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novel antibody binding determinants on the capsid surface of serotype o foot-and-mouth disease virus.five neutralizing antigenic sites have been described for serotype o foot-and-mouth disease viruses (fmdv) based on monoclonal antibody (mab) escape mutant studies. however, a mutant virus selected to escape neutralization of mab binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mab binding sites contribute to antibody-mediated in vivo neutralization of fmdv. ...201424584474
the expression of il6 and 21 in crossbred calves upregulated by inactivated trivalent fmd vaccine.foot and mouth disease (fmd) is an economically important disease and a whole-virus inactivated trivalent virus vaccine is the mainstay for controlling the disease in india. the protective humoral immune response to fmd vaccination is a complex, but, tightly regulated process mediated by the interplay of interleukins (il). based on the specific role of il6 and 21 in adaptive immune response, we hypothesized that inactivated trivalent fmd vaccine would stimulate il6 and 21 expression in the circu ...201424555796
infection dynamics of foot-and-mouth disease virus in pigs using two novel simulated-natural inoculation methods.in order to characterize foot-and-mouth disease virus (fmdv) infection dynamics in pigs, two simulated-natural inoculation systems were developed and evaluated. intra-oropharyngeal (iop) and intra-nasopharyngeal (inp) inoculation both enabled precise control of dose and timing of inoculation while simulating field exposure conditions. there were substantial differences between outcomes of infections by the two routes. iop inoculation resulted in consistent and synchronous infection, whereas inp ...201424548596
neutralizing antibody responses to foot-and-mouth disease quadrivalent (type o, a, c and asia 1) vaccines in growing calves with pre-existing maternal antibodies.the presence of maternal antibodies is a major obstacle for eliciting protective immune responses to foot-and-mouth disease (fmd) vaccines in young, growing animals. in this report, we analyzed the ability of inactivated quadrivalent oil emulsified and aluminium hydroxide adjuvanted fmd vaccines to elicit neutralizing antibody responses in growing calves that had maternal antibodies. our results demonstrate that oil emulsified vaccines but not aluminium hydroxide adjuvanted fmd vaccines could su ...201424508311
complete genome sequence of foot-and-mouth disease virus serotype o isolated from bangladesh.foot-and-mouth disease (fmd) is a highly infectious enzootic disease caused by fmd virus. the complete genome sequence of a circulatory fmd virus (fmdv) serotype o isolated from natore, bangladesh, is reported here. genomic analysis revealed antigenic heterogeneity within the vp1 region, a fragment deletion, and insertions at the 5' untranslated region (utr) and 3a region compared to the genome of the available vaccine strain.201424503997
a recombinant adenovirus bicistronically expressing porcine interferon-α and interferon-γ enhances antiviral effects against foot-and-mouth disease virus.foot-and-mouth disease (fmd) is a virulent and economically costly disease in domestic livestock. since the current vaccine available against fmd provides no protection until 7days postvaccination, the only alternative method to halt the spread of the fmd virus (fmdv) during outbreaks is by the application of anti-viral agents. the combination of recombinant adenovirus expressing type i interferon (ifn-α) and adenovirus expressing type ii ifn (ifn-γ) has been reported to be an effective anti-vir ...201424485895
immunogenicity of the capsid precursor and a nine-amino-acid site-directed mutant of the 3c protease of foot-and-mouth disease virus coexpressed by a recombinant goatpox virus.the myristoylated capsid precursor mp1-2a of foot-and-mouth disease virus (fmdv), when expressed in mammalian cells and processed by the fmdv 3c protease, can self-assemble into virus-like particles (vlps). in the present study, nine amino acids of the 3c protease were replaced by site-directed mutagenesis to create a mutant 3c protease, 9m3c. to coexpress mp1-2a and 9m3c and test the resulting proteolytic processing and vlp assembly, two recombinant goatpox viruses (rgtpvs) were constructed by ...201424473707
interconversion between parallel and antiparallel conformations of a 4h rna junction in domain 3 of foot-and-mouth disease virus ires captured by dynamics simulations.rna junctions are common secondary structural elements present in a wide range of rna species. they play crucial roles in directing the overall folding of rna molecules as well as in a variety of biological functions. in particular, there has been great interest in the dynamics of rna junctions, including conformational pathways of fully base-paired 4-way (4h) rna junctions. in such constructs, all nucleotides participate in one of the four double-stranded stem regions, with no connecting loops. ...201424461020
induction of protective immune response against both pprv and fmdv by a novel recombinant pprv expressing fmdv vp1.peste des petits ruminants (ppr) and foot-and-mouth disease (fmd) are both highly contagious diseases of small domestic and wild ruminants caused by the ppr virus (pprv) and the fmd virus (fmdv). in this study, a recombinant pprv expressing the fmdv vp1 gene (rpprv/vp1) was generated and fmdv vp1 expression did not impair replication of the recombinant virus in vitro and immunogenicity in inducing neutralizing antibody against ppr in goats. vaccination with one dose of rpprv/vp1 induced fmdv neu ...201424898430
foot-and-mouth disease virus low-fidelity polymerase mutants are attenuated.previous studies have shown that rna viruses can be attenuated by either increased or decreased viral polymerase replication fidelity. although foot-and-mouth disease virus (fmdv) high-fidelity rna-dependent rna polymerase (rdrp) variants with an attenuated phenotype have been isolated using mutagens, no fmdv mutant with a low-fidelity polymerase has been documented to date. here, we describe the generation of several fmdv rdrp mutants using site-directed mutagenesis via a reverse genetic system ...201424888311
estimation of the transmission of foot-and-mouth disease virus from infected sheep to cattle.the quantitative role of sheep in the transmission of foot-and-mouth disease virus (fmdv) is not well known. to estimate the role of sheep in the transmission of fmdv, a direct contact transmission experiment with 10 groups of animals each consisting of 2 infected lambs and 1 contact calf was performed. secretions and excretions (oral swabs, blood, urine, faeces and probang samples) from all animals were tested for the presence of fmdv by virus isolation (vi) and/or rt-pcr. serum was tested for ...201424886222
evaluation of a 3a-truncated foot-and-mouth disease virus in pigs for its potential as a marker vaccine.foot-and-mouth disease (fmd) is a highly contagious and economically devastating disease of cloven-hoofed animals in the world. the disease can be effectively controlled by vaccination of susceptible animals with the conventional inactivated vaccine. however, one major concern of the inactivated fmd virus (fmdv) vaccine is that it does not allow serological discrimination between infected and vaccinated animals, and therefore interferes with serologic surveillance and the epidemiology of disease ...201424885414
the use of an adeno-associated viral vector for efficient bicistronic expression of two genes in the central nervous system.recombinant adeno-associated viral (aav) vectors are one of the most promising therapeutic delivery systems for gene therapy to the central nervous system (cns). preclinical testing of novel gene therapies requires the careful design and production of aav vectors and their successful application in a model of cns injury. one major limitation of aav vectors is their limited packaging capacity (<5 kb) making the co-expression of two genes (e.g., from two promoters) difficult. an internal ribosomal ...201424838969
transmission of foot-and-mouth disease virus from experimentally infected indian buffalo (bubalus bubalis) to in-contact naïve and vaccinated indian buffalo and cattle.this study investigated the transmission of foot-and-mouth disease virus (fmdv) from experimentally infected indian buffalo to in-contact naïve and vaccinated cattle and buffalo. in each of six rooms, two donor buffalo that had been inoculated with fmdv were housed for five days with four recipient animals, comprising one vaccinated buffalo, one vaccinated calf, one unvaccinated buffalo and one unvaccinated calf. vaccination was carried out with current indian vaccine strain (o/ind/r2/75) and ch ...201424837776
determining the epitope dominance on the capsid of a serotype sat2 foot-and-mouth disease virus by mutational analyses.monoclonal-antibody (mab)-resistant mutants were used to map antigenic sites on foot-and-mouth disease virus (fmdv), which resulted in the identification of neutralizing epitopes in the flexible βg-βh loop in vp1. for fmdv sat2 viruses, studies have shown that at least two antigenic sites exist. by use of an infectious sat2 cdna clone, 10 structurally exposed and highly variable loops were identified as putative antigenic sites on the vp1, vp2, and vp3 capsid proteins of sat2/zimbabwe (zim)/7/83 ...201424829347
cpg odn nanorings induce ifnα from plasmacytoid dendritic cells and demonstrate potent vaccine adjuvant activity.cpg oligodeoxynucleotides (odn) are short single-stranded synthetic dna molecules that activate the immune system and have been found to be effective for preventing and treating infectious diseases, allergies, and cancers. structurally distinct classes of synthetic odn expressing cpg motifs differentially activate human immune cells. k-type odn (k-odn), which have progressed into human clinical trials as vaccine adjuvants and immunotherapeutic agents, are strong activators of b cells and trigger ...201424807558
orientation of llama antibodies strongly increases sensitivity of biosensors.sensitivity of biosensors depends on the orientation of bio-receptors on the sensor surface. the objective of this study was to organize bio-receptors on surfaces in a way that their analyte binding site is exposed to the analyte solution. vhh proteins recognizing foot-and-mouth disease virus (fmdv) were used for making biosensors, and azides were introduced in the vhh to function as bioorthogonal reactive groups. the importance of the orientation of bio-receptors was addressed by comparing sens ...201424793095
diagnostic potential of recombinant nonstructural protein 3b to detect antibodies induced by foot-and-mouth disease virus infection in bovines.detection of antibodies to nonstructural proteins (nsp) of foot-and-mouth disease virus is the preferred diagnostic method to differentiate infected from vaccinated animals. in india, an endemic region practising preventive biannual vaccination, 3ab3 indirect elisa (r3ab3 i-elisa) has been employed as the primary screening test for serosurveillance. however, because of the variability observed in the immune response to the nsps, the likelihood of detecting or confirming an infected animal is inc ...201424777827
exploration of sequence space as the basis of viral rna genome segmentation.the mechanisms of viral rna genome segmentation are unknown. on extensive passage of foot-and-mouth disease virus in baby hamster kidney-21 cells, the virus accumulated multiple point mutations and underwent a transition akin to genome segmentation. the standard single rna genome molecule was replaced by genomes harboring internal in-frame deletions affecting the l- or capsid-coding region. these genomes were infectious and killed cells by complementation. here we show that the point mutations i ...201424757055
single amino acid substitution of vp1 n17d or vp2 h145y confers acid-resistant phenotype of type asia1 foot-and-mouth disease virus.infection by foot-and-mouth disease virus (fmdv) is triggered by the acidic ph in endosomes after virus uptake by receptor-mediated endocytosis. however, dissociation of the fmdv 146s particle in mildly acidic conditions renders inactivated foot-and-mouth disease (fmd) vaccines much less effective. type asia1 fmdv mutants with increased resistance to acid inactivation were selected to study the molecular basis of viral resistance to acid-induced disassembly and improve the acid stability of fmdv ...201424752763
molecular biological characteristics of foot-and-mouth disease virus in the african buffalo in southern africa. 201428235272
spatial and temporal distribution of foot-and-mouth disease virus in the eastern zone of tanzania. 201428235270
the changing landscape of the molecular epidemiology of foot-and-mouth disease virus in southern africa north of limpopo and east africa. 201428235269
full genome sequencing to study the evolutionary characteristics of foot-and-mouth disease virus in southern africa. 201428235268
screening for foot-and-mouth disease virus in livestock-wildlife interface areas of tanzania. 201428235267
evaluation of monoclonal antibody-based sandwich direct elisa (msd-elisa) for antigen detection of foot-and-mouth disease virus using clinical samples.a monoclonal antibody-based sandwich direct elisa (msd-elisa) method was previously developed for foot-and-mouth disease (fmd) viral antigen detection. here we evaluated the sensitivity and specificity of two fmd viral antigen detection msd-elisas and compared them with conventional indirect sandwich (is)-elisa. the msd-elisas were able to detect the antigen in saliva samples of experimentally-infected pigs for a longer term compared to the is-elisa. we also used 178 rt-pcr-positive field sample ...201424736560
selection and characterization of an acid-resistant mutant of serotype o foot-and-mouth disease virus.foot-and-mouth disease virus (fmdv) loses infectivity and immunogenicity due to its disassembly in culture environments below ph 6.8. to study the molecular basis of viral resistance to acid-induced disassembly and improve the acid stability of inactivated fmd vaccines during the manufacturing process, type o fmdv mutants with increased resistance to acid inactivation were selected, and the genes encoding their capsid proteins were sequenced. three amino acid substitutions (vp1 n17d, vp2 d86a, a ...201424122111
molecular differentiation and phylogenetic analysis of the egyptian foot-and-mouth disease virus sat2.in february 2012, a massive new foot-and-mouth disease (fmd) outbreak struck egypt. in this work, one-step rt-pcr assays were used for in-house detection and differentiation of foot-and-mouth disease virus (fmdv) in egypt in this year using pan-serotypic and serotype-targeting sequence primers. fmdv sat2 was the dominant virus in the examined isolates from the epidemic. the complete vp1 coding regions of two isolates were sequenced. the two isolates had 99.2 % sequence identity to most contempor ...201424046086
genetic engineering and chemical conjugation of potato virus x.here we report the genetic engineering and chemical modification of potato virus x (pvx) for the presentation of various peptides, proteins, and fluorescent dyes, or other chemical modifiers. three different ways of genetic engineering are described and by these means, peptides are successfully expressed not only when the foot and mouth disease virus (fmdv) 2a sequence or a flexible glycine-serine linker is included, but also when the peptide is fused directly to the pvx coat protein. when large ...201424243237
efficient rescue of foot-and-mouth disease virus in cultured cells transfected with rna extracted from clinical samples.in this study, an rna transfection was used to rescue infectious foot-and-mouth disease (fmd) virus from clinical samples in bhk-21 cell line for diagnosis of fmd. tissue samples (n=190) were subjected to fmd virus isolation by conventional cell culture and also by rna transfection. fmd virus was isolated from 62% of the clinical samples by rna transfection, whereas virus was isolated only from 16% of the clinical samples in conventional cell culture method, suggesting better performance of the ...201424239633
genetic heterogeneity in the leader and p1-coding regions of foot-and-mouth disease virus serotypes a and o in africa.genetic information regarding the leader (l) and complete capsid-coding (p1) region of fmd serotype a and o viruses prevalent on the african continent is lacking. here, we present the complete l-p1 sequences for eight serotype a and nine serotype o viruses recovered from fmdv outbreaks in east and west africa over the last 33 years. phylogenetic analysis of the p1 and capsid-coding regions revealed that the african isolates grouped according to serotype, and certain clusters were indicative of t ...201424221247
antigenic variation of foot-and-mouth disease virus serotype a.the current measures to control foot-and-mouth disease (fmd) include vaccination, movement control and slaughter of infected or susceptible animals. one of the difficulties in controlling fmd by vaccination arises due to the substantial diversity found among the seven serotypes of fmd virus (fmdv) and the strains within these serotypes. therefore, vaccination using a single vaccine strain may not fully cross-protect against all strains within that serotype, and therefore selection of appropriate ...201424187014
identification of factors associated with increased excretion of foot-and-mouth disease virus.we investigated which variables possibly influence the amount of foot-and-mouth disease virus (fmdv) shed in secretions and excretions by fmdv infected animals, as it is likely that the amount of fmdv shed is related to transmission risk. first, in a separate analysis of laboratory data, we showed that the total amount of fmdv in secretions and excretions from infected animals is highly correlated with maximum titres of fmdv. next, we collected data from 32 published scientific articles in which ...201424182985
efficient foreign gene expression in planta using a plantago asiatica mosaic virus-based vector achieved by the strong rna-silencing suppressor activity of tgbp1.plant virus expression vectors provide a powerful tool for basic research as well as for practical applications. here, we report the construction of an expression vector based on plantago asiatica mosaic virus (plamv), a member of the genus potexvirus. modification of a vector to enhance the expression of a foreign gene, combined with the use of the foot-and-mouth disease virus 2a peptide, allowed efficient expression of the foreign gene in two model plant species, arabidopsis thaliana and nicot ...201424154949
molecular modeling and analysis of hepatitis e virus (hev) papain-like cysteine protease.the biochemical or biophysical characterization of a papain-like cysteine protease in hev orf1-encoded polyprotein still remains elusive. very recently, we have demonstrated the indispensability of orf1 protease-domain cysteines and histidines in hev replication, ex vivo (parvez, 2013). in this report, the polyprotein partial sequences of hev strains and genetically-related rna viruses were analyzed, in silico. employing the consensus-prediction results of rubv-p(150) protease as structural-temp ...201424321124
enhanced ires activity by the 3'utr element determines the virulence of fmdv isolates.a reverse genetics approach was used to identify viral genetic determinants of the differential virulence displayed by two field foot-and-mouth disease virus (fmdv) strains (a/arg/00 and a/arg/01) isolated in argentina during the 2000-2001 epidemics. a molecular clone of a/arg/01 strain and viral chimeras containing the s-fragment or the internal ribosome entry site (ires) of a/arg/00 in the a/arg/01 backbone were constructed and characterized. the ires appeared as a determining factor of the lo ...201424314661
an increase in acid resistance of foot-and-mouth disease virus capsid is mediated by a tyrosine replacement of the vp2 histidine previously associated with vp0 cleavage.the foot-and-mouth disease virus (fmdv) capsid is highly acid labile, but introduction of amino acid replacements, including an n17d change in vp1, can increase its acid resistance. using mutant vp1 n17d as a starting point, we isolated a virus with higher acid resistance carrying an additional replacement, vp2 h145y, in a residue highly conserved among picornaviruses, which has been proposed to be responsible for vp0 cleavage. this mutant provides an example of the multifunctionality of picorna ...201424352460
interaction of foot-and-mouth disease virus nonstructural protein 3a with host protein dctn3 is important for viral virulence in cattle.nonstructural protein 3a of foot-and-mouth disease virus (fmdv) is a partially conserved protein of 153 amino acids in most fmdvs examined to date. the role of 3a in virus growth and virulence within the natural host is not well understood. using a yeast two-hybrid approach, we identified cellular protein dctn3 as a specific host binding partner for 3a. dctn3 is a subunit of the dynactin complex, a cofactor for dynein, a motor protein. the dynactin-dynein duplex has been implicated in several su ...201424352458
evaluation of cross-protection against three topotypes of serotype o foot-and-mouth disease virus in pigs vaccinated with multi-epitope protein vaccine incorporated with poly(i:c).epitope-based vaccines are always questioned for their cross-protection against the antigenically variable foot-and-mouth disease virus (fmdv). in this study, we proved the cross-protection effect of a multi-epitope vaccine incorporated with poly(i:c) against three topotypes of o type fmdv. a total of 45 naïve pigs were vaccinated with different doses of multi-epitope protein vaccine incorporated with poly(i:c). at 28 days post-vaccination, 45 vaccinated and 6 unvaccinated control pigs (two pigs ...201424345411
accuracy of traditional and novel serology tests for predicting cross-protection in foot-and-mouth disease vaccinated cattle.foot-and-mouth disease virus (fmdv) antigenic-match between vaccine and field viruses has traditionally been estimated in vitro by computing the r1 value using virus neutralization test (vnt) or elisa titers. in this study we compared the accuracy in predicting cross-protection between the r1 value estimated by vnt and two recently developed tests that measure igg subtypes and avidity. data analyzed consisted of 64 serum samples from fmdv a24/cruzeiro vaccinated bovines challenged with the heter ...201424342253
evolution of serotype a foot-and-mouth disease virus capsid under neutralizing antibody pressure in vitro.in this study, the indian foot-and-mouth disease virus (fmdv) vaccine strain (a ind 40/2000) was passaged under homologous bovine convalescent serum (bcs) pressure to gain insight into the evolutionary dynamics of the antigenic sites. a considerable drop in the neutralization titres of the bcs for the isolated variants as compared to the parental population in either virus neutralization or plaque reduction neutralization test was observed. t143k substitution preceding the integrin binding 'rgd' ...201424452141
a serological survey for antibodies against foot-and-mouth disease virus (fmdv) in domestic pigs during outbreaks in kenya.foot-and-mouth disease (fmd) is endemic in kenya and has been well studied in cattle, but not in pigs, yet the role of pigs is recognised in fmd-free areas. this study investigated the presence of antibodies against fmd virus (fmdv) in pigs sampled during a countrywide random survey for fmd in cattle coinciding with sat 1 fmdv outbreaks in cattle. a total of 191 serum samples were collected from clinically healthy pigs in 17 districts. forty-two of the 191 sera were from pigs vaccinated against ...201424442573
characteristics of a foot-and-mouth disease virus with a partial vp1 g-h loop deletion in experimentally infected cattle.previous work in cattle illustrated the protective efficacy and negative marker potential of a a serotype foot-and-mouth disease virus (fmdv) vaccine prepared from a virus lacking a significant portion of the vp1 g-h loop (termed a(-)). since this deletion also includes the arginine-glycine-aspartate (rgd) motif required for virus attachment to the host cell in vivo, it was hypothesised that this virus would be attentuated in naturally susceptible animals. the a(-) virus was passaged three times ...201424438986
development of porcine respiratory and reproductive syndrome virus replicon vector for foot-and-mouth disease vaccine.foot-and-mouth disease (fmd) is an economically important global animal disease. to control fmd virus (fmdv) outbreaks, a lot of different novel approaches have been attempted. in this study, we proposed a novel porcine reproductive and respiratory syndrome virus (prrsv) as a replicon vector to express fmdv structural protein.201424427767
detection of antibodies specific for foot-and-mouth disease virus infection using indirect elisa based on recombinant nonstructural protein 2b.foot-and-mouth disease (fmd) is a highly contagious viral disease of transboundary importance. in india, since the launch of the fmd control programme, there has been a substantial increase in the vaccinated bovine population. in this scenario, there is a need for additional locally developed non-structural protein (nsp)-based immnoassays for efficient identification of fmd virus (fmdv)-infected animals in the vaccinated population. the 2b nsp of fmdv, lacking the transmembrane domain (δ2b), was ...201424420160
artificial micrornas as antiviral strategy to fmdv: structural implications of target selection.rna interference (rnai) appears as a promising strategy to control virus replication. while the antiviral power of short-hairpin rnas or small-interfering rnas against fmdv has been demonstrated widely, safer rnai effectors such as artificial micrornas (amirs) have not been evaluated extensively. in this work, transgenic monoclonal cell lines constitutively expressing different amirs targeting fmdv 3d-coding region or 3'utr were established. certain cell lines showed an effective, sequence-speci ...201424406623
application of a cell-based protease assay for testing inhibitors of picornavirus 3c proteases.proteolytical cleavage of the picornaviral polyprotein is essential for viral replication. therefore, viral proteases are attractive targets for anti-viral therapy. most assays available for testing proteolytical activity of proteases are performed in vitro, using heterologously expressed proteases and peptide substrates. to deal with the disadvantages associated with in vitro assays, we modified a cell-based protease assay for picornavirus proteases. the assay is based on the induction of expre ...201424393668
detection and seroprevalence of foot and mouth disease in sheep and goats in punjab, pakistan.foot and mouth disease (fmd) is a highly contagious disease of ruminants that causes huge economic losses around the globe. however, the prevalence of fmdv in small ruminants has been overlooked in pakistan. a seroepidemiological study was conducted in chakwal, faisalabad and khanewal districts of punjab, pakistan to determine the prevalence of fmd in sheep and goats. a total 1200 serum samples were collected from sheep (n = 180) and goats (n = 920) and were subjected to 3abc non-structural prot ...201424393420
multiple micrornas targeted to internal ribosome entry site against foot-and-mouth disease virus infection in vitro and in vivo.foot-and-mouth disease virus (fmdv) causes a severe vesicular disease in domestic and wild cloven-hoofed animals. because of the limited early protection induced by current vaccines, emergency antiviral strategies to control the rapid spread of fmd outbreaks are needed.here we constructed multiple micrornas (mirnas) targeting the internal ribosome entry site (ires) element of fmdv and investigated the effect of ires-specific mirnas on fmdv replication in baby hamster kidney (bhk-21) cells and su ...201424393133
resiquimod and polyinosinic-polycytidylic acid formulation with aluminum hydroxide as an adjuvant for foot-and-mouth disease vaccine.toll-like receptor (tlr) agonists reportedly have potent antiviral and antitumor activities and may be a new kind of adjuvant for enhancing immune efficacy. resiquimod (r848) is an imidazoquinoline compound with potent antiviral activity and functions through the tlr7/tlr8 myd88-dependent signaling pathway. polyinosinic-polycytidylic acid [poly(i:c)] is a synthetic analog of double-stranded rna that induces the production of pro-inflammatory cytokines by the activation of nf-κb through tlr3. thi ...201424386990
design and synthesis of irreversible inhibitors of foot-and-mouth disease virus 3c protease.foot-and-mouth disease virus (fmdv) causes a highly infectious and economically devastating disease of livestock. the fmdv genome is translated as a single polypeptide precursor that is cleaved into functional proteins predominantly by the highly conserved viral 3c protease, making this enzyme an attractive target for antiviral drugs. a peptide corresponding to an optimal substrate has been modified at the c-terminus, by the addition of a warhead, to produce irreversible inhibitors that react as ...201424374278
adjuvant effect enhancement of porcine interleukin-2 packaged into solid lipid nanoparticles.in this paper, we investigated the enhancement of adjuvant effects of porcine il-2 (pil-2) by packaging it into a solid lipid nanoparticle (sln) delivery system. sln-pil-2 was prepared using hydrogenated castor oil and polylactide-co-glycolide by double emulsion solvent evaporation methods (w/o/w). in animal trials, balb/c mice were immunized with inactivated foot and mouth disease virus (fmdv) antigen combined with the sln-pil-2 adjuvant on days 0 and 14. antibody titer, splenocyte proliferatio ...201424374120
genetic diversity of serotype a foot-and-mouth disease viruses in kenya from 1964 to 2013; implications for control strategies in eastern africa.serotype a is the most genetically and antigenically diverse of the foot-and-mouth disease virus (fmdv) serotypes. records of its occurrence in kenya date back to 1952 and the antigenic diversity of the outbreak viruses in this region is reflected by the current use of two different vaccine strains (k5/1980 and k35/1980) and previous use of two other strains (k18/66 and k179/71). this study aimed at enhancing the understanding of the patterns of genetic variation of serotype a fmdv in kenya. the ...201424368254
a virus that can take the heat.foot-and-mouth disease virus shows remarkable thermal lability, a property that is a particular problem for vaccine preparations. in this issue of structure, rincón and colleagues show that electrostatic repulsion within the capsid is responsible for this lability, and they present rationally designed mutants with increased thermostability.201425438667
experimental infection of cattle and goats with a foot-and-mouth disease virus isolate from the 2010 epidemic in japan.in this study, we carried out experimental infections in cattle and goats using a foot-and-mouth disease virus (fmdv) isolate from the 2010 epidemic in japan to analyze clinical manifestations, virus-shedding patterns and antibody responses in the animals. we found that the fmdv o/jpn/2010 isolate is virulent in cattle and goats, produces clinical signs, is spread efficiently by direct contact within the same species, and is persistently infectious in cattle. quantitative analysis of levels of v ...201424938483
proof of principle: non-invasive sampling for early detection of foot-and-mouth disease virus infection in wild boar using a rope-in-a-bait sampling technique.in this study we describe the use of a rope-in-a-bait sampling method ("pswab": pathogen sampling wild animals with baits) for non-invasive saliva sampling aimed at the detection of foot-and-mouth disease (fmd) viral genome in wild boar. the pswabs are produced in the form of a standardized product by embedding a 10 cm long cotton rope in a cereal-based bait matrix. to assess the general suitability of this novel sampling technique an animal experiment was conducted to detect fmd viral genome in ...201424930983
complete genome sequence of foot-and-mouth disease virus type a circulating in bangladesh.the complete genome sequence of a foot-and-and mouth disease virus (fmdv) type a strain (ban/ga/sa-197/2013), isolated from gazipur in bangladesh, revealed an 84-nucleotide insertion within the 5'-untranslated region (utr), a lengthened poly(c) tract, and amino acid substitutions at the vp1 region compared to the available genome sequence of the vaccine strain (genbank accession no. hm854025).201424926048
[advances in reverse genetics-based vaccines of foot and mouth disease].reverse-genetic engineering of foot and mouth disease virus (fmdv) can improve the productivity, antigen matching, antigen stability, immune response ability, and biological safety of vaccines, so vaccine candidates with anticipated biological characteristics can be promptly achieved. negative influence in taming of virulent strains can also be decreased or avoided. reverse genetics not only make up for deficiencies like limitation of viral nature, low success rate, and time and energy consuming ...201424923178
rapeseed oil and ginseng saponins work synergistically to enhance th1 and th2 immune responses induced by the foot-and-mouth disease vaccine.previous investigations demonstrated that saponins isolated from the root of panax ginseng c. a. meyer (i.e., ginseng root saponin [gs-r]) had adjuvant activity. in the present study, the combined effects of rapeseed oil (ro) and gs-r on the immune responses elicited by foot-and-mouth disease (fmd) vaccine were investigated by measuring fmd virus (fmdv)-specific antibody levels, cytokine levels, lymphocyte proliferation, and long-lived igg-secreting plasma cells from bone marrow in a mouse model ...201424920601
intratypic heterologous vaccination of calves can induce an antibody response in presence of maternal antibodies against foot-and-mouth disease virus.maternal antibodies can interfere with foot-and-mouth disease vaccination. in this study we determined whether intratypic heterologous vaccination could help to improve herd immunity.201424906852
the silent point mutations at the cleavage site of 2a/2b have no effect on the self-cleavage activity of 2a of foot-and-mouth disease virus.the 2a region of the foot-and-mouth disease virus (fmdv) polyprotein is 18 amino acids in length, and 2a self-cleavage site (2a/2b) contains a conserved amino acid motif g2a/p2b. to investigate the synonymous codon usage for glycine at the 2a/2b cleavage site of fmdv, 66 2a/2b1 nucleotide sequences were aligned and found that the synonymous codon usage of g2a is conserved and ggg was the most frequently used. to examine the role of synonymous codons for g2a in self-cleavage efficiency of 2a/2b, ...201425152485
infection with foot-and-mouth disease virus (fmdv) induces a natural killer (nk) cell response in cattle that is lacking following vaccination.natural killer (nk) cells play a role in innate antiviral immunity by directly lysing virus-infected cells and producing antiviral cytokines such as interferon gamma (ifn-γ). we developed a system for characterizing the bovine nk response to foot-and-mouth disease virus (fmdv), which causes a disease of cloven-hoofed animals and remains a threat to livestock industries throughout the world. il-2 stimulation of pbmc resulted in poor killing of human k562 cells, which are often used as nk target c ...201425150134
forensic interpretation of molecular variation on networks of disease transmission and genetic inheritance.this paper describes the inference-on-networks (ion) framework for forensic interpretat ion of molecular typing data in cases involving allegations of infectious microbial transmission, association of disease outbreaks with alleged sources, and identifying familial relationships using mitochondrial or y chromosomal dna. the framework is applicable to molecular typing data obtained using any technique, including those based on electrophoretic separations. a key insight is that the networks associ ...201425137141
foot-and-mouth disease in asiatic black bears (ursus thibetanus).foot-and-mouth disease (fmd) is a highly contagious, debilitating, and globally significant viral disease typically affecting cloven-hoofed hosts. the diagnosis of fmd in bears in vietnam is described. the current study describes a confirmed case of fmd in a bear species, and the clinical signs compatible with fmd in a malayan sun bear. thirteen asiatic black bears (ursus thibetanus) and 1 malayan sun bear (helarctos malayanus) were apparently affected. in august 2011, an adult bear became letha ...201425135011
investigation of foot-and-mouth disease outbreaks in the mbala and kazungula districts of zambia.foot-and-mouth disease (fmd) is an acute, highly contagious viral infection of domestic and wild cloven-hoofed animals. it is known to be endemic in zambia, with periodic outbreaks occurring in different geographical areas of the country. this study was conducted to investigate the presence of fmd virus (fmdv) in reported fmd-suspected cases in cattle from the kazungula and mbala districts of zambia. sixty epithelial tissues or oesophageal-pharyngeal (op) scrapings (probang samples) were collect ...201425134173
a recombinant porcine circovirus type 2 expressing the vp1 epitope of the type o foot-and-mouth disease virus is infectious and induce both pcv2 and vp1 epitope antibodies.porcine circovirus type 2 (pcv2) is the etiological agent of postweaning multisystemic wasting syndrome, a disease that causes huge economic damage in swine industry. a recombinant pcv2 expressing the neutralizing vp1 epitope (aa 141-160) of the foot-and-mouth disease virus (fmdv) was rescued using an infectious cloning technique. the pcv2 antigen and fmdv-vp1 antigenic epitope of the cloned strain recpcv2-cl-vp1 were confirmed by an immunoperoxidase monolayer assay (ipma) and a capture enzyme-l ...201425117547
sequences outside that of residues 93-102 of 3a protein can contribute to the ability of foot-and-mouth disease virus (fmdv) to replicate in bovine-derived cells.foot-and-mouth disease (fmd) is a highly contagious and economically devastating disease of cloven-hoofed animals. during 2010 and 2011, there was an epidemic of the mya-98 lineage of the southeast asia (sea) topotype in east asia, including china. changes in the fmdv 3a protein have been previously reported to be associated with the inability of fmdv to grow in bovine cells and cause disease in cattle. in this paper, we report the generation of a full-length infectious cdna clone of fmdv o/sea/ ...201425116389
inhibition of the foot-and-mouth disease virus subgenomic replicon by rna aptamers.we have previously documented the inhibitory activity of rna aptamers to the rna-dependent rna polymerase of foot-and-mouth disease virus (3d(pol)). here we report their modification and use with a subgenomic replicon incorporating gfp (pgfp-pac replicon), allowing replication to be monitored and quantified in real-time. gfp expression in transfected bhk-21 cells reached a maximum at approximately 8 h post-transfection, at which time change in morphology of the cells was consistent with a virus- ...201425096816
no significant differences in the breadth of the foot-and-mouth disease serotype a vaccine induced antibody responses in cattle, using different adjuvants, mixed antigens and different routes of administration.inactivated whole virus foot-and-mouth disease (fmd) vaccines are used worldwide for protection against fmd, but not all vaccines induce protection against all genetic variants of the same fmd virus serotype. the aim of this study is to investigate whether the "breadth" of the antibody response against different strains of the same fmd virus serotype in cattle could be improved by using a different adjuvant, a mix of antigens and/or different routes of administration. to this end, six groups of ...201425092634
a critical role of interferon-induced protein ifp35 in the type i interferon response in cells induced by foot-and-mouth disease virus (fmdv) protein 2c.foot-and-mouth disease virus (fmdv) protein 2c is one of the most highly conserved viral proteins among the serotypes of fmdv. however, its effect on host cell response is not very clear. in our previous report, we showed that fmdv protein 2c interacts with cellular protein n-myc and stat interactor (nmi), inducing moderate apoptosis in cells. here, we show that transfection of hek293t cells with pegfp-n1-2c or pegfp-n1-nmi induces activation of type i interferon promoters, leading to delayed ve ...201425085622
characterization of monoclonal antibodies against foot-and-mouth disease virus serotype o and application in identification of antigenic variation in relation to vaccine strain selection.foot-and-mouth disease (fmd) has severe implications for animal farming which leads to considerable financial losses because of its rapid spread, high morbidity and loss of productivity. for these reasons, the use of vaccine is often favoured to prevent and control fmd. selection of the proper vaccine is extremely difficult because of the antigenic variation within fmdv serotypes. the aim of the current study was to produce a panel of mabs and use it for the characterization of new isolates of f ...201425085313
outbreaks and diagnosis of foot-and-mouth disease serotype o in the republic of korea, april-june 2010.thirteen outbreaks of foot-and-mouth disease (fmd) were reported in pigs and cattle in korea between 8 april and 4 june 2010. the fmd virus (fmdv) isolates were of serotype o, indicating that they were related to the virus strains of the southeast asia topotype that are circulating in east asian countries. animals carrying the viruses were identified by reverse transcriptase-polymerase chain reaction (rt-pcr) during a 29-day period between 8 april and 6 may, 2010. prior to this outbreak, these f ...201423164336
epidemiological analysis, serological prevalence and genotypic analysis of foot-and-mouth disease in nigeria 2008-2009.the epidemiological situation of foot-and-mouth disease virus (fmdv) is uncertain in nigeria, where the disease is endemic, and the majority of outbreaks are unreported. control measures for fmd in nigeria are not being implemented due to the absence of locally produced vaccines and an official ban on vaccine importation. this study summarizes the findings of a 3-year study aimed at quantifying the seroprevalence of fmd, its distribution in susceptible species and the genetic diversity of fmdv i ...201423347819
serological evidence indicates that foot-and-mouth disease virus serotype o, c and sat1 are most dominant in eritrea.foot-and-mouth disease (fmd) is endemic in eritrea and in most parts of africa. to be able to control fmd using vaccination, information on the occurrence of various foot-and-mouth disease serotypes in eritrea is needed. in this cross-sectional study, 212 sera samples were collected from fmd infected and recovered animals in eritrea. these samples were tested for the presence of antibodies against fmd non-structural proteins (nsp) and neutralizing antibodies against six of the seven (all but sat ...201423480728
proof of concept for the inhibition of foot-and-mouth disease virus replication by the anti-viral drug 2'-c-methylcytidine in severe combined immunodeficient mice.recent european contingency plans envisage emergency vaccination as an animal-friendly control strategy for foot-and-mouth disease (fmd). anti-viral drugs may be used as an alternative or complementary measure. we here demonstrate that the nucleoside analogue 2'-c-methylcytidine (2'cmc) protects severe combined immunodeficient (scid) mice against lethal fmd virus infection. in brief, scid mice were inoculated with serotype a fmd virus and treated for five consecutive days with 2'cmc. all 15 trea ...201423480064
genetic basis of antigenic variation in foot-and-mouth disease serotype a viruses from the middle east.foot-and-mouth disease viruses (fmdv) from serotype a exhibit high antigenic diversity. within the middle east, a strain called a-iran-05 emerged in 2003, and subsequently replaced the a-iran-96 and a-iran-99 strains that were previously circulating in the region. viruses from this strain did not serologically match with the established a/iran/96 vaccine, although most early samples matched with the older a22/iraq vaccine. however, many viruses from this strain collected after 2006 had poor sero ...201424035435
foot and mouth disease virus-loaded fungal chitosan nanoparticles for intranasal administration: impact of formulation on physicochemical and immunological characteristics.nasal vaccination is a promising, needle-free alternative route for parenteral vaccination. this study introduces a simple, scalable nasal vaccine delivery formulation for foot and mouth disease virus (fmdv) using chitosan (cs) nanoparticles and assesses the potential of fungal cs for use as nanocarriers for mucosal vaccines. fungal cs was extracted from fungal biomass and physiochemically characterized. fmdv-loaded cs nanoparticles, prepared using an ionic gelation technique, were characterized ...201423590209
co-inoculation of baculovirus and fmdv vaccine in mice, elicits very early protection against foot and mouth disease virus without interfering with long lasting immunity.baculoviruses (bvs) potentiate the immune response against soluble antigens. we investigated whether bv could be used as immunoactivator in foot-and-mouth disease (fmd) vaccines using the balb/c mouse model. mice were vaccinated with a single dose of inactivated fmdv (ifmdv), ifmdv+bv, bv, or culture medium. humoral and cellular immune responses were higher in animals immunized with ifmdv+bv than in mice vaccinated with ifmdv alone. animals receiving ifmdv+bv had significantly lower viremia at 2 ...201323588086
development and evaluation of multiplex rt-lamp assays for rapid and sensitive detection of foot-and-mouth disease virus.this paper describes the evaluation of four novel real-time multiplex reverse transcription loop-mediated isothermal amplification (rt-lamp) assays for rapid and sensitive diagnosis of foot-and-mouth disease (fmd). in order to overcome the genetic diversity of fmd viruses (fmdv), these multiplex rt-lamp assay pairs were established by combining four newly designed primer sets with two primer sets that had been previously published. using a real-time turbidimeter to detect amplification products ...201323583488
repeated exposure to 5d9, an inhibitor of 3d polymerase, effectively limits the replication of foot-and-mouth disease virus in host cells.foot-and-mouth disease (fmd) is a highly contagious disease of livestock caused by a highly variable rna virus (fmdv) that has seven serotypes and more than sixty subtypes. both prophylactic and post-infection means of controlling the disease outbreak, including universally applicable vaccines and emergency response measures such as therapeutic treatments, are on high demand. in this study, we analyzed the long-term exposure outcome to a previously identified inhibitor of 3d polymerase (fmdv 3dp ...201323578728
regulation of porcine plasmacytoid dendritic cells by cytokines.plasmacytoid dendritic cells (pdc) are the most potent producers of type-i interferon (ifn) and represent the main interferon (ifn)-α source in response to many viruses. considering the important roles played by type i ifn's, not only as antiviral effectors but also as potent alarming cytokine of the immune system, we investigated how such responses are regulated by various cytokines. to this end, we stimulated enriched pdc in the presence or absence of particular cytokines with a strong activat ...201323577175
vp1 protein of foot-and-mouth disease virus (fmdv) impairs baculovirus surface display.the foot-and-mouth disease virus (fmdv) causes important economical losses in livestock farming. in order to develop a novel subunit vaccine against fmdv, we constructed recombinant baculoviruses that display the protein vp1 of fmdv on their surface, with either polar (fused to gp64) or nonpolar (fused to anchor membrane from vsv-g protein) distribution. insect cells infected with the different recombinant baculoviruses expressed vp1 fusion protein to high levels. however, the recombinant vp1 pr ...201323566950
an infectious recombinant foot-and-mouth disease virus expressing a fluorescent marker protein.foot-and-mouth disease virus (fmdv) is one of the most extensively studied animal pathogens because it remains a major threat to livestock economies worldwide. however, the dynamics of fmdv infection are still poorly understood. the application of reverse genetics provides the opportunity to generate molecular tools to further dissect the fmdv life cycle. here, we have used reverse genetics to determine the capsid packaging limitations for a selected insertion site in the fmdv genome. we show th ...201323559477
association of bola drb3 alleles with variability in immune response among the crossbred cattle vaccinated for foot-and-mouth disease (fmd).polymorphism of bovine leukocyte antigen (bola) drb3 gene is being intensively investigated for potential association with economically important diseases of cattle. accordingly, we investigated the association of drb3 exon 2 polymorphism as evidenced by the variation in the binding pockets with variability in immune response to inactivated trivalent (o, a and asia1) foot and mouth disease virus (fmdv) vaccine in a closed population of crossbred cattle. antibody titer of ≥ 1.8 was set as the cut ...201323541924
expanding the spectral palette of fluorescent proteins for the green microalga chlamydomonas reinhardtii.fluorescent proteins (fps) have become essential tools for a growing number of fields in biology. however, such tools have not been widely adopted for use in microalgal research. the aim of this study was to express and compare six fps (blue mtagbfp, cyan mcerulean, green crgfp, yellow venus, orange tdtomato and red mcherry) in the popular model microalga chlamydomonas reinhardtii. to circumvent the transgene silencing that often occurs in c. reinhardtii, the fps were expressed from the nuclear ...201323521393
a continuous bovine kidney cell line constitutively expressing bovine αvβ6 integrin has increased susceptibility to foot-and-mouth disease virus.foot-and-mouth disease (fmd) is a worldwide problem limiting the trade of animals and their products from affected countries. the rapid isolation, serotyping, and vaccine matching of fmd virus from disease outbreaks is critical for enabling the implementation of effective vaccination programs and to stop the spread of infection during outbreaks. some primary cells have been shown to be highly susceptible to most strains of fmd virus (fmdv) but are difficult and expensive to prepare and maintain. ...201323515553
influence of the leader protein coding region of foot-and-mouth disease virus on virus replication.the foot-and-mouth disease virus (fmdv) leader (l) protein is produced in two forms, lab and lb, differing only at their amino-termini, due to the use of separate initiation codons, usually 84 nt apart. it has been shown previously, and confirmed here, that precise deletion of the lab coding sequence is lethal for the virus, whereas loss of the lb coding sequence results in a virus that is viable in bhk cells. in addition, it is now shown that deletion of the 'spacer' region between these two in ...201323515027
evolutionary conserved motifs constrain the rna structure organization of picornavirus ires.picornavirus rnas initiate translation using a 5' end-independent mechanism based on internal ribosome entry site (ires) elements. despite performing similar functions, ires elements present in genetically distant rnas differ in primary sequence, rna secondary structure and trans-acting factors requirement. the lack of conserved features amongst iress represents obstacles for the understanding of the internal initiation process. rna structure is tightly linked to picornavirus ires activity, cons ...201323507141
the effects of the synonymous codon usage and trna abundance on protein folding of the 3c protease of foot-and-mouth disease virus.the 3c protease of foot-and-mouth disease virus (fmdv) has a conserved amino acid sequence and is responsible for most cleavage in the viral polyprotein. the effects of the synonymous codon usage of fmdv 3c gene and trna abundance of the hosts on shaping different folding units (α-helix, β-strand and the coil) in the 3c protease were analyzed based on the structural information of the fmdv 3c protease from protein data bank (pdb: 2bhg) and 210 genes of 3c for all serotypes of fmdv. the strong co ...201323499709
foot-and-mouth disease virus carrier status in bos grunniens yaks.the carrier status of foot-and-mouth disease virus (fmdv) is complicated, and the role of carrier animals in virus transmission is controversial. to investigate the carrier status of fmdv in animals that live in high altitude, bos grunniens yaks were infected experimentally with fmdv o/akesu/58.201323497369
bovine fetal epithelium cells expressing shrna targeting viral vp1 gene resisted against foot-and-mouth disease virus.rnai could protect experimental animals from foot-and-mouth disease virus (fmdv), but pivotal issue is delivery of rnai. in this study, shrna recombinant lentiviral plasmid rnai-lt6 targeting vp1 of fmdv, which strongly suppressed the transient expression of a flag-tagged vp1 protein in 293t cells and significantly inhibited viral replication in bhk-21 cells, was screened and transfected into bovine fetal fibroblast cells. with subsequent somatic cell cloning, three 4-month-old transgenic fetuse ...201323481248
[evaluation of synthetic peptide vaccines against foot-and-mouth disease type a].we developed a synthetic vaccine against foot-and-mouth disease type a.201324028062
targeted delivery of vp1 antigen of foot-and-mouth disease virus to m cells enhances the antigen-specific systemic and mucosal immune response.application of vaccine materials through oral mucosal route confers great economical advantage in animal farming industry due to much less vaccination cost compared with that of injection-based vaccination. in particular, oral administration of recombinant protein antigen against foot-and-mouth disease virus (fmdv) is an ideal strategy because it is safe from fmdv transmission during vaccine production and can induce antigen-specific immune response in mucosal compartments, where fmdv infection ...201324009543
multiple introductions of serotype o foot-and-mouth disease viruses into east asia in 2010-2011.foot-and-mouth disease virus (fmdv) is a highly contagious and genetically variable virus. sporadic introductions of this virus into fmd-free countries may cause outbreaks with devastating consequences. in 2010 and 2011, incursions of the fmdv o/sea/mya-98 strain, normally restricted to countries in mainland southeast asia, caused extensive outbreaks across east asia. in this study, 12 full genome fmdv sequences for representative samples collected from the people's republic of china (pr china) ...201324007643
foot-and-mouth disease virus 3c protease induces fragmentation of the golgi compartment and blocks intra-golgi transport.picornavirus infection can cause golgi fragmentation and impose a block in the secretory pathway which reduces expression of major histocompatibility antigens at the plasma membrane and slows secretion of proinflammatory cytokines. in this study, we show that golgi fragmentation and a block in secretion are induced by expression of foot-and-mouth disease virus (fmdv) 3c(pro) and that this requires the protease activity of 3c(pro). 3c(pro) caused fragmentation of early, medial, and late golgi com ...201323986596
antigenic heterogeneity of capsid protein vp1 in foot-and-mouth disease virus (fmdv) serotype asia 1.foot and mouth disease virus (fmdv), with its seven serotypes, is a highly contagious virus infecting mainly cloven-hoofed animals. the serotype asia1 occurs mainly in asian regions. an in-silico approach was taken to reveal the antigenic heterogeneities within the capsid protein vp1 of asia1. a total of 47 vp1 sequences of asia1 isolates from different countries of south asian regions were selected, retrieved from database, and were aligned. the structure of vp1 protein was modeled using a homo ...201323983476
transient gene expression in serum-free suspension-growing mammalian cells for the production of foot-and-mouth disease virus empty capsids.foot-and-mouth disease (fmd) is a highly contagious disease of cloven-hoofed animals. it produces severe economic losses in the livestock industry. currently available vaccines are based on inactivated fmd virus (fmdv). the use of empty capsids as a subunit vaccine has been reported to be a promising candidate because it avoids the use of virus in the vaccine production and conserves the conformational epitopes of the virus. in this report, we explored transient gene expression (tge) in serum-fr ...201323977353
novel immunogenic baculovirus expressed virus-like particles of foot-and-mouth disease (fmd) virus protect guinea pigs against challenge.vaccination is a well accepted strategy for control of foot-and-mouth disease (fmd) in endemic countries. currently, chemically inactivated virus antigens are used for preparation of fmd vaccine. to develop a non-infectious and safe recombinant vaccine, we expressed structural polypeptide of fmdv (o/ind/r2/75) using baculovirus expression system. we show that inclusion of mutated viral 3c protease in frame with the polypeptide (p1-2a), enhanced the yield of structural proteins. the structural pr ...201323969204
optimisation of the foot-and-mouth disease virus 2a co-expression system for biomedical applications.many biomedical applications require the expression or production of therapeutic hetero-multimeric proteins/protein complexes: in most cases only accomplished by co-ordinated co-expression within the same cell. foot-and-mouth disease virus 2a (f2a) and '2a-like' sequences are now widely used for this purpose. since 2a mediates a co-translational 'cleavage' at its own c-terminus, sequences encoding multiple proteins (linked via 2as) can be concatenated into a single orf: a single transgene. it ha ...201323968294
processing of the vp1/2a junction is not necessary for production of foot-and-mouth disease virus empty capsids and infectious viruses: characterization of "self-tagged" particles.the foot-and-mouth disease virus (fmdv) capsid protein precursor, p1-2a, is cleaved by 3c(pro) to generate vp0, vp3, vp1, and the peptide 2a. the capsid proteins self-assemble into empty capsid particles or viruses which do not contain 2a. in a cell culture-adapted strain of fmdv (o1 manisa [lindholm]), three different amino acid substitutions (e83k, s134c, and k210e) were identified within the vp1 region of the p1-2a precursor compared to the field strain (wild type [wt]). expression of the o1 ...201323966400
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