated serendipitously upon short-term evolution ...201121711567
detection of foot-and-mouth disease virus in the breath of infected cattle using a hand-held device to collect aerosols.exhaled air of individual cattle infected experimentally with foot-and-mouth disease virus (fmdv) was sampled to assess the feasibility of a rapid, non-invasive general screening approach for identifying sources of fmdv infection. the air sampler used was a handheld prototype device employing electrostatic particle capture in a microchip chamber of 10-15╬╝l and was shown to effectively capture a high percentage of airborne microorganisms. the particles were eluted subsequently from the chip cham ...201121723882
[foot and mouth disease virus keeps lurking around the corner]. 201121702179
predicting antigenic sites on the foot-and-mouth disease virus capsid of the south african territories (sat) types using virus neutralization data.foot-and-mouth disease virus (fmdv) outer capsid proteins 1b, 1c and 1d contribute to the virus serotype distribution and antigenic variants that exist within each of the seven serotypes. this study presents phylogenetic, genetic and antigenic analyses of south african territories (sat) serotypes prevalent in sub-saharan africa. here, we show that the high levels of genetic diversity in the p1-coding region within the sat serotypes are reflected in the antigenic properties of these viruses and t ...201121697350
a dna vaccine encoding foot-and-mouth disease virus b and t-cell epitopes targeted to class ii swine leukocyte antigens protects pigs against viral challenge.development of efficient and safer vaccines against foot-and-mouth disease virus (fmdv) is a must. previous results obtained in our laboratory have demonstrated that dna vaccines encoding b and t cell epitopes from type c fmdv, efficiently controlled virus replication in mice, while they did not protect against fmdv challenge in pigs, one of the fmdv natural hosts. the main finding of this work is the ability to improve the protection afforded in swine using a new dna-vaccine prototype (pcmv-apc ...201121820470
in silico analysis of ires rnas of foot-and-mouth disease virus and related picornaviruses.foot-and-mouth disease virus (fmdv) uses an internal ribosome entry site (ires), a highly structured segment of its genomic rna, to hijack the translational apparatus of an infected host. computational analysis of 162 type ii picornavirus ires rna sequences yielded secondary structures that included only base pairs supported by comparative or experimental evidence. the deduced helical sections provided the foundation for a hypothetical three-dimensional model of fmdv ires rna. the model was furt ...201121681504
recombinant vp1, an akt inhibitor, suppresses progression of hepatocellular carcinoma by inducing apoptosis and modulation of ccl2 production.the application of viral elements in tumor therapy is one facet of cancer research. recombinant capsid protein vp1 (rvp1) of foot-and-mouth disease virus has previously been demonstrated to induce apoptosis in cancer cell lines. here, we aim to further investigate its apoptotic mechanism and possible anti-metastatic effect in murine models of hepatocellular carcinoma (hcc), one of the most common human cancers worldwide.201121826248
Comparative study of codon substitution patterns in foot-and-mouth disease virus (serotype O).We compared genetic variations in the VP1 gene of foot-and-mouth disease viruses (FMDVs) isolated since 2000 according to the region of the world from. We analyzed relative synonymous codon usage (RSCU) and phylogenetic relationship between geographical regions, and calculated the genetic substitution patterns between Korean isolate and those from other countries. We calculated the ratios of synonymously substituted codons (SSC) to all observed substitutions and developed a new analytical parame ...201121825834
rapid typing of foot-and-mouth disease serotype asia 1 by reverse transcription loop-mediated isothermal amplification.a reverse transcriptase loop-mediated isothermal amplification (rt-lamp) assay was rapidly used to detect serotype asia 1 of foot-and-mouth disease virus (fmdv) within 45 min at 61°c. all fmdv serotype asia 1 reference strains were positive by rt-lamp, while other viruses such as fmdv serotypes o, c, a and classical swine fever virus, swine vesicular disease virus, porcine reproductive and respiratory syndrome virus and japanese encephalitis virus remained negative. furthermore, fmdv sreotype as ...201122040459
introduction of tag epitopes in the inter-aug region of foot and mouth disease virus: effect on the l protein.foot-and-mouth disease virus (fmdv) initiates translation from two in-frame aug codons producing two forms of the leader (l) proteinase, lab (starting at the first aug) and lb (starting at second aug). in a previous study, we have demonstrated that a cdna-derived mutant fmdv (a24-l1123) containing a 57-nucleotide transposon (tn) insertion between the two aug initiation codons (inter-aug region) was completely attenuated in cattle, suggesting that this region is involved in viral pathogenesis. to ...201120849893
outbreak investigations and genetic characterization of foot-and-mouth disease virus in ethiopia in 2008/2009.the study was conducted in three regional states of ethiopia: amhara, oromia, and addis ababa from august 2008 to april 2009 with the objectives of identifying the genetic diversity of serotypes and topotypes in ethiopia, and determining the attack rate and associations of potential risk factors with foot-and-mouth disease (fmd) seropositivity. a total of 496 cattle were clinically and serologically examined for presence of specific lesions and nonstructural protein for fmd, respectively. of whi ...201120717724
the current state of vaccines used in the field for foot and mouth disease virus in china. 201121162615
capsid proteins from field strains of foot-and-mouth disease virus confer a pathogenic phenotype in cattle on an attenuated, cell-culture-adapted virus.chimeric foot-and-mouth disease viruses (fmdvs) have been generated from plasmids containing full-length fmdv cdnas and characterized. the parental virus cdna was derived from the cell-culture-adapted o1kaufbeuren b64 (o1k b64) strain. chimeric viruses, containing capsid coding sequences derived from the o/ukg/34/2001 or a/turkey 2/2006 field viruses, were constructed using the backbone from the o1k b64 cdna, and viable viruses (o1k/o-ukg and o1k/a-tur, respectively) were successfully rescued in ...201121270284
molecular epidemiology of foot-and-mouth disease virus serotypes a and o with emphasis on korean isolates: temporal and spatial dynamics.we determined complete 1d gene sequences for one serotype a and seven additional serotype o korean foot-and-mouth disease viruses (fmdv) and then analyzed them together with published sequences for 180 type a and 300 type o isolates from throughout the world using a bayesian coalescent approach. here, korean serotype a virus was linked with those from laos. korean serotype o viruses were divided into three clades and were closely related to isolates from japan, thailand, the uk, france, ireland, ...201121279395
effects of macromolecular crowding on the inhibition of virus assembly and virus-cell receptor recognition.biological fluids contain a very high total concentration of macromolecules that leads to volume exclusion by one molecule to another. theory and experiment have shown that this condition, termed macromolecular crowding, can have significant effects on molecular recognition. however, the influence of molecular crowding on recognition events involving virus particles, and their inhibition by antiviral compounds, is virtually unexplored. among these processes, capsid self-assembly during viral mor ...201121281589
diagnostic performance and application of two commercial cell viability assays in foot-and-mouth disease research.cell-based assays are still used widely in foot-and-mouth disease (fmd) research, despite the existence of a wide variety of molecular techniques. the aim of this study was to validate an automated, quantitative spectrometric reading to replace the time-consuming and subjective microscopic (mic) evaluation of the fmd virus-induced cytopathic effect (cpe). therefore, the diagnostic performance of two commercial cell viability assays (celltiter 96(®) aqueous one solution cell proliferation assay ( ...201121295609
rescue of foot-and-mouth disease viruses that are pathogenic for cattle from preserved viral rna samples.foot and mouth disease is an economically important disease of cloven-hoofed animals including cattle, sheep and pigs. it is caused by a picornavirus, foot-and-mouth disease virus (fmdv), which has a positive sense rna genome which, when introduced into cells, can initiate virus replication.201121298025
common conformational changes induced in type 2 picornavirus iress by cognate trans-acting factors.type 2 internal ribosomal entry sites (iress) of encephalomyocarditis virus (emcv), foot-and-mouth disease virus (fmdv) and other picornaviruses comprise five major domains h-l. initiation of translation on these iress begins with specific binding of the central domain of initiation factor, eif4g to the j-k domains, which is stimulated by eif4a. eif4g/eif4a then restructure the region of ribosomal attachment on the ires and promote recruitment of ribosomal 43s pre-initiation complexes. in additi ...201121306989
bovine plasmacytoid dendritic cells are the major source of type i interferon in response to foot-and-mouth disease virus in vitro and in vivo.type i interferons (alpha/beta interferons [ifn-a/ß]) are the main innate cytokines that are able to induce a cellular antiviral state, thereby limiting viral replication and disease pathology. plasmacytoid dendritic cells (pdcs) play a crucial role in the control of viral infections, especially in response to viruses that have evolved mechanisms to block the type i ifn signal transduction pathway. using density gradient separation and cell sorting, we have highly enriched a population of bovine ...201121307187
the leader proteinase of foot-and-mouth disease virus negatively regulates the type i interferon pathway by acting as a viral deubiquitinase.the leader proteinase (l(pro)) of foot-and-mouth disease virus (fmdv) is a papain-like proteinase that plays an important role in fmdv pathogenesis. previously, it has been shown that l(pro) is involved in the inhibition of the type i interferon (ifn) response by fmdv. however, the underlying mechanisms remain unclear. here we demonstrate that fmdv lb(pro), a shorter form of l(pro), has deubiquitinating activity. sequence alignment and structural bioinformatics analyses revealed that the catalyt ...201121307201
a replication analysis of foot-and-mouth disease virus in swine lymphoid tissue might indicate a putative carrier stage in pigs.abstract: foot-and-mouth disease virus (fmvd), one of the most contagious viruses of cloven-hoofed animals, may cause a prolonged, asymptomatic but persistent infection in ruminants, named the "carrier state". however, it remains an open question whether this carrier state occurs in pigs. here we present quantitative analyses of the duration of fmdv rna and infectivity in lymphoid and epithelial tissues in experimentally infected pigs with fmdv c-s8c1. the data indicated that although fmdv rna r ...201121314905
dna immunization of pigs with foot-and-mouth disease virus minigenes: from partial protection to disease exacerbation.despite several attempts to design new vaccines, there are as of yet no available alternatives to the conventional fmdv vaccines. here, we present the divergent results obtained in pigs after immunization with two experimental dna vaccines encoding one b and two t cell fmdv epitopes, either expressed alone (pcmv-btt) or fused to a strong signal peptide (pcmv-spbtt). while all pigs vaccinated with pcmv-spbtt showed both a delay in the disease onset and reduced severity of signs and lesions after ...201121315115
effect of thiomersal on dissociation of intact (146s) foot-and-mouth disease virions into 12s particles as assessed by novel elisas specific for either 146s or 12s particles.intact (146s) foot-and-mouth disease virions (fmdvs) can dissociate into specific (12s) viral capsid degradation products. using two single-domain antibody fragments that bind specifically to either 146s or 12s particles we developed two elisas for the quantification of these particles in fmdv antigen preparations used for vaccine manufacturing. only o serotype strains are detected in the 146s specific elisa whereas strains of most serotypes are detected in the 12s specific elisa. however, the 1 ...201121316500
molecular characterization of foot-and-mouth disease virus: implications for disease control in bangladesh.foot-and-mouth disease (fmd) is endemic in bangladesh, and to implement an effective fmd control programme, it is essential to understand the complex epidemiology of the disease. here, we report on the characterization of fmd virus (fmdv) recovered from fmd outbreaks in bangladesh in late 2009. all isolated viruses belonged to the fmdv serotype o. the phylogenetic reconstruction showed that all isolates belonged to the middle east-south asia (me-sa) topotype, but fell into two distinct sublineag ...201121320294
active protein aggregates induced by terminally attached self-assembling peptide elk16 in escherichia coli.in recent years, it has been gradually realized that bacterial inclusion bodies (ibs) could be biologically active. in particular, several proteins including green fluorescent protein, ß-galactosidase, ß-lactamase, alkaline phosphatase, d-amino acid oxidase, polyphosphate kinase 3, maltodextrin phosphorylase, and sialic acid aldolase have been successfully produced as active ibs when fused to an appropriate partner such as the foot-and-mouth disease virus capsid protein vp1, or the human ß-amylo ...201121320350
integrin sub-unit expression in cell cultures used for the diagnosis of foot-and-mouth disease.the ability to propagate foot-and-mouth disease virus (fmdv) plays an important role in laboratory diagnosis and the production of vaccines to control the spread of the disease. many established cell lines suffer from poor sensitivity for isolating virus from field samples. one possible factor that limits sensitivity to fmdv is the lack of expression of surface integrins, the primary class of cell receptor used by fmdv to initiate infection. in this study we have sequenced cdnas encoding these m ...201121329991
genomic comparison of foot-and-mouth disease virus r strain and its chick-passaged attenuated strain.the present study examined the genomic differences between foot-and-mouth disease virus (fmdv) r strain and its attenuated, chick-passaged (r(304)) strain. eleven pairs of primers were used to amplify the complete genome of fmdv r and r(304) by rt-pcr. each fragment was cloned into pmd18-t vector and sequenced. nucleotide analyses showed that the genome encoding regions of r and r(304) strains open reading frame (orf) were both 6966 nucleotides (nt) in length, encoding 2322 amino acids. one hund ...201121330068
a simple and rapid colloidal gold-based immunochromatogarpic strip test for detection of fmdv serotype a.a sandwich format immunochromatographic assay for detecting foot-and-mouth disease virus (fmdv) serotypes was developed. in this rapid test, affinity purified polyclonal antibodies from guinea pigs which were immunized with sucking-mouse adapted fmd virus (a/av88(l) strain) were conjugated to colloidal gold beads and used as the capture antibody, and affinity purified polyclonal antibodies from rabbits which were immunized with cell-culture adapted fmd virus (a/cha/09 strain) were used as detect ...201121331888
experimental evidence for competitive growth advantage of genotype vii over vi: implications for foot-and-mouth disease virus serotype a genotype turnover in nature.in india, systematic genotype replacement has been observed for serotype a foot-and-mouth disease virus. after a decade of co-circulation of genotypes vi and vii, genotype vii emerged as the single dominant genotype since 2001. to derive possible explanations for such epochal evolution dynamics, in vitro intergenotype growth competition experiments involving both co- and superinfection regimes were conducted. coinfection of bhk-21 cells demonstrated abrupt loss in the genotype vi viral load with ...201121338995
a pseudotype baculovirus expressing the capsid protein of foot-and-mouth disease virus and a t-cell immunogen shows enhanced immunogenicity in mice.foot-and-mouth disease (fmd) is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. vaccination is still a major strategy in developing countries to control fmd. currently, inactivated vaccine of fmdv has been used in many countries with limited success and safety concerns. development of a novel effective vaccine is must.201121342530
development and initial results of a low cost, disposable, point-of-care testing device for pathogen detection.development of small footprint, disposable, fast, and inexpensive devices for pathogen detection in the field and clinic would benefit human and veterinary medicine by allowing evidence-based responses to future out breaks. we designed and tested an integrated nucleic acid extraction and amplification device employing a loop-mediated isothermal amplification (lamp) or reverse transcriptase-lamp assay. our system provides a screening tool with polymerase-chain-reaction-level sensitivity and speci ...201121342806
gm-csf and il-2 as adjuvant enhance the immune effect of protein vaccine against foot-and-mouth disease.cytokines as molecular adjuvant play a critical role in differentiation of effector t cell subsets and in determination of the magnitude of the response after vaccination. in this study, we investigated the effects of gm-csf and il-2 as adjuvant on the immune responses of vp1 recombinant protein as a model antigen for foot and mouth disease.201121214955
epidemic and economic impacts of delayed detection of foot-and-mouth disease: a case study of a simulated outbreak in california.the epidemic and economic impacts of foot-and-mouth disease virus (fmdv) spread and control were examined by using epidemic simulation and economic (epinomic) optimization models. the simulated index herd was a ≥2,000 cow dairy located in california. simulated disease spread was limited to california; however, economic impact was assessed throughout the united states and included international trade effects. five index case detection delays were examined, which ranged from 7 to 22 days. the simu ...201121217024
biochemical characterization of enterovirus 71 3d rna polymerase.an unusual enterovirus 71 (ev71) epidemic has begun in china since 2008. ev71 rna polymerases (3d(pol)) showed polymerase activity with an mn(2+). little activity was detected with co(2+), and no activity was detected with mg(2+), ca(2+), cu(2+), ni(2+), cd(2+), or zn(2+). it is a primer-dependent polymerase, and the enzyme functioned with both di- and 10-nucleotide rna primers. dna primer, dt15, increased primer activity, similar to other enterovirus 3d(pol). however, ev71 3d(pol) initiated de ...201121220056
phylogenetic structure of serotype a foot-and-mouth disease virus: global diversity and the indian perspective.global epidemiological analysis is vital for implementing progressive regional foot-and-mouth disease control programmes. here, we have generated vp1 region sequences for 55 indian type a outbreak strains and have included complete vp1 sequences from 46 other countries to obtain a comprehensive global phylogeographical impression. a total of 26 regional genotypes within three continental topotypes, based on a 15% nucleotide divergence cut-off criterion, could be identified. these genotypes corre ...201121228130
evaluation of cross-protection between o1 manisa and o1 campos in cattle vaccinated with foot-and-mouth disease virus vaccine incorporating different payloads of inactivated o1 manisa antigen.serology is used to predict vaccine induced protection against challenge with a heterologous strain of the same serotype of foot-and-mouth disease virus (fmdv). to evaluate the accuracy of such predictions, we compared the protection afforded to cattle vaccinated with the o(1) manisa strain of fmdv against challenge with either a homologous (o(1) manisa) or a heterologous strain (o(1) campos). serology by virus neutralization test (vnt) using o(1) manisa antiserum predicted an acceptable protect ...201121236232
picornavirus non-structural proteins as targets for new anti-virals with broad activity.picornaviridae is one of the largest viral families and is composed of 14 genera, six of which include human pathogens. the best known picornaviruses are enteroviruses (including polio, pv, and rhinoviruses), foot-and-mouth disease virus (fmdv), and hepatitis a virus (hav). although infections often are mild, certain strains may cause pandemic outbreaks accompanied with meningitis and/or paralysis. vaccines are available for pv, hav and fmdv. when the oral vaccines are given to immunocompromised ...201121236302
transmission of swine pathogens: different means, different needs.there seems to be two main types of pathogens that cause diseases in swine: those that are mainly introduced through direct pig contacts, and those that are often, and in some situations mainly introduced by indirect transmission means. in this review, the mange mite (sarcoptes scabiei), toxigenic pasteurella multocida and brachyspira hyodysenteriae will be used as examples of the first type, and foot and mouth disease virus, mycoplasma hyopneumoniae and porcine reproductive and respiratory synd ...201121241537
study on seroprevalence, risk factors, and economic impact of foot-and-mouth disease in borena pastoral and agro-pastoral system, southern ethiopia.cross-sectional serological study and questionnaire survey were conducted in borana pastoral and agro-pastoral area to determine seroprevalence and risk factors associated with foot-and-mouth disease (fmd) infection and to assess community perceptions as to importance of the disease. a multistage random sampling was carried out to select cattle for seroprevalence and households for interviews. totally, 768 sera were collected from 111 herds. the overall individual level seroprevalence of 23.0% ( ...201121249448
influence of mutagenesis and viral load on the sustained low-level replication of an rna virus.lethal mutagenesis is an antiviral strategy that aims to extinguish viruses as a consequence of enhanced mutation rates during virus replication. the molecular mechanisms that underlie virus extinction by mutagenic nucleoside analogues are not well understood. when mutagenic agents and antiviral inhibitors are administered sequentially or in combination, interconnected and often conflicting selective constraints can influence the fate of the virus either towards survival through selection of mut ...201121256131
the expressions of hsp70 and ab-crystallin in myocarditis associated with foot-and-mouth disease virus in lambs.this study describes the expression of heat shock protein70 (hsp70) and alpha-basic-crystallin (a-bc) and their association with apoptosis and some related adaptor proteins in the pathogenesis of foot-and-mouth disease virus (fmdv)-induced myocarditis in lambs. hsp70 was generally overexpressed in the myocardial tissues and inflammatory cells of fmdv-induced myocarditis with differential accumulation and localization in same hearts when compared to non-foot-and-mouth disease control hearts. a-bc ...201121368565
fine mapping of a foot-and-mouth disease virus epitope recognized by serotype-independent monoclonal antibody 4b2.vp2 is a structural protein of the foot-and-mouth disease virus (fmdv). in this study, a fmdv serotype-in-dependent monoclonal antibody (mab), 4b2, was generated. by screening a phage-displayed random 12-peptide library, we found positive phages displaying the consensus motif ettxle (x is any amino acid (aa)), which is highly homologous to (6)ettlle(11) at the n-terminus of the vp2 protein. subsequently, a series of gst-fusion proteins expressing a truncated n-terminus of vp2 were examined by we ...201121369985
rapid and transient activation of +¦+¦ t cells to ifn-+¦ production, nk cell-like killing, and antigen processing during acute virus infection.+¦+¦ t cells are the majority peripheral blood t cells in young cattle. the role of +¦+¦ t cells in innate responses against infection with foot-and-mouth disease virus was analyzed on consecutive 5 d following infection. before infection, bovine wc1(+) +¦+¦ t cells expressed a nonactivated phenotype relative to cd62l, cd45ro, and cd25 expression and did not produce ifn-+¦ ex vivo. additionally, cd335 expression was lacking and no spontaneous target cell lysis could be detected in vitro, althoug ...201121383249
absence of heat intolerance (panting) syndrome in foot-and-mouth disease-affected indian cattle (bos indicus) is associated with intact thyroid gland function.foot-and-mouth disease (fmd) is a highly contagious and economically important viral disease with high morbidity and reduced productivity of affected animals. we studied the heat intolerance (hi) (panting) syndrome and the effect of fmd virus (fmdv) infection on thyroid gland function in indian cattle (bos indicus). experimental infection with fmdv asia 1 resulted in a mild form of disease with superficial lesions. heat intolerance syndrome and its signs were not observed among the recovered ani ...201121388520
development of expression vectors based on pepino mosaic virus. 201121396092
the importance of being short: the role of rabies virus phosphoprotein isoforms assessed by differential ires translation initiation.the rabies virus (rv) phosphoprotein p is a multifunctional protein involved in viral rna synthesis and in counteracting host innate immune responses. we have previously shown that rv p gene expression levels can be regulated by using picornavirus internal ribosome entry site (ires) elements. here we exploited a particular feature of the foot-and-mouth disease virus (fmdv) ires, namely, preferential initiation at a downstream initiation codon, to address the role of n-terminally truncated rv pho ...201121397980
foot-and-mouth disease virus leader proteinase inhibits dsrna-induced rantes transcription in pk-15 cells.the chemokine rantes (regulated upon activation, normal t-cells expressed and secreted) plays an essential role in inflammation and immune response. infection with wild-type foot-and-mouth disease virus (fmdv) in pk-15 cells strongly inhibits the expression of rantes compared to infection with a genetically engineered mutant lacking the leader protein (l(pro)) coding region. this suggests that l(pro) is involved in rantes regulation. however, the underlying molecular mechanism remains unclear. i ...201121399922
establishment of persistent infection with foot-and-mouth disease virus in bhk-21 cells.abstract:201121492421
biosecurity and fmd transmission. 201121493485
isolation, identification and complete genome sequence analysis of a strain of foot-and-mouth disease virus serotype asia1 from pigs in southwest of china.abstract: backgroud: foot-and-mouth disease virus (fmdv) serotype asia1 generally infects cattle and sheep, while its infection of pigs is rarely reported. in 2005-2007, fmd outbreaks caused by asia1 type occurred in many regions of china, as well as some parts of east asia countries. during the outbreaks, there was not any report that pigs were found to be clinically infected. results: in this study, a strain of fmdv that isolated from pigs was identified as serotype asia1, and designated as "a ...201121496298
evidence of activation and suppression during the early immune response to foot-and-mouth disease virus.foot-and-mouth disease virus causes a serious disease of livestock species, threatening free global trade and food security. the disease spreads rapidly between animals, and to ensure a window of opportunity for such spread, the virus has evolved multiple mechanisms to subvert the early immune response. the cycle of infection in the individual animal is very short, infection is initiated, disseminated throughout the body and infectious virus produced in <7 days. foot-and-mouth disease virus has ...201121501424
development and validation of a prokaryotically expressed foot-and-mouth disease virus non-structural protein 2c'3ab-based immunochromatographic strip to differentiate between infected and vaccinated animals.abstract:201121513550
rna structural domains in non-coding regions of foot-and-mouth disease virus genome trigger innate immunity in porcine cells and mice.induction of type i interferons (ifn-α/β) in response to viral infection is a crucial step leading to the antiviral state in the host. viruses produce dsrna during their replication cycle that is sensed as non-self by host cells through different receptors. a signalling cascade is then activated to block viral replication and spread. foot-and-mouth disease virus (fmdv) is a picornavirus, highly sensitive to ifn, causing one of the world's most important animal diseases. in this study, we showed ...201121525336
an experimental infection in pigs using a foot-and-mouth disease virus isolated from the 2010 epidemic in japan.in this study, we carried out an experimental infection in pigs using a foot-and-mouth disease virus isolated from the 2010 epidemic in japan to analyze clinical manifestation, antibody response and virus sedding patterns in pigs. we found that the virus was virulent in pigs, producing a synchronous disease in the inoculated pigs and efficient spread to direct contact pigs. these results are useful for epidemiologically investigating the 2010 epidemic in japan and improving the measures for cont ...201121532260
identification of the role of rig-i, mda-5 and tlr3 in sensing rna viruses in porcine epithelial cells using lentivirus-driven rna interference.pathogen recognition receptors are essential for antiviral host immune responses. these specialized receptors detect conserved viral compounds and induce type i interferons (ifn) and pro-inflammatory cytokines. here we evaluated the contribution of rig-i, mda-5 and tlr3 to the recognition of classical swine fever (csfv), foot-and-mouth disease virus (fmdv), vesicular stomatitis virus (vsv) and influenza a virus (iav) to ifn-β responses in the porcine epithelial cell line pk-15. to this end, we i ...201121539869
development of one-step multiplex rt-pcr method for simultaneous detection and differentiation of foot-and-mouth disease virus serotypes o, a, and asia 1 circulating in vietnam.a one-step multiplex rt-pcr method using new primers was developed for the simultaneous detection and differentiation of vietnamese fmdv serotypes o, a, and asia 1 directly from clinical samples. the rt-pcr method used a cocktail of one universal minus-sense primer designed in the 2b gene and three serotype-specific plus-sense primers designed in the hypervariable regions of the capsid vp1 coding gene of fmdv. these serotype-specific primer pairs amplified 658, 535, and 427bp pcr products corres ...201121550367
relationship between clinical signs and transmission of an infectious disease and the implications for control.control of many infectious diseases relies on the detection of clinical cases and the isolation, removal, or treatment of cases and their contacts. the success of such "reactive" strategies is influenced by the fraction of transmission occurring before signs appear. we performed experimental studies of foot-and-mouth disease transmission in cattle and estimated this fraction at less than half the value expected from detecting virus in body fluids, the standard proxy measure of infectiousness. th ...201121551063
[construction and expression of a coxsackievirus a16 vp1 gene plasmid which delivered by live attenuated salmonella.]aim: to develop a coxsackievirus a16 (cox a16) vp1 gene plasmid which delivered by live attenuated salmonella. methods: the plasmid which expressed vp1 protein of coxa16 was constructed by gene recombination. cellular expression was assessed by western bloten analysis. then the recombinant attenuated salmonella which harboring the plasmid were constructed by electro transformation. results: coxa16 vp1 gene sequence was inserted into a eukaryotic expression plasmid. vp1 protein was detected in th ...201121557905
foot and mouth disease virus polyepitope protein produced in bacteria and plants induces protective immunity in guinea pigs.the goal of this project was to develop an alternative foot and mouth disease (fmd) vaccine candidate based on a recombinant protein consisting of efficient viral epitopes. a recombinant gene was designed that encodes b-cell epitopes of proteins vp1 and vp4 and t-cell epitopes of proteins 2c and 3d. the polyepitope protein (h-pe) was produced in e. coli bacteria or in n. benthamiana plants using a phytovirus expression system. the methods of extraction and purification of h-pe proteins from bact ...201121568869
analysis of the acute phase responses of serum amyloid a, haptoglobin and type 1 interferon in cattle experimentally infected with foot-and-mouth disease virus serotype o.abstract: a series of challenge experiments were performed in order to investigate the acute phase responses to foot-and-mouth disease virus (fmdv) infection in cattle and possible implications for the development of persistently infected "carriers". the host response to infection was investigated through measurements of the concentrations of the acute phase proteins (apps) serum amyloid a (saa) and haptoglobin (hp), as well as the bioactivity of type 1 interferon (ifn) in serum of infected anim ...201121592356
phylogenetic analysis of foot-and-mouth disease virus type o circulating in the andean region of south america during 2002-2008.at present, foot-and-mouth disease (fmd) has been successfully controlled in most territories of south america, where only ecuador and venezuela remain as endemic countries. in this context, the precise characterization of circulating viruses is of utmost importance. this work describes the first molecular epidemiology study performed with the complete vp(1)-coding region of 114 field isolates of fmd virus (fmdv) type o, collected in the andean countries mainly during 2002-2008. sequences were a ...201121601999
control of foot-and-mouth disease. 201121602410
high cleavage efficiency of a 2a peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice.when expression of more than one gene is required in cells, bicistronic or multicistronic expression vectors have been used. among various strategies employed to construct bicistronic or multicistronic vectors, an internal ribosomal entry site (ires) has been widely used. due to the large size and difference in expression levels between genes before and after ires, however, a new strategy was required to replace ires. a self-cleaving 2a peptide could be a good candidate to replace ires because o ...201121602908
comparative complete genome analysis of indian type a foot-and-mouth disease virus field isolates.comparative complete genome analysis of 17 serotype a indian field isolates representing different genotypes and sub-lineages is presented in this report. overall 79% of amino acids were invariant in the coding region. chunk deletion of nucleotide was observed in s and l fragment of 5'-utr. more variability which is comparable to that of capsid coding region was found in l and 3a region. functional motifs and residues critical for virus biology were conserved most. polyprotein cleavage sites acc ...201121604149
[diversity of receptor recognition site of type asial foot-and-mouth disease virus].foot-and-mouth disease virus (fmdv) initiates infection by binding to integrin receptors via a highly conserved arg-gly-asp (rgd) sequence found in the g-h loop of the structural protein vp1. however, fmdv is an rna virus, which harbors the evolutionary potential to render the rgd motif dispensable upon changes in constant environment. we studied mutation of rgd motif upon short-time passages fmdv asial/js/china/2005 field strain in different host.201121604558
the importance of fmdv localisation in lymphoid tissue.foot-and-mouth disease virus, a highly contagious pathogen that can cause lameness, low weight and decreased milk production, is a scourge of agricultural livestock around the world. although the acute phase of infection is rarely fatal, infection may persist in animals that have apparently recovered, creating a viral reservoir that some fear could contribute to the spread of disease. we have used an array of molecular techniques to search for traces of virus in tissues from the mouths and throa ...201121616546
rapid screening swine foot-and-mouth disease virus using micro-elisa system.in order to tackle both regional and global foot-and-mouth disease virus (fmdv) epdimics, we hereby develop a rapid microfluidic thermal lens microscopic method to screen swine type o fmdv with good efficiency. the scheme has great merits in terms of field portability, sample volume, assay time, analytical sensitivity, and test reproducibility.201121617821
multiplex rt-pcr detection and microarray typing of vesicular disease viruses.a vesicular disease multiplex reverse transcription (rt)-pcr with an accompanying microarray assay was developed for simultaneous detection and typing of foot-and-mouth disease virus (fmdv) and vesicular stomatitis virus (vsv), and for the detection of swine vesicular disease virus (svdv) and vesicular exanthema of swine virus (vesv). the multiplex rt-pcr successfully detected viral rna from a collection of 49 strains of vesicular viruses, including multiple strains from all seven serotypes of f ...201121620898
genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle.farm animals remain at risk of endemic, exotic and newly emerging viruses. vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. a complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. however, identification of the causal polymorphisms is not straightforw ...201121621277
[early steps of picornavirus infection].picornaviridae is a large family of viruses that cause a variety of infectious diseases in humans and animals. it includes important viruses such as poliovirus, hepatisis a virus and foot and mouth disease virus. early steps of infection play important roles in determining the host range and the target organs for each virus. here, i review the recent advances in the studies of cellular receptors for picornaviruses, mechanisms of cell entry and viral uncoating.201122916565
bacterial toxin fusion proteins elicit mucosal immunity against a foot-and-mouth disease virus antigen when administered intranasally to guinea pigs.peptides corresponding to the foot-and-mouth disease virus vp1 g-h loop are capable of inducing neutralizing antibodies in some species but are considered relatively poor immunogens, especially at mucosal surfaces. however, intranasal administration of antigens along with the appropriate delivery vehicle/adjuvant has been shown to induce mucosal immune responses, and bacterial enterotoxins have long been known to be effective in this regard. in the current study, two different carrier/adjuvant a ...201122312350
immune response in goats to different payloads of fmdv monovalent vaccine: protection against virulent challenge and development of carrier status.the relationship of foot-and-mouth disease virus antigen payload and number of dose of vaccine conferring protection against virus challenge in goats was studied. goats vaccinated with oil adjuvant foot-and-mouth disease vaccines containing different antigen payloads with or without booster resisted virulent challenge at 21 days post-vaccination or 7 days after booster respectively. however, localized sub-clinical infection was observed in two vaccinated goats on 35 days post-challenge. rna coul ...201122282634
comparison of ires and f2a-based locus-specific multicistronic expression in stable mouse lines.efficient and stoichiometric expression of genes concatenated by bi- or multi-cistronic vectors has become an invaluable tool not only in basic biology to track and visualize proteins in vivo, but also for vaccine development and in the clinics for gene therapy. to adequately compare, in vivo, the effectiveness of two of the currently popular co-expression strategies - the internal ribosome entry site (ires) derived from the picornavirus and the 2a peptide from the foot-and-mouth disease virus ( ...201122216134
detection and genetic characterization of foot-and-mouth disease viruses in samples from clinically healthy animals in endemic settings.a total of 1501 oral swab samples from pakistan, afghanistan and tajikistan were collected from clinically healthy animals between july 2008 and august 2009 and assayed for the presence of foot-and-mouth disease virus (fmdv) rna. the oral swab samples from two (of four) live animal markets in pakistan (n = 245), one (of three) live animal market in afghanistan (n=61) and both the live animal markets in tajikistan (n=120) all tested negative. however, 2 of 129 (∼2%) samples from gondal and 11 of ...201122212855
tissue culture independent transformation of the forage crop sunnhemp (crotalaria juncea l.): an easy method towards generation of transgenics.a transformation system which is free of in vitro plant regeneration following agrobacterium infection is established for the forage legume, sunnhemp (crotalaria juncea l.) where in the entire embryo axis of the germinating seed was used as the target tissue for transformation. after standardization of transformation conditions, the cotyledonary node of the embryo axis was infected with agrobacterium host lba 4404 harboring the recombinant vector pcambia 2301. the bivalent 1d gene of the two maj ...201123573040
self replicating gene vaccine carrying p1-2a gene of fmdv serotype o and its effects on the immune responses of cattle.dna vaccines are considered as alternatives to live attenuated ones for those diseases like foot-and-mouth disease (fmd) where the production and application of live vaccines have been found unsuccessful. however, stability of dna and the quantity of antigen expressed are the major limitation with naked dna vaccines. to address these issues self replicating gene vaccine construct was made for foot-and-mouth disease virus (fmdv) type 'o' and studied. the vector for vaccine construct, designated a ...201123637502
florfenicol impairs the immune responses to vaccination against foot-and-mouth disease in mice.florfenicol is a new type of broad-spectrum antibacterial that has been used in veterinary clinics. it showed immunosuppressive activity on the immune responses to vaccination against foot-and-mouth disease virus (fmdv) serotype o in mice. in the present study, balb/c mice were immunized subcutaneously with fmdv serotype o antigen on days 1 and 14. beginning on day 21, mice were treated with a single daily oral dose of florfenicol (50, 100, and 200?mg/kg) for seven consecutive days. on day 28, b ...201121428714
development of vaccines toward the global control and eradication of foot-and-mouth disease.foot-and-mouth disease (fmd) is one of the most economically and socially devastating diseases affecting animal agriculture throughout the world. although mortality is usually low in adult animals, millions of animals have been killed in efforts to rapidly control and eradicate fmd. the causing virus, fmd virus (fmdv), is a highly variable rna virus occurring in seven serotypes (a, o, c, asia 1, sat 1, sat 2 and sat 3) and a large number of subtypes. fmdv is one of the most infectious agents kno ...201121434805
antiviral activity of bovine type iii interferon against foot-and-mouth disease virus.foot-and-mouth disease (fmd) is one of the most serious threats to the livestock industry. despite the availability of a vaccine, recent outbreaks in disease-free countries have demonstrated that development of novel fmd control strategies is imperative. here we report the identification and characterization of bovine (bo) interferon lambda 3 (ifn-++3), a member of the type iii ifn family. expression of boifn-++3 using a replication-defective human adenovirus type 5 vector (ad5-boifn-++3) yielde ...201121435672
viral genome segmentation can result from a trade-off between genetic content and particle stability.the evolutionary benefit of viral genome segmentation is a classical, yet unsolved question in evolutionary biology and rna genetics. theoretical studies anticipated that replication of shorter rna segments could provide a replicative advantage over standard size genomes. however, this question has remained elusive to experimentalists because of the lack of a proper viral model system. here we present a study with a stable segmented bipartite rna virus and its ancestor non-segmented counterpart, ...201121437265
phylogenomics and molecular evolution of foot-and-mouth disease virus.this report describes the use of bayesian methods to analyze polyprotein coding region sequences (n = 217) obtained from genbank to define the genome-wide phylogeny of foot and mouth disease virus (fmdv). the results strongly supported the monophyly of five fmdv serotypes, o, a, asia 1, c, and sat 3, while sequences for the two remaining fmdv serotypes, sat 1 and sat 2 did not separate into entirely distinct clades. the phylogenomic tree revealed three sister-group relationships, serotype o + as ...201121448588
skin as a potential source of infectious foot and mouth disease aerosols.this review examines whether exfoliated, virus-infected animal skin cells could be an important source of infectious foot and mouth disease virus (fmdv) aerosols. infectious material rafting on skin cell aerosols is an established means of transmitting other diseases. the evidence for a similar mechanism for fmdv is: (i) fmdv is trophic for animal skin and fmdv epidermis titres are high, even in macroscopically normal skin; (ii) estimates for fmdv skin cell aerosol emissions appear consistent wi ...201121450741
a highly sensitive detection for foot-and-mouth disease virus by gold nanopariticle improved immuno-pcr.abstract: background: foot-and-mouth disease (fmd) is one of the most contagious of all artiodactyl animal diseases, and its infection has an obvious ability to spread over long distances and to contribute to epidemics in fmd-free areas. a highly sensitive and specfic method is required to detect fmdv. in this study, we evaluated the usefulness of a bio-barcode assay (bca) technique for detecting clinical samples of fmdv. methods: highly sensitive gold nanopariticle (gnp) improved immuno -pcr (g ...201121453461
viewpoint: factors involved in type i interferon responses during porcine virus infections.since type i interferon (ifn-i) is considered a potent antiviral defence mechanism, it is not surprising that during evolution viruses have development of various mechanisms to counteract ifn-i induction or release. despite this, certain virus infections are associated with very high levels of systemic ifn-i. one explanation for this observation is the presence of plasmacytoid dendritic cells (pdc), which are able to produce high levels of ifn-i despite the presence of viral ifn-i antagonists. e ...201121458079
differentiation of foot-and-mouth disease-infected pigs from vaccinated pigs using antibody-detecting sandwich elisa.the presence of serum antibodies for nonstructural proteins of the foot-and-mouth disease virus (fmdv) can differentiate fmdv-infected animals from vaccinated animals. in this study, a sandwich elisa was developed for rapid detection of the foot-and-mouth disease (fmd) antibodies; it was based on an escherichia coli-expressed, highly conserved region of the 3abc nonstructural protein of the fmdv o/tw/99 strain and a monoclonal antibody derived from the expressed protein. the diagnostic sensitivi ...201121467761
closed ampoule isothermal microcalorimetry for continuous real-time detection and evaluation of cultured mammalian cell activity and responses.closed ampoule isothermal microcalorimetry (imc) is a simple, powerful, nondestructive, and convenient technique that allows continuous, real-time detection and evaluation of cultured cell activity and responses. at a selected set temperature, imc measures the heat flow between a sample and a heat sink and compares it to the heat-flow between a thermally inactive reference and the heat sink. since heat flow rates are proportional to the rates of chemical reactions and changes of state, imc provi ...201121468980
comparative sequence analysis of representative foot-and-mouth disease virus genomes from southeast asia.foot-and-mouth disease (fmd) is endemic in mainland southeast asia where up to seven genetically distinct viral lineages co-circulate (o/sea/mya-98, o/sea/cam-94, o/me-sa/panasia, o/me-sa/panasia-2, o/cathay, a/asia/sea-97, and serotype asia 1). the aim of this study was to analyse the sequence variability between representative complete genomes for these seven lineages. the genome sequences varied from 8130 to 8192 nucleotides in length and shared nucleotide identities ranging from 91.8 to 78.9 ...201121479678
foot-and-mouth disease in feral swine: susceptibility and transmission.experimental studies of foot-and-mouth disease (fmd) in feral swine are limited, and data for clinical manifestations and disease transmissibility are lacking. in this report, feral and domestic swine were experimentally infected with fmdv (a24-cruzeiro), and susceptibility and virus transmission were studied. feral swine were proved to be highly susceptible to a-24 cruzeiro fmd virus by intradermal inoculation and by contact with infected domestic and feral swine. typical clinical signs in fera ...201121418546
pan-serotypic detection of foot-and-mouth disease virus using a minor groove binder probe reverse transcription polymerase chain reaction assay.a novel assay for the pan-serotypic detection of foot-and-mouth disease virus (fmdv) was designed using a 5' conjugated minor groove binder (mgb) probe real-time rt-pcr system. this assay targets the 3d region of the fmdv genome and is capable of detecting 20 copies of a transcribed rna standard. the linear range of the test was eight logs from 2 × 10¹ to 2 × 108 copies and amplification time was approximately 2 h. using a panel of 83 rna samples from representative fmdv isolates, the diagnostic ...201121419170
genetic diversity of foot-and-mouth disease virus serotype o in pakistan and afghanistan, 1997-2009.foot-and-mouth disease (fmd) is endemic in pakistan and afghanistan; serotypes o, a and asia-1 of the virus are responsible for the outbreaks in these countries with fmdv type o usually being the most common. in the present study, the nucleotide sequences encoding the fmdv capsid protein vp1 from virus samples were determined. phylogenetic analysis of the serotype o fmd viruses circulating in pakistan and afghanistan between 1997 and 2009 revealed the presence of at least three different lineage ...201121419880
Tempo and mode of inhibitor-mutagen antiviral therapies: a multidisciplinary approach.The continuous emergence of drug-resistant viruses is a major obstacle for the successful treatment of viral infections, thus representing a persistent spur to the search for new therapeutic strategies. Among them, multidrug treatments are currently at the forefront of pharmaceutical, clinical, and computational investigation. Still, there are many unknowns in the way that different drugs interact among themselves and with the pathogen that they aim to control. Inspired by experimental studies w ...201121911373
Establishment of a Stable Cell Line Coexpressing Dengue Virus-2 and Green Fluorescent Protein for Screening of Antiviral Compounds.This study aimed to generate a stable cell line harboring subgenomic dengue virus replicon and a green fluorescent gene (DENV/GFP) for a cell-based model to screen anti-DENV compounds. The gene-encoding envelope protein of DENV-2 was deleted and then replaced with fragments of the GFP gene and a foot-and-mouth-disease virus 2A-derived cleavage site. The human cytomegalovirus immediate early and antisense hepatitis delta virus ribozyme sequences were added at the 5'- and 3'-ends. An internal ribo ...201122068705
increased efficacy of an adenovirus-vectored foot-and-mouth disease capsid subunit vaccine expressing nonstructural protein 2b is associated with a specific t cell response.we previously demonstrated that an adenovirus-based foot-and-mouth disease virus (fmdv) serotype a24 capsid subunit vaccine, ad5-a24, expressed under the control of a cytomegalovirus promoter (cmv) can protect swine and bovines against homologous challenge, but in a similar approach using swine vaccinated with an ad5-vectored fmdv o1 campos vaccine, ad5-o1c, the animals were only partially protected when challenged at 21 days post-vaccination (dpv). recently, we demonstrated that inclusion of th ...201122027486
Formation of higher-order FMDV 3Dpol complexes is dependent on elongation activity.The replication of many viruses involves the formation of higher-order structures or replication 'factories'. We show that the key replication enzyme of foot-and-mouth disease virus (FMDV), the RNA-dependent-RNA polymerase, forms fibrils in vitro. Although there are similarities with previously characterised poliovirus polymerase fibrils, FMDV fibrils are narrower, composed of both protein and RNA and, importantly, are only seen when all components of an elongation assay are present. Furthermore ...201122156531
Investigation of serum protein profiles in sheep naturally infected with foot-and-mouth disease virus.This study was carried out to determine serum protein profiles in naturally infected sheep with foot-and-mouth disease virus (FMDV). The study material consisted of twelve healthy and 36 sheep with foot-and-mouth disease (FMD). FMD had been diagnosed on the basis of clinical findings and results of serological examination. Serotypes serologically detected in the FMDV-infected sheep were as follows: O (n = 11), A (n = 8) and mixed infection with serotypes O, A and Asia-1 (n = 17).The total protei ...201122059288
virus survival in slurry: analysis of the stability of foot-and-mouth disease, classical swine fever, bovine viral diarrhoea and swine influenza viruses.farm slurry can be highly contaminated with viral pathogens. the survival of these pathogens within slurry is important since this material is often distributed onto farm land either directly or after heat treatment. there is clearly some risk of spreading pathogens in the early stages of an outbreak of disease before it has been recognized. the survival of foot-and-mouth disease virus, classical swine fever virus, bovine viral diarrhoea virus and swine influenza virus, which belong to three dif ...201122226541
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