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the picornavirus replication inhibitors hbb and guanidine in the echovirus-9 system: the significance of viral protein 2c.hbb [2-(alpha-hydroxybenzyl)-benzimidazole] and guanidine are potent inhibitors of picornavirus replication. among other evidence, limited cross-resistance and a synergistic effect of both inhibitors suggest similar but not identical mechanisms of antiviral action. echovirus-9 variants resistant to each of these drugs were characterized and sequenced. complete resistance to hbb or guanidine was shown to be due to single but different point mutations in the non-structural protein 2c. protein 2c w ...200010725414
molecular analysis of the prototype coxsackievirus b5 genome.to facilitate studies of the phylogenetic relationship between enteroviruses, in particular the prototype strain (faulkner) of coxsackievirus b5 (cvb5f) and other cvb5 isolates and to facilitate studies of the interactions between cvb5f and the target cell, the complete nucleotide sequence of the prototype has been determined. the complete sequence was collected from three overlapping reverse transcription polymerase chain reaction (rt-pcr) generated amplicons. molecular analysis of the cvb5f ge ...200010752549
a group b coxsackievirus/poliovirus 5' nontranslated region chimera can act as an attenuated vaccine strain in mice.the linear, single-stranded enterovirus rna genome is flanked at either end with a nontranslated region (ntr). by replacing the entire 5' ntr of coxsackievirus b3 (cvb3) with that from type 1 poliovirus, a progeny virus was obtained following transfection of hela cells. the chimeric virus, cpv/49, replicates like the parental cvb3 strain in hela cells but is attenuated for replication and yield in primary human coronary artery endothelial cell cultures, in a human pancreas tumor cell line, and i ...200010756016
role of mip-2 in coxsackievirus b3 myocarditis.interleukin-8 (il-8) is a chemotactic cytokine for neutrophils and lymphocytes. macrophage inflammatory protein-2 (mip-2) is a murine counterpart of il-8. the present study was performed to determine the role of mip-2 in murine myocarditis. we examined (1) the mip-2 producing activity of coxsackievirus b3 (cb3)-infected cultured macrophages, (2) serial plasma mip-2 levels in cb3-induced mice by enzyme-linked immunosorbent assay (elisa), and (3) the effects of anti-mouse mip-2 monoclonal antibody ...200010756119
echovirus infection of rhabdomyosarcoma cells is inhibited by antiserum to the complement control protein cd59.a number of echoviruses use decay accelerating factor (daf) as a cellular receptor or attachment protein for cell infection. binding of echovirus 7 to daf at the cell surface, but not to soluble daf in solution, triggers the formation of virus particles exhibiting an altered sedimentation coefficient ('a' particles) which are considered indicative of the particle uncoating process. we have previously demonstrated that antibodies to beta(2)-microglobulin block cell infection at a stage prior to ' ...200010769083
immune recognition of swine vesicular disease virus structural proteins: novel antigenic regions that are not exposed in the capsid.swine vesicular disease virus (svdv) is an enterovirus of the picornaviridae family that belongs to the coxsackievirus b group. a number of antigenic sites have been identified in svdv by analysis of neutralizing monoclonal antibody-resistant mutants and shown to be exposed on the surface of the capsid. in this paper we have identified seven new immunodominant antigenic regions in svdv capsid proteins by a peptide scanning method, using a panel of sera from infected pigs. when these antigenic re ...200010772981
expression of an antigenic adenovirus epitope in a group b coxsackievirus.group b coxsackieviruses (cvb) cause human myocarditis, while human adenovirus type 2 (ad2) is implicated as an agent of this disease. the l1 loop of the ad2 hexon protein has been demonstrated to be antigenic in rabbits. to evaluate the feasibility of a multivalent vaccine strain against the cvb and ad2, we cloned the sequence encoding the ad2 hexon l1 loop, flanked by dissimilar sequences encoding the protease 2a (2apro) recognition sites, into the genome of an attenuated strain of cvb type 3 ...200010775593
genomic determinants of cardiovirulence in coxsackievirus b3 clinical isolates: localization to the 5' nontranslated region.coxsackievirus b3 (cvb3) infections can cause myocarditis in humans and are implicated in the pathogenesis of dilated cardiomyopathy. the natural genetic determinants of cardiovirulence for cvb3 have not been identified, although using strains engineered in the laboratory, cardiovirulence determinants have been identified in the cvb3 5' nontranslated region (5'ntr) and capsid. the myocarditic phenotypes of two cvb3 clinical isolates were determined using an established murine model of inflammato ...200010775617
the coxsackie-adenovirus receptor (car) is used by reference strains and clinical isolates representing all six serotypes of coxsackievirus group b and by swine vesicular disease virus.group b coxsackieviruses are etiologically linked to many human diseases, and cell surface receptors are postulated to play an important role in mediating their pathogenesis. the coxsackievirus adenovirus receptor (car) has been shown to function as a receptor for selected strains of coxsackievirus group b (cvb) serotypes 3, 4, and 5 and is postulated to serve as a receptor for all six serotypes. in this study, we demonstrate that car can serve as a receptor for laboratory reference strains and ...200010814575
reverse transcription of an rna genome from databasing paper (fta(r)).the instability of rna in solutions during storage and travel is an impediment to its utilization in routine diagnostics. a robust and simple approach to the problem of rna protection and processing is offered by storage of rna desiccated with processing procedures that do not solublize the rna until the beginning of reverse transcription. the feasibility of this general approach was tested with coxsackievirus b4 (cvb-4) from blood or culture fluid held on a storage and transport medium (fta(r)) ...200010814592
[therapy and prognosis of infectious complete atrioventricular block in children].from 1983 to 1997, we have studied ten children with complete atrioventricular block likely due to myocarditis in order to assess its prognosis and to define a therapeutic strategy. their age ranged from 6 days to 16 years (median: 4.1 years). all were admitted for sudden complete block, with symptoms in seven: syncope or fainting, seizures, collapse. three had an asymptomatic bradycardia which was detected on routine auscultation in children with fever or already hospitalized; fever was present ...200010858852
coxsackievirus infection of the pancreas: evaluation of receptor expression, pathogenesis, and immunopathology.coxsackievirus type b (cvb) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, t cells, and macrophages and leads to the destruction of exocrine tissue. the physiological manifestations of pancreatic cvb infection are correlated with viral tropism; the virus infects acinar cells but spares the islets of langerhans. here we evaluate the mechanisms underlying pancreatic inflammation and destruction and identify the determinants of viral tropism. t-cel ...200010860882
aloe polymannose enhances anti-coxsackievirus antibody titres in mice.aloe polymannose (ap), a high mannose biological response modifier (brm) purified from the aloe barbadensis miller plant, was tested for activity in enhancing antibody titres against coxsackievirus b3 (cvb3) and cvb3-induced myocarditis in murine models of the disease. inoculation of mice with ap over a range of three nontoxic doses and in varying schedules did not reduce virus titres in heart tissues or ameliorate virus-induced cardiopathological alterations during acute disease. however, this ...200010861969
coxsackie b virus-induced autoimmunity to gad does not lead to type 1 diabetes. 200010895859
molecular pathology and structural features of enteroviral replication. toward understanding the pathogenesis of viral heart disease.enteroviruses of the picornaviridae and primarily coxsackieviruses of group b (cvb) can be detected in humans and various experimental murine models of acute myocarditis and chronic heart muscle diseases indicating enterovirus persistence in the myocardium. persistent myocardial infection is characterized by restricted viral replication and gene expression in myocytes capable of sustaining chronic inflammation. viral cytotoxicity was found to be crucial for organ pathology both during acute and ...200010904841
enteroviral and immune mediated myocarditis in scid mice.severe combined immune deficiency (scid) mice have been used as an animal model to study both the direct cytopathic effect of enteroviruses on the heart in the absence of an effective immune system and to investigate the role of immune mediated processes in the pathogenesis of human myocarditis. the infection of scid mice with coxsackievirus b3 resulted in severe myocarditis with very high titers of the virus in the myocardium and severe necrosis of myocytes. this direct cytopathic effect caused ...200010904845
the outcome of coxsackievirus b3-(cvb3-) induced myocarditis is influenced by the cellular immune status.mice develop a marked age-related susceptibility to myocardial coxsackievirus b3 (cvb3) infections. the lesions observed in mice resemble closely those seen in the human disease. experimental murine models of cvb3-induced myocarditis have shown that both, host and viral genetic factors, can influence susceptibility to the infection as well as the persistence and progression of the disease. recently, we have shown that cd4 t cell-deficient mhc class ii knockout mice develop a strong fibrosis with ...200010904846
expression of inducible nitric oxide synthase in experimental viral myocarditis.nitric oxide (no) is an important bioactive molecule with regulatory, cytotoxic or cytoprotective properties. in virus-induced myocarditis, no mediates host defense mechanisms against the infection or causes cardiac dysfunctions. no is synthesized from l-arginine by the enzyme nitric oxide synthase (nos). the expression of the inducible form of the nitric oxide synthase (inos) is regulated by cytokines, involved in the complex myocardial immune response to enterovirus infections. the present stu ...200010904848
initial interactions of subgenus d adenoviruses with a549 cellular receptors: sialic acid versus alpha(v) integrins.selected members of the adenovirus family have been shown to interact with the coxsackie adenovirus receptor, alpha(v) integrins, and sialic acid on target cells. initial interactions of subgenus d adenoviruses with target cells have until now been poorly characterized. here, we demonstrate that adenovirus type 8 (ad8), ad19a, and ad37 use sialic acid as a functional cellular receptor, whereas the ad9 and ad19 prototypes do not.200010906228
redistribution of accumulated 2,3,7,8-tetrachlorodibenzo-p-dioxin during coxsackievirus b3 infection in the mouse.the tissue redistribution of accumulated 2,3,7, 8-tetrachlorodibenzo-p-dioxin (tcdd) during infection was studied in adult male a/j mice using a common human virus coxsackievirus b3. before infection (day 1), all mice were injected intraperitoneally (i.p.) with 1 microci 3h-tcdd, corresponding to 0.5 microg tcdd kg(-1). one group was sacrificed before virus inoculation (day 0). of the remaining mice, one subgroup was inoculated i.p. with cb3 virus while the other subgroup served as a noninfected ...200010906430
nosocomial transmission of echovirus 30: molecular evidence by phylogenetic analysis of the vp1 encoding sequence.we investigated six cases of enterovirus infection in a neonatal unit. the index patient, a 5-day-old boy, was admitted with aseptic meningitis due to echovirus 30 (e30). secondary infections with e30 occurred in five babies. comparison of the complete vp1 sequences showed that the isolates recovered from the index patient and his mother were closely related to those recovered from the five babies with secondary infections, demonstrating a nosocomial transmission of the virus. in the phylogeneti ...200010921945
t-cell responses to enterovirus antigens in children with type 1 diabetes.enterovirus infections, implicated in the pathogenesis of type 1 diabetes in a number of studies, may precipitate the symptoms of clinical diabetes and play a role in the initiation of the beta-cell damaging process. the aim of this study was to evaluate whether cellular immune responses to enterovirus antigens are abnormal in children with type 1 diabetes. lymphocyte proliferation responses to enterovirus antigens were analyzed in 41 children with new-onset type 1 diabetes, 23 children with typ ...200010923630
coxsackievirus expression of the murine secretory protein interleukin-4 induces increased synthesis of immunoglobulin g1 in mice.we cloned the sequence encoding murine interleukin-4 (mil-4), including the secretory signal, into the genome of cvb3/0, an artificially attenuated strain of coxsackievirus b3, at the junction of the capsid protein 1d and the viral protease 2apro. two strains of chimeric cvb3 were constructed using, in one case, identical sequences to encode 2apro cleavage sites (cvb3/0-mil4/47) on either side of the inserted coding sequence and, in the other case, nonidentical sequences that varied at the nucle ...200010933703
group b coxsackievirus myocarditis and pancreatitis: connection between viral virulence phenotypes in mice.the group b coxsackieviruses (cvb) induce experimental pancreatitis and myocarditis in mice and are established agents of human myocarditis, especially in children. we tested the hypothesis that the development of cvb-induced myocarditis is linked to cvb-induced pancreatitis by studying the replication of different cvb strains in mice. eight of nine genotypically different type 3 cvb (cvb3) strains induced acute pancreatitis in mice; of these, three viruses also induced acute myocarditis. one cv ...200010935991
t-cell reactivity to the p2c nonstructural protein of a diabetogenic strain of coxsackievirus b4.enteroviruses are proposed as initiating factors in the etiology of type 1 diabetes mellitus (type 1 dm). molecular mimicry between the autoantigen glutamic acid decarboxylase 65 (gad65) and the coxsackievirus b4 (cvb4) nonstructural protein p2c is frequently cited as a mechanism by which this virus triggers the disease, but little is known about the immunogenicity of this viral protein in humans, mainly due to the problem of obtaining highly pure preparations of p2c. we generated large amounts ...200010936088
singleton reactors in the diagnosis of swine vesicular disease: the role of coxsackievirus b5.swine vesicular disease virus (svdv) and coxsackie b5 virus (cvb5) are closely related viruses that can infect swine and man and give rise to cross-reacting serum antibodies. it is, therefore, possible that svd antibodies found in serologic screenings of pigs are induced by cvb5. single positive animals found in screening programmes are generally referred to as singleton reactors (sr). to determine whether sr in svdv screenings are induced by cvb5 infection, virus neutralisation tests (vnts) and ...200010973703
antiviral effect of the combination of enviroxime and disoxaril on coxsackievirus b1 infection.effects of enviroxime and disoxaril, inhibitors of replication of some picornaviruses with known mechanisms of action, alone or in combination, on replication of coxsackievirus b1 (cvb1) in fl cells and on experimental cvb1 infection in newborn mice were tested. the combination of enviroxime and disoxaril resulted in vitro in a synergistic interaction. both compounds were administered in vivo, alone or in combination, daily by subcutaneous (s.c.) route since the day of virus inoculation till the ...200010989697
early alteration of nucleocytoplasmic traffic induced by some rna viruses.a hela cell line expressing the green fluorescent protein fused to the sv40 t-antigen nuclear localization signal (egfp-nls) was established. fluorescence in these cells was confined to the nuclei. after poliovirus infection, cytoplasmic fluorescence in a proportion of cells could be detected by 1 h postinfection (p.i.) and in virtually all of the fluorescent cells by 2 h p.i. the relocation could be prevented by cycloheximide but not by inhibition of poliovirus replication by guanidine. hcl. nu ...200010998323
attachment of coxsackievirus b3 variants to various cell lines: mapping of phenotypic differences to capsid protein vp1.the coxsackievirus b3 (cvb3) strain nancy p establishes a persistent carrier-state infection without visible cytopathic effect in primary human fibroblasts (hufi h), whereas the derivative variant pd induces a complete lysis of the cell monolayer. to define the molecular basis of this exceptional growth property, the complete genomes of both viruses were sequenced and compared to all published sequences of cvb3. as a result, six unique amino acid substitutions in the vp1 capsid protein were obse ...200011017789
persistent infection of human pancreatic islets by coxsackievirus b is associated with alpha interferon synthesis in beta cells.the interactions of coxsackievirus b3 (cvb3), cvb4e2 (diabetogenic), and cvb4jbv (nondiabetogenic) strains with human pancreatic islets from eight adult brain-dead donors were investigated. persistent replication of viruses in human islets was proved by detection of viral rna by in situ hybridization, vp1 capsid protein by immunofluorescence (if) staining, negative-strand viral rna by reverse transcription-pcr in extracted rna from islets, and release of infectious particles up to 30 days after ...200011024144
v gamma 1+ t cells suppress and v gamma 4+ t cells promote susceptibility to coxsackievirus b3-induced myocarditis in mice.coxsackievirus b3 infections of c57bl/6 mice, which express the mhc class ii ia but not ie ag, results in virus replication in the heart but minimal myocarditis. in contrast, bl.tg.ealpha mice, which are c57bl/6 mice transgenically induced to express ie ag, develop significant myocarditis upon coxsackievirus b3 infection. despite this difference in inflammatory damage, cardiac virus titers are similar between c57bl/6 and bl.tg.ealpha mice. removing gammadelta t cells from either strain by geneti ...200011035049
quantitative analysis of viral rna kinetics in coxsackievirus b3-induced murine myocarditis: biphasic pattern of clearance following acute infection, with persistence of residual viral rna throughout and beyond the inflammatory phase of disease.although the association remains controversial, enteroviruses have been implicated in the aetiology of several chronic diseases of humans. to further understand the mechanism of enterovirus persistence and its relationship to organ pathology, virus infectivity and viral rna kinetics in the heart and other target organs during acute and persistent phases of murine coxsackievirus b3 infection were investigated. these studies revealed a biphasic pattern of virus clearance. thus, there was a rapid b ...200011038389
trace element changes in the myocardium during coxsackievirus b3 myocarditis in the mouse.during most infections plasma, concentrations of trace elements change, but it is unclear if this reflects changes in infected target tissues. in coxsackievirus b3 (cb3) infection, the myocardium is a target in both humans and mice. the concentrations of 12 trace elements were analyzed by inductively coupled plasma-mass spectrometry (icp-ms) in the myocardium of sham-inoculated controls and infected a/j mice 4 and 7 d postinoculation. the size of the inflammatory lesion was positively correlated ...200011049229
acute onset of type i diabetes mellitus after severe echovirus 9 infection: putative pathogenic pathways.enterovirus infections have been implicated in the development of type i diabetes mellitus. they may cause beta cell destruction either by cytolytic infection in the pancreas or indirectly by contributing to autoimmune reactivity. we sought evidence for these 2 mechanisms in a case of acute-onset diabetes mellitus that occurred during severe echovirus 9 infection. the virus was isolated and administered to cultured human beta cells. no viral proliferation was observed, and no beta cell death was ...200011049787
nitric oxide and viral cardiomyopathy. 200011056085
limited proteolysis of the coxsackievirus and adenovirus receptor (car) on hela cells exposed to trypsin.trypsin treatment of hela cells results in a limited proteolysis of the coxsackievirus and adenovirus receptor (car) after which the cleaved car remains cell-associated and tryptic peptides remain associated through disulfide bonds. trypsin-treated hela cells remain susceptible to infection with coxsackievirus b and produce progeny virus at 8 h post-infection in amounts comparable to cells with intact car. hela cells remove the proteolysed car within 15 h and require over 24 h to restore intact ...200011068050
mutations in a conserved enteroviral rna oligonucleotide sequence affect positive strand viral rna synthesis.we showed earlier that a transition mutation u234c, located within the completely conserved 5 nucleotide (nt) tract 5'-cguua (nt232-236) in the 5' non-translated region (ntr) of the coxsackievirus b3 (cvb3) genome, attenuated cvb3 cardiovirulence in mice. to further explore the role of the sequence, we induced two single and one double transversion mutations in the conserved 5mer in a cardiovirulent cvb3 genome. the mutated sites partially or totally reverted to parental wild-type when progeny v ...200011087092
sero-surveillance of wild boar in the netherlands, 1996-1999.from 1996 to 1999, blood samples were collected from wild boar shot during the hunting season in crown properties, national parks and the free wildlife belt in the netherlands. sera were screened for the presence of antibodies against classical swine fever virus (csfv), swine vesicular disease virus (svdv), aujeszky's disease virus (adv) and trichinella spiralis. the results of the sero-surveillance system indicate that csfv, svdv and adv are uncommon within the wild boar population. hence, the ...200011107628
immunogenicity of a foreign peptide expressed within a capsid protein of an attenuated coxsackievirus.the immunogenicity of soluble peptides can be improved by expression within recombinant microorganisms. the immunogenicity of a peptide expressed within a capsid protein of an attenuated coxsackievirus b4 was evaluated. the insertion site was chosen based on its antigenic structure. a foreign peptide was inserted into a region of the vp1 capsid protein that was identified as a t helper cell epitope. a recombinant virus containing ten amino acids of ovalbumin sequence was genetically stable and r ...200011115722
micronutrients and host resistance to viral infection.previous work in our laboratory demonstrated that a virus could undergo rapid mutation in a host deficient in se, leading to a normally avirulent virus acquiring virulence due to genome changes. once these mutations occur, even a host with adequate se-nutriture is susceptible to the newly virulent virus. what influence does the deficiency in se have on the immune response of the host? infection with myocarditic strains of coxsackievirus induces an inflammatory response in the cardiac tissue. it ...200011115793
development and evaluation of quantitative-competitive pcr for quantitation of coxsackievirus b3 rna in experimentally infected murine tissues.a method is described for quantitation of enterovirus rna in experimentally infected murine tissues. viral rna was extracted from tissue samples and amplified by reverse transcriptase pcr in the presence of an internal standard rna. the ratio of pcr product derived from viral rna and internal standard rna was then determined using specific probes in a post-pcr electrochemiluminescent hybridization assay. this provided an estimate of the viral rna copy number in the original sample, and detection ...199910894631
persistent fever as the only manifestation of chronic coxsackievirus b4 infection in the brain of a human immunodeficiency virus type 1-infected child. 199910825062
'in vitro' antiviral activity of neem (azadirachta indica. a. juss) leaf extract against group b coxsackieviruses.the antiviral and virucidal effect of methanolic extract fraction of leaves of neem (azadirachta indica a. juss) (ncl-11) was studied regarding its activity and possible mechanism of action against coxsackie b group of viruses. ncl-11 inhibited plaque formation in 6 antigenic types of coxsackie virus b at a concentration of 1000 micrograms/ml at 96 hrs. 'in vitro'. additionally virus inactivation, yield reduction and effect of time of addition assays suggested that ncl-11 was most effective agai ...199910810594
coxsackievirus b3-induced chronic myocarditis in outbred nmri mice.the pathogenesis of coxsackievirus b3 (cvb3)-induced myocarditis was investigated in adult han:nmri mice. the outbred model, in comparison with inbred models, represents better the natural variable susceptibility of the human population.199910774554
selenium and viral virulence.a mouse model of coxsackievirus-induced myocarditis is being used to investigate nutritional determinants of viral virulence. this approach was suggested by research carried out in china which showed that mice fed diets composed of low selenium ingredients from a keshan disease area suffered more extensive heart damage when infected with a coxsackie b4 virus than infected mice fed the same diet but supplemented with selenium by esophageal intubation. selenium deficiency in our mice increased the ...199910746343
secondary heterotypic versus homotypic infection by coxsackie b group viruses: impact on early and late histopathological lesions and virus genome prominence.the impact of prior exposure to a different or identical strain of coxsackievirus b (cvb) on murine cvb myocarditis was studied using a susceptible murine host (a/j[h-2a]) and myocarditic cvb3 or avirulent cvb2 as primary or secondary infectants. the effects of secondary heterotypic infection (cvb2 followed by cvb3) and homotypic infection (cvb3 followed by cvb3) 28 days after primary inoculation, versus cvb2 or cvb3 alone, on injury and viral genomic replication, both early (day 7) and late (da ...199910724506
the investigations into the interferon-like activity of polygonum l. genus.the interferon inducing abilities of eleven ethanolic extracts obtained from nine taxons of polygonum l. genus, were tested in the cell culture of monkey kidney. the extracts from the herb of polygonum amphibium l. and the rhizome and fruit of polygonum bistorta l. induced a substance showing an interferon-like activity. biological activity studies showed that the protective titre (the highest dilution which protected cells by 50% against virus infection) of the interferon-like materials was 1:1 ...199910715890
disturbance of myocardial energy metabolism in experimental virus myocarditis by antibodies against the adenine nucleotide translocator.the adenine nucleotide translocator (ant) of the inner mitochondrial membrane is an autoantigen in myocarditis and in dilated cardiomyopathy. clinical and experimental studies showed that specific autoantibodies inhibit the transmembrane nucleotide transport. in isolated hearts of guinea pigs immunized with the ant, energy metabolism is disturbed. this metabolic disorder is related to functionally active specific antibodies and to a reduced heart function. this study tests whether similar immuno ...199910615393
persistence of coxsackievirus b4 infection in rhabdomyosarcoma cells for 30 months. brief report.a persistent infection of rhabdomyosarcoma (rd) cells by coxsackie b4 virus (cbv-4) was established. the persistently infected rd (pird) cells have been maintained for over 130 passages (30 months) and have released virus continuously without cellular destruction. the production of infectious virus declined three times during the study. after the first decline (third week post infection) a viral variant with a littered cytopathic effect (cpe) and a marked delayed replication cycle on green monke ...199910603178
selenium and host defence towards viruses.the association between viral disease and nutrition has long been thought to be due to effects on the host immune system. this theory suggests that when a host is malnourished, the immune system is compromised, and thus increased susceptibility to viral infection will occur. however, the virus itself may also be affected by the nutritional status of the host. we have demonstrated that a normally-benign strain of coxsackievirus b3 (cvb3/0) becomes virulent in either se-deficient or vitamin e-defi ...199910604206
a new picornavirus isolated from bank voles (clethrionomys glareolus).a previously unknown picornavirus was isolated from bank voles (clethrionomys glareolus). electron microscopy images and sequence data of the prototype isolate, named ljungan virus, showed that it is a picornavirus. the amino acid sequences of predicted ljungan virus capsid proteins vp2 and vp3 were closely related to the human pathogen echovirus 22 (approximately 70% similarity). a partial 5' noncoding region sequence of ljungan virus showed the highest degree of relatedness to cardioviruses. t ...199910049824
identification of neutralizing epitopes on a european strain of swine vesicular disease virus.six neutralizing monoclonal antibodies (mabs) were used to isolate mab neutralization-resistant (mar) mutants from a recent european strain of swine vesicular disease virus (svdv), itl/9/93. sequencing of mar mutants identified two epitopes located at positions analogous to sites 2a (vp2) and 3b (vp3) on poliovirus (pv) which have been previously identified on a japanese strain of svdv. a third epitope near to the c terminus of vp1, not previously recognized on svdv, was tentatively identified i ...199910073685
serum albumin inhibits echovirus 7 uncoating.echoviruses induce a wide spectrum of diseases in man, the most severe being meningitis. in neonates, however, a severe systemic infection can be observed, leading to death. serum albumin is the most abundant protein in plasma and most interstitial fluids, and its functions include osmoregulation and transport and delivery of hydrophobic molecules such as fatty acids and steroids. the results of cold-synchronized one-step growth analysis of echovirus 7 infection and sucrose-gradient analysis of ...199910073686
genomic and phylogenetic characterization of coxsackievirus b2 prototype strain ohio-1.the human picornavirus coxsackievirus b2 (cvb2) is often linked to several infections, from mild respiratory diseases to more severe illnesses such as myocarditis. in this study, we report the complete genome sequence of cvb2 prototype strain ohio-1. the genome sequence was determined from reverse transcribed viral rna, amplified with long distance pcr and used for non-radioactive sequencing. the full length pcr amplicons were used for in vitro transcription and the obtained crna was lipofected ...199910082394
molecular evolution of swine vesicular disease virus.phylogenetic analysis was used to examine the evolutionary relationships within a group of coxsackie b viruses that contained representatives of the major serotypes of this group and 45 isolates of swine vesicular disease virus (svdv) from asia and europe. separate analyses of sequence data from two regions of the viral genomes encoding the vp1 and 3bc genes both revealed that the svdv belonged to a single monophyletic group which could be clearly distinguished from all other sampled coxsackievi ...199910092004
cleavage of rasgap and phosphorylation of mitogen-activated protein kinase in the course of coxsackievirus b3 replication.recently, we reported on tyrosine phosphorylation of distinct cellular proteins in the course of enterovirus infections (m. huber, h.-c. selinka, and r. kandolf, j. virol. 71:595-600, 1997). these phosphorylation events were mediated by src-like kinases and were shown to be necessary for effective virus replication. that study is now extended by examination of the interaction of the adapter protein sam68, a cellular target of src-like kinases which has been shown to interact with the poliovirus ...199910196249
[efficacy of immunized milk for preventing viral infection].this paper investigated the efficacy of passive protection provided by milk (immunized milk) against enterovirus infection in mice experimentally infected with enterovirus. milk with a high antibody titer against six enterovirus serotypes was prepared from hyperimmunized goat. in vivo and in vitro experiments were performed and the results showed that immunized milk has an antiviral activity against enterovirus infection. further observation was performed using coxsackie b 3 virus (cvb 3). when ...199910213988
[an epidemic of aseptic meningitis caused by echoviruses in fukuoka prefecture during april 1997 to august 1998].an epidemic of aseptic meningitis in fukuoka prefecture during april 1997 to august 1998 was studied to determine the serotype of viruses isolated in fukuoka prefecture. in fukuoka prefecture, bimodal peaks were seen in july and december 1997. monthly changes of reported aseptic meningitis patients and period of virus isolation revealed that epidemics of the earlier part in 1997 was caused by echovirus 9 (e 9) and the latter part due to echovirus 30 (e 30). e 9 was isolated mainly in chikugo are ...199910213990
characterization of anti-heart antibodies in mice after infection with coxsackie b3 virus.coxsackie virus b3 (cvb3) infection results in a marked inflammatory response and the production of autoantibodies to cardiac antigens, with cardiac myosin heavy chain documented to be the most immunogenic antigen. the present study investigated the temporal appearance of anti-heart antibodies in mice after mock infection or infection with an attenuated variant of cvb3 or wildtype cvb3 by sds-page and western blotting. further characterization of the autoantigens was carried out using 2d electro ...199910219259
coxsackievirus b3-induced myocarditis in mhc class ii-deficient mice.the pathogenesis of coxsackievirus b3 (cvb3)-induced myocarditis was investigated in immunocompetent c57bl/6 and mhc class ii knockout mice with identical genetic backgrounds.199910225212
attenuated virulence of pleconaril-resistant coxsackievirus b3 variants.pleconaril (vp 63843) is a novel orally bioavailable small molecule with broad antipicornavirus (enterovirus and rhinovirus) activity. ten independently derived pleconaril-resistant variants of coxsackievirus b3 were isolated from cell culture. the molecular basis of drug resistance and the biologic properties of the drug-resistant viruses were investigated. rna sequence analysis revealed amino acid changes in the drug-binding pocket of the resistant variants. thermal stability studies showed th ...199910228078
specific detection of echoviruses 22 and 23 in cell culture supernatants by rt-pcr.reverse transcription-polymerase chain reaction (rt-pcr) methods are available for the rapid detection of enteroviruses in clinical specimens or virus isolates. pan-enterovirus pcr primers, however, fail to amplify echovirus (e) type 22 or 23 because of their extreme sequence divergence from the other enteroviruses. we have developed an rt-pcr method to detect specifically e22 and e23 rna directly in tissue culture supernatants without a viral rna purification step. the e22/e23 primers successfu ...199910335867
gamma delta+ t cells regulate major histocompatibility complex class ii(ia and ie)-dependent susceptibility to coxsackievirus b3-induced autoimmune myocarditis.coxsackievirus b3 (cvb3) infection induces myocardial inflammation and myocyte necrosis in some, but not all, strains of mice. c57bl/6 mice, which inherently lack major histocompatibility complex (mhc) class ii ie antigen, develop minimal cardiac lesions despite high levels of virus in the heart. the present experiments evaluate the relative roles of class ii ia and ie expression on myocarditis susceptibility in four transgenic c57bl/6 mouse strains differing in mhc class ii antigen expression. ...199910364312
a new variant of echovirus 4 associated with a large outbreak of aseptic meningitis.a large outbreak of aseptic meningitis which began in april 1997 involved hundreds of cases in all geographical regions of israel and the palestinian authority, peaked between june and september, and lasted until december.199910405889
[the use of the natural mineral saponite for water decontamination].sorption properties were studied of natural and activated specimens of saponite with respect to poliomyelitis virus, coxsackie b 1 and b 6 viruses as well as to enterobacteriaceae group bacteria. with the purpose of comparing the processes of sorption of microorganisms, other minerals were also used, such as bentonite, alunite, glauconite, ceolite. the natural saponite adsorptive properties were found out to undergo changes during the process of thermoactivation. mechanisms are discussed of a de ...199910423991
[gene transfer efficiency enhancement by inactivated coxsakie virus b1 in primary skeletal muscle cells].to study the effect of inactivated coxsackie virus b1(cvb1), which was considered to have high affinity to skeletal muscle cell, on gene transfer efficiency of reporter gene, pcdna3-lacz, in primary muscle cells.199910431055
laboratory-scale inactivation of african swine fever virus and swine vesicular disease virus in pig slurry.two methods were evaluated for the inactivation of african swine fever (asv) and swine vesicular disease (svd) viruses in pig slurry: chemical treatment and heat treatment. the addition of naoh or ca(oh)2 at different concentration/time combinations at 4 degrees c and 22 degrees c was examined, as was virus stability at different temperature/time combinations. asf virus (asfv) was less resistant to both methods than svd virus (svdv). in slurry from one source, asfv was inactivated at 65 degrees ...199910432596
picornavirus receptor down-regulation by plasminogen activator inhibitor type 2.therapeutic interference with virus-cell surface receptor interactions represents a viable antiviral strategy. here we demonstrate that cytoplasmic expression of the serine protease inhibitor (serpin), plasminogen activator inhibitor type 2 (pai-2), affords a high level of protection from lytic infection by multiple human picornaviruses. the antiviral action of pai-2 was mediated primarily through transcriptional down-regulation of the following virus receptors: intercellular adhesion molecule 1 ...199910438806
expression of tumour necrosis factor (tnf) receptor/ligand superfamily co-stimulatory molecules cd40, cd30l, cd27l, and ox40l in murine hearts with chronic ongoing myocarditis caused by coxsackie virus b3.t-cell-mediated myocardial damage has been shown to be involved in acute myocarditis and dilated cardiomyopathy. it is necessary for t-cells to receive a co-stimulatory signal as well as the main signal through the t-cell receptor for antigen-specific t-cell activation to occur. to investigate the roles of the co-stimulatory molecules cd40/cd40l, cd30/cd30l, cd27/cd27l, and ox40/ox40l, which belong to the tumour necrosis factor (tnf) receptor/ligand superfamily, in the development of chronic ong ...199910440754
induction of myocardial nitric oxide synthase by coxsackie b3 virus in mice.inducible nitric oxide synthase (inos) expression is regulated by cytokines. this study investigated whether coxsackie group b virus (cvb) myocarditis resulted in an environment suitable for induction of nos in the murine heart.199910457155
analysis of antibody responses against coxsackie virus b4 protein 2c and the diabetes autoantigen gad(65).type i diabetes mellitus results from the autoimmune destruction of insulin producing beta cells in the pancreas. certain viral infections, especially those caused by coxsackie b viruses and related enteroviruses, have been associated with the development of type i diabetes. the sequence homology between the coxsackie b4 virus nonstructural protein 2c (cvb4 p2c) and the major diabetes autoantigen glutamic acid decarboxylase (gad(65)) provides a basis for the hypothesis of molecular mimicry. in t ...199910459165
a novel serological technique: polymerase chain reaction enhanced immunoassay. application to enterovirus igm diagnosis.the polymerase chain reaction (pcr) method is a sensitive, specific and rapid technique for virus detection. the principles of a pcr enhanced immunoassay (pia) are described. the method combines solid phase serological techniques with the pcr, providing a versatile and sensitive method for antibody detection. by linking the antigenicity of virus particles with their content of nucleic acid, the method provides new possibilities for virus serology: for example, antibody specificity can be coupled ...199910471028
coxsackievirus b4 myocarditis in an orangutan.a 37-year-old female orangutan died at the zoological garden. autopsy examination demonstrated severe coxsackievirus b4 myocarditis immunohistochemically as a cause of the death. apoptosis of the cardiac muscle cells was observed using the tdt-mediated dutp-biotin nick endo labeling method and was considered to play a role in the myocarditis. congestion of the liver and both lungs due to cardiac failure was also observed. coxsackievirus infection is found frequently in the okinawan human populat ...199910490214
synthesis and antiviral activity of some n-benzenesulphonylbenzimidazoles.some n-sulphonylated benzimidazoles were synthesized as potential antiviral agents. compound 16b and, to a lesser extent, 19b showed activity against two rna viruses at micromolar concentrations.199910498201
the complete consensus sequence of coxsackievirus b6 and generation of infectious clones by long rt-pcr.the full length sequence for the human pathogen coxsackievirus b6 (cvb6, schmitt strain) has been determined. we used long rt-pcr to generate full length dna amplicon of cvb6, and then directly sequenced the amplicons. one-step cloning of the full length amplicon enabled us to obtain an infectious clone of cvb6. rna generated from cvb6 amplicon dna or cvb6 clones, by transcription with t7 rna polymerase, was demonstrated to be infectious upon transfection into hela cells in vitro. the cvb6 genom ...199910500285
functional features of the bovine enterovirus 5'-non-translated region.the bovine enterovirus (bev) serotypes exhibit unique features of the non-translated regions (ntrs) which separate them from the other enteroviruses. their most remarkable property is an additional genome region of 110 nt located between the 5'-cloverleaf and the internal ribosome entry site (ires). this genome region has the potential to form an additional cloverleaf structure (domain i*) separated from the 5'-cloverleaf (domain i) by a small stem-loop (domain i**). other characteristics involv ...199910501480
mechanisms and consequences of enterovirus persistence in cardiac myocytes and cells of the immune system.in humans and experimental murine models enteroviruses, and in particular coxsackieviruses of group b (cvb), may induce chronic myocarditis associated with a persistent type of heart muscle infection. persistent myocardial infection has been characterized by restricted viral replication and gene expression, which is capable of sustaining chronic inflammation. altered replication and transcription of the virus, in addition to an immune response insufficient to recognize and clear infected cells e ...199910507324
the role of b lymphocytes in coxsackievirus b3 infection.coxsackieviruses are important human pathogens, frequently causing myocarditis, pancreatitis, and a variety of less severe diseases. b lymphocytes appear central to the interaction between these viruses and their mammalian hosts, because agammaglobulinemic humans, genetically incapable of antibody production, are susceptible to chronic infections by coxsackieviruses and related enteroviruses, such as poliovirus and echovirus. however, recent studies show that type b coxsackievirus (cvb) infects ...199910514403
requirements for rna replication of a poliovirus replicon by coxsackievirus b3 rna polymerase.a chimeric poliovirus type 1 (pv1) genome was constructed in which the 3d rna polymerase (3d(pol)) coding sequences were replaced with those from coxsackievirus b3 (cvb3). no infectious virus was produced from hela cells transfected with the chimeric rna. processing of the pv1 capsid protein precursor was incomplete, presumably due to inefficient recognition of the p1 protein substrate by the chimeric 3cd proteinase containing cvb3 3d sequences. the ability of the chimeric rna to replicate in th ...199910516050
synthesis and antiviral and antineoplastic activities of some novel carbocyclic guanosine analogues with a cyclobutane ring.cyclobutyl nucleoside analogues containing guanine and 8-azaguanine (compounds 5-10) were prepared from (1r,cis)-3-aminomethyl-2,2-dimethylcyclobutylmethanol (1). all were evaluated as antiviral and antitumoral agents in a variety of assay systems. compounds 6 and 7 showed a noteworthy activity against a respiratory syncytial virus and compound 10 was moderately active against vaccinia virus. only compound 5 showed some cytostatic activity.199910517011
genomic organization and chromosomal localization of the human coxsackievirus b-adenovirus receptor gene.myocarditis and dilated cardiomyopathy (dcm) are common causes of morbidity and mortality in children. many studies have implicated the enteroviruses and, particularly, the coxsackievirus-b family as etiologic agents of the acquired forms of these diseases. however, we have shown the group-c adenoviruses to be as commonly detected as enteroviruses in the myocardium of children and adults with these diseases. it has remained something of a conundrum why two such divergent virus families cause the ...199910543405
molecular mechanisms of coxsackievirus persistence in chronic inflammatory myopathy: viral rna persists through formation of a double-stranded complex without associated genomic mutations or evolution.enterovirus infection and persistence have been implicated in the pathogenesis of certain chronic muscle diseases. in vitro studies suggest that persistent enteroviruses mutate, evolving into forms that are less lytic and display altered tropism, but it is less clear whether these mechanisms operate in vivo. in this study, persistent coxsackievirus rna from the muscle of mice afflicted with chronic inflammatory myopathy (cim) was characterized and compared with rna from a virus that had establis ...199910559326
comparative analysis of virus-host cell interactions of haemagglutinating and non-haemagglutinating strains of coxsackievirus b3.decay-accelerating factor (daf/cd55), and coxsackievirus-adenovirus receptor (car) have been identified as cellular receptors for coxsackie b viruses (cbv). to elucidate the interplay of daf and car on the cell surface, virus-receptor interactions of two coxsackieviruses of serotype b3 (non-haemagglutinating cbv3 and haemagglutinating cbv3-ha strain) were analysed. binding assays revealed clear differences between these viruses with regard to their interactions with daf and car. however, only th ...199910567646
structural requirements of the higher order rna kissing element in the enteroviral 3'utr.the origin of replication ( orir ) involved in the initiation of (-) strand enterovirus rna synthesis is a quasi-globular multi-domain rna structure which is maintained by a tertiary kissing interaction. the kissing interaction is formed by base pairing of complementary sequences within the predominant hairpin-loop structures of the enteroviral 3' untranslated region. in this report, we have fully characterised the kissing interaction. site-directed mutations which affected the different base pa ...19999862969
coxsackievirus and adenovirus receptor amino-terminal immunoglobulin v-related domain binds adenovirus type 2 and fiber knob from adenovirus type 12.the extracellular region of the coxsackievirus and adenovirus receptor (car) is predicted to consist of two immunoglobulin (ig)-related structural domains. we expressed the isolated car amino-terminal domain (d1) and a car fragment containing both extracellular ig domains (d1/d2) in escherichia coli. both d1 and d1/d2 formed complexes in vitro with the recombinant knob domain of adenovirus type 12 (ad12) fiber, and d1 inhibited adenovirus type 2 (ad2) infection of hela cells. these results indic ...19999882344
cold pressure test producing coronary spasm, coronary thrombosis and myocardial infarction in a patient with igm antibodies against coxsackie b virus.several lines of evidence have shown that viral infections are capable of causing coronary spasm and precipitating or mimicking clinical myocardial infarction. here we report the case of a 41-year-old woman with recurrent angina who was admitted to our hospital because of ventricular tachycardia. laboratory examination revealed positive igm titers against coxsackie b virus. coronary angiography showed normal coronary arteries, but following a cold pressure test severe spasm of all coronaries wit ...199910844390
an outbreak of aseptic meningitis due to echo 30 virus in romania during the 1999 summer.between april-september 1999 an unusually high number of acute aseptic meningitis was reported in six north eastern counties of romania. at the end of 1999 summer the epidemic area extended in south romania including the capital city bucharest. the total number of cases surpassed 5500. the majority of confirmed cases were young children under 15 years of age. more than 1800 cases were registered in the same interval in the neighboring republic of moldavia. we report the isolation of echo 30 viru ...199911601385
[protective and therapeutic effects of intravenous-immunoglobulin on viral myocarditis].this study was conducted to determine whether the administration of domestically manufactured intravenous-immunoglobulin (ivig) could prevent or alleviate myocarditis in mice. male balb/c mice were randomized into two groups for protection group (p) and therapy group (t), and each of the two groups was subdivided into 4 groups (1, 2, 3 and c). a 7-day protocol with daily ivig dosage of 200 mg/kg, 500 mg/kg and 1 g/kg for groups, p1, t1, p2, t2 and p3, t3 respectively was designed. in the experim ...199912205932
[study on combined clinical manifestation and myocardial perfusion imaging with 99mtc-mibi spect for diagnosing myocarditis].in 568 cases suffering from upper-respiratory tract infection with sore throat and more than one of following clinical manifestations: arrhythmia, heart failure and chest pain or oppressive sensation over the chest(group a), and another 108 cases without above clinical manifestations(group b), myocardial perfusion imaging with 99mtc-mibi spect was studied. the results revealed that the imaging in 404 cases (71.12%) of group a supported diagnosis of myocarditis, but only 6 cases(5.56%) did so in ...199912080657
rt-pcr and cell culture infectivity assay to detect enteroviruses during drinking water treatment processes.in this study, 62 water samples were collected from two water treatment plants (wtps) in suez canal cities (port said and ismaillia) and one plant in cairo (giza wtp) in addition to the beginning of the two nile river branches (rosetta and damietta). viruses were concentrated by adsorption-elution ethod sing 142 mm-diameter nitrocellulose membrane of 0.45 microm pore size and eluted with 3% beef extract at ph 9.5. the concentrated samples were inoculated for 3 successive passages in three cell c ...199917219867
[experimental study on inhibitory effect of ganlu xiaodu dan on coxackie virus in vitro].to observe the coxackie virus inhibitory effect of ganlu xiaodu dan (glxdd), including complete recipe, incomplete recipe and supplemented recipe of it.199811475722
[experimental study on treatment of viral myocarditis in mice by integrated traditional chinese and western medicine].to clarify the effects of astragalus membranaceus (am) combined with taurine and/or coenzyme q10(coq10) on coxsackievirus b3 (cvb3) murine myocarditis.199811477833
[experimental study on therapeutical effect of chinese medicine on polymyositis in guinea pigs].to study the therapeutical effects of radix bupleuri and ramulus cinnamomi on virus polymyositis in guinea pigs.199811477912
coxsackie b virus infection and myopericarditis in thailand, 1987-1989.serum specimens of 363 myopericarditis patients from the hospital all over the country were examined for coxsackie b virus antibody during 1987-1989 by means of microneutralization test in order to assess association between myopericarditis and coxsackie b virus infection. the data established that certain virus infection rates were 24.3%, 19.4% and 23.6% respectively, no differences in incidence were found between sex (p > 0.05) and the incidence rate between age groups below 15 years and 15 ye ...19989886111
epidemics of aseptic meningitis due to enteroviruses following national immunization days in bahrain.we report two successive epidemics of aseptic meningitis due to enteroviruses (ev) observed after national immunization days against polio. meningitis due to echovirus 30 occurred from july 1995 to the end of january 1996, mostly among children aged 0-12 years (95.1% of cases), and meningitis due to echovirus 4 occurred from may 1996 to the end of september 1996 in the same age group. there were 286 and 169 cases, respectively. specimens from several representative cases were sent to the who col ...19989924570
[is infection with group a streptococcus the only reason for rheumatic fever?--a case report of rheumatic fever coexisting with coxsackie b1 virus infection].the course of rheumatic fever in 11 years old boy is described. the significance of cellular immunity in rheumatic fever pathogenesis and the importance of virus infection coexistence is emphasized in discussion.199810021888
echovirus keratoconjunctivitis.to investigate an outbreak of echovirus-related keratoconjunctivitis.19989467445
the role of inducible nitric oxide synthase in the host response to coxsackievirus myocarditis.the host response to coxsackievirus infection is complex, including t lymphocytes, b lymphocytes, natural killer cells, and macrophages. although coxsackievirus infection induces expression of inducible nitric oxide synthase (nos2; ec 1.14.13.39) in macrophages, the precise role of nos2 in the host response to coxsackievirus myocarditis has been unclear. we show, by using mice homozygous for a disrupted nos2 allele, that coxsackievirus replicates to higher titers in nos2(-/-) mice, that the host ...19989482909
antiviral activity of win 54954 in coxsackievirus b2 carrier state infected human myocardial fibroblasts.persistent infections with a cardiotropic enterovirus, e.g. coxsackievirus b2 (cvb2), cause chronic myocarditis and eventually congestive heart failure. therefore, the antiviral activity of win 54954, a capsid binding antiviral agent that inhibits enterovirus uncoating, was studied in persistently cvb2-infected cultures of human myocardial fibroblasts. cultures displayed a typical carrier state infection with virus titers of 3.9 +/- 1.6 x 10(5) plaque forming units (pfu)/ml and 0.99% infected ce ...19989497072
molecular mimicry in diabetes mellitus: the homologous domain in coxsackie b virus protein 2c and islet autoantigen gad65 is highly conserved in the coxsackie b-like enteroviruses and binds to the diabetes associated hla-dr3 molecule.it has been proposed that molecular mimicry between protein 2c (p2c) of coxsackie virus b4 and the autoantigen glutamic acid decarboxylase (gad65) plays a role in the pathogenesis of insulin-dependent diabetes mellitus (iddm). in this study we show that the amino acid sequence of p2c which shares homology with a sequence in gad65 (pevkek), is highly conserved in coxsackie virus b4 isolates as well as in different viruses of the subgroup of coxsackie b-like enteroviruses. these are the most preva ...19989498628
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