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cutting edge: antibody-mediated tlr7-dependent recognition of viral rna.tlr7 recognizes the genome of ssrna viruses such as coxsackievirus b. because tlr7 is expressed in intracellular compartments, viral rna must be internalized before its recognition by tlr7. in this study, we define plasmacytoid dendritic cells (pdc) as peripheral blood mononuclear immune cells that respond to coxsackievirus. pdc activation by coxsackievirus b requires the presence of specific antiviral abs. we show that fc receptors mediate the recognition of virus-ab complexes and that tlr7 is ...200717339429
tlr ligands act directly upon t cells to restore proliferation in the absence of protein kinase c-theta signaling and promote autoimmune myocarditis.the serine/threonine kinase, protein kinase c-theta (pkc-theta), plays a central role in the activation and differentiation of th2 cells while being redundant in cd4+ and cd8+ antiviral responses. recent evidence indicates that pkc-theta may however be required for some t cell-driven autoimmune responses. we have investigated the role of pkc-theta in the induction of autoimmune myocarditis induced by either coxsackie b3 virus infection or immunization with alpha-myosin/cfa (experimental autoimmu ...200717339441
[cytomorphology and enzymocytochemistry of coxsackie virus a9 infection in cell cultures]. 196917340839
specific interaction of hela cell proteins with coxsackievirus b3 3'utr: la autoantigen binds the 3' and 5'utr independently of the poly(a) tail.coxsackievirus b3 (cvb3) is a positive, single-stranded rna virus. the secondary structure of the 3' untranslated region (3'utr) of cvb3 rna consists of three stem-loops and is followed by a poly(a) tail sequence. these stem-loop structures have been suggested to participate in the regulation of viral replication through interaction with cellular proteins that are yet to be identified. in this study, by competitive uv cross-linking using mutated 3'utr probes we have demonstrated that the poly(a) ...200717346312
change in the cells that express connective tissue growth factor in acute coxsackievirus-induced myocardial fibrosis in mouse.cardiac fibrosis and inflammation are major pathologic conditions that result from viral myocarditis. connective tissue growth factor (ctgf) stimulates fibroblast proliferation and induces production of extracellular matrix molecules. we studied the correlation between ctgf and cardiac fibrosis in an acute coxsackievirus b3 (cvb3) myocarditis animal model. eight-week-old balb/c mice were infected intraperitoneally with 10(4) plaque forming units (pfu) of cvb3. myocardial inflammation peaked on d ...200717350707
inhibitor of nf kappa b alpha is a host sensor of coxsackievirus infection.apoptosis is a host response to viral infection: programmed cell death can limit viral replication. therefore, the knowledge of pathways by which cells detect viral infection and activate apoptosis may be of considerable interest when developing strategies against viral pathogens. we have shown that cells activate apoptosis in response to coxsackievirus b3 (cvb3) infection. in an effort to discover how cells detect viral infections, we found that the viral protease 3c(pro) cleaves ikappabalpha. ...200717351338
antiviral triterpenoids from the medicinal plant schefflera heptaphylla.schefflera heptaphylla (l.) frodin is a principal ingredient of an herbal tea formulation widely used for the treatment of common cold in southern china. an extract of the long leafstalk of the compound leaf of s. heptaphylla exhibited the most potent antiviral activity against respiratory syncytial virus (rsv). further antiviral-guided fractionation and isolation of the leafstalk extract of s. heptaphylla led to obtain two highly active pure triterpenoids, namely 3alpha-hydroxylup-20(29)-ene-23 ...200717357972
pdtc inhibits picornavirus polyprotein processing and rna replication by transporting zinc ions into cells.previously, it was shown that pyrrolidine dithiocarbamate (pdtc) inhibits proteolytic polyprotein processing and replication of human rhinovirus by transporting metal ions into cells. here, it is shown that pdtc also inhibits replication of two other picornaviruses: coxsackievirus b3 (cvb3), a closely related virus that belongs to the genus enterovirus, and mengovirus, an encephalomyocarditis virus strain that belongs to the genus cardiovirus, and that this inhibition is due to the dithiocarbama ...200717374764
coxsackievirus infections and nod mice: relevant models of protection from, and induction of, type 1 diabetes.human enteroviruses (hevs) like the group b coxsackieviruses (cvbs) are prime candidates for infectious, environmental causes of human type 1 diabetes (t1d). non-obese diabetic (nod) female mice are well protected from t1d onset if inoculated with cvb when young. older, prediabetic nod mice can rapidly develop t1d following inoculation with cvb, mimicking clinical reports of disease-associated t1d onset. the ability to induce rapid t1d in nod mice is linked to the rate of replication of the cvb ...200717376828
coxsackievirus b3 and adenovirus infections of cardiac cells are efficiently inhibited by vector-mediated rna interference targeting their common receptor.as coxsackievirus b3 (coxb3) and adenoviruses may cause acute myocarditis and inflammatory cardiomyopathy, isolation of the common coxsackievirus-adenovirus-receptor (car) has provided an interesting new target for molecular antiviral therapy. whereas many viruses show high mutation rates enabling them to develop escape mutants, mutations of their cellular virus receptors are far less likely. we report on antiviral efficacies of car gene silencing by short hairpin (sh)rnas in the cardiac-derived ...200717377597
cerebrospinal fluid cytokines in enterovirus 71 brain stem encephalitis and echovirus meningitis infections of varying severity.taiwan has experienced several outbreaks of enterovirus 71 (ev71) infections since 1998. this study examined the quantitative relationship between specific cytokines in the cerebrospinal fluid (csf) and the severity of ev71 brain stem encephalitis (be), and investigated whether the csf cytokine response differed from that to uncomplicated echovirus meningitis (em). the study included 57 children with ev71 be, of whom 24 had isolated be, 24 had autonomic nervous system (ans) dysregulation, and ni ...200717441979
coxsackievirus b3 proteins directionally complement each other to downregulate surface major histocompatibility complex class i.picornaviruses carry a small number of proteins with diverse functions that subvert and exploit the host cell. we have previously shown that three coxsackievirus b3 (cvb3) proteins (2b, 2bc, and 3a) target the golgi complex and inhibit protein transit. here we investigate these effects in more detail and evaluate the distribution of major histocompatibility complex (mhc) class i molecules, which are critical mediators of the cd8(+) t-cell response. we report that concomitant with viral protein s ...200717442717
microarray-based molecular detection of foot-and-mouth disease, vesicular stomatitis and swine vesicular disease viruses, using padlock probes.the world organization for animal health (office international des epizooties, oie) includes the diseases caused by foot-and-mouth disease virus (fmdv), swine vesicular disease virus (svdv), and vesicular stomatitis virus (vsv), as "diseases notifiable to the oie". foot-and-mouth disease (fmd) outbreaks have severe economical as well as social effects and cannot be differentiated from the diseases caused by the other two viruses on the basis of clinical symptoms. efficient laboratory techniques ...200717451815
[epidemiological surveillance for viral pollution of rivers in toyama prefecture].virus pollution of three rivers in toyama prefecture was surveyed over a long period in order to predict and to prevent water-born infection.200717461029
virus induces metal-binding proteins and changed trace element balance in the brain during the course of a common human infection (coxsackievirus b3) in mice.autopsy of the brain has shown a change in trace element balance in some virus-infected individuals, but it is not known whether this event was a result of the infection. in the present study coxsackievirus b3 (cvb3) adapted to balb/c mice was used to study whether infection induces gene expression of the metal-binding/transporting proteins metallothionein (mt1 and mt3) and divalent-metal transporter 1 (dmt1) and whether it changes the balance of trace elements in the brain. virus and mt1, mt3, ...200717467775
coxsackie virus b1 infection in a child, complicated by severe oliguric renal failure. 200717474564
molecular identification of 13 new enterovirus types, ev79-88, ev97, and ev100-101, members of the species human enterovirus b.molecular methods have enabled the rapid identification of new enterovirus (ev) serotypes that are untypeable using existing neutralizing antisera. as a result, sequencing of the vp1 capsid gene has been developed as a surrogate for antigenic typing to distinguish enterovirus types. in this study, 17 enterovirus isolates from four countries were identified as members of 13 new types within the species human enterovirus b (hev-b) by complete genome sequencing. members of each of these new types a ...200717485128
human pancreatic islet endothelial cells express coxsackievirus and adenovirus receptor and are activated by coxsackie b virus infection.enteroviruses, such as the coxsackievirus (cv) group, have been linked to the induction of inflammatory and autoimmune diseases. virus tropism and tissue access are modulated by endothelial cells. to examine the susceptibility of microvascular endothelial cells (mecs) derived from pancreatic islets to infection with cv group b (cvb), purified cultured human islet mecs were infected with cvb-4 strain, and the immunological phenotype of the infected cells was analyzed. cvb-4 persistently infected ...200717494992
antiviral activity of arbidol against influenza a virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo.arbidol, ethyl-6-bromo-4-[(dimethylamino)-methyl]-5-hydroxy-1-methyl-2-[(phenylthio)methyl]-in dole-3-carboxylate hydrochloride monohydrate, is an antiviral chemical agent. in this report, we studied the antiviral activity of arbidol against a panel of human respiratory viruses, namely influenza a virus (flu-a, a/pr/8/34 h1n1), respiratory syncytial virus (rsv), human rhinovirus type 14 (hrv 14), coxsackie virus b3 (cvb3) and adenovirus type 7 (adv-7) in vitro in cell culture. arbidol was found ...200717497238
[th cell differentiation in chronic stage of viral myocarditis in mice and interference of qingxin-ii recipe].to investigate part mechanisms of th cell differentiation, and to observe the interference effect of qingxin-ii recipe in the chronic stage of viral myocarditis (vmc), so as to provide some experimental evidences for illuminating the pathogenesis of vmc and treatment mechanisms of qingxin-ii recipe.200717498494
cutting edge: cross-regulation by tlr4 and t cell ig mucin-3 determines sex differences in inflammatory heart disease.recent clinical studies have reinforced the importance of sex-related differences in the pathogenesis of cardiovascular diseases, with an increased incidence and mortality in men. similar to humans, male balb/c mice infected with coxsackievirus b3 (cvb3) develop more severe inflammation in the heart even though viral replication is no greater than in females. we show that tlr4 and ifn-gamma levels are significantly elevated and regulatory t cell (treg) populations significantly reduced in the he ...200717513715
genetic and phenotypic diversity of echovirus 30 strains and pathogenesis of type 1 diabetes.several enterovirus serotypes should be considered as potentially diabetogenic. the capacity of an enterovirus to kill or impair the functions of human beta-cells can vary among the strains within a given serotype as shown previously for echovirus 9 and 30 (e-30). the evolution of e-30 has also shown patterns correlating with the global increase of type 1 diabetes incidence. in the present study, antigenic properties of a set of e-30 isolates were investigated and the results correlated with the ...200717516516
genetic adaptation to untranslated region-mediated enterovirus growth deficits by mutations in the nonstructural proteins 3ab and 3cd.both untranslated regions (utrs) of plus-strand rna virus genomes jointly control translation and replication of viral genomes. in the case of the enterovirus genus of the picornaviridae family, the 5'utr consists of a cloverleaf-like terminus preceding the internal ribosomal entry site (ires) and the 3' terminus is composed of a structured 3'utr and poly(a). the ires and poly(a) have been implicated in translation control, and all utr structures, in addition to cis-acting genetic elements mappi ...200717537861
natural recombination event within the capsid genomic region leading to a chimeric strain of human enterovirus b.recombination between two strains is a known phenomenon for enteroviruses replicating within a single cell. we describe a recombinant strain recovered from human stools, typed as coxsackievirus b4 (cv-b4) and cv-b3 after partial sequencing of the vp1 and vp2 coding regions, respectively. the strain was neutralized by a polyclonal cv-b3-specific antiserum but not by a cv-b4-specific antiserum. the nucleotide sequence analysis of the whole structural genomic region showed the occurrence of a recom ...200717537864
universal and mutation-resistant anti-enteroviral activity: potency of small interfering rna complementary to the conserved cis-acting replication element within the enterovirus coding region.the promising potential of rna interference-based antiviral therapies has been well established. however, the antiviral efficacy is largely limited by genomic diversity and genetic instability of various viruses, including human enterovirus b (heb). in this work, the first evidence supporting the anti-heb activity of the small interfering rna (sirna) targeting the highly conserved cis-acting replication element (cre) within virus coding region 2c is presented. hela cells pre-treated with sirna c ...200717554034
interferons induce an antiviral state in human pancreatic islet cells.enterovirus infections, in particular those with coxsackieviruses, have been linked to the development of type 1 diabetes (t1d). although animal models have demonstrated that interferons (ifns) regulate virus-induced t1d by acting directly on the beta cell, little is known on the human pancreatic islet response to ifns. here we show that human islet cells respond to ifns by expressing signature genes of antiviral defense. we also demonstrate that they express three intracellular sensors for vira ...200717559902
host-pathogen evolution: implications for the prevention and treatment of malaria, myocardial infarction and aids.humans have evolved complex immune systems to protect against infection by pathogens. however, pathogens possess a remarkable genetic versatility that allows them to gain new vigour and so escape such population immunity. conflicting pathogen-host objectives, therefore, lead to the evolutionary equivalent of an "arms race". typically, in this struggle, pathogens attempt to deplete their host of specific nutrients that are essential for immune system function. after infection, the resulting defic ...200817590522
an echovirus type 18 outbreak in a neonatal intensive care unit.we describe an outbreak of echovirus type 18 infection involving 20 neonatal intensive care unit (nicu) patients and the results of virological investigations are presented. rt-pcr demonstrated a widespread transmission of the virus in nicu patients during the outbreak. separation care and additional infection control measures seemed to be effective in preventing further spread of the virus.200817593390
coxsackievirus b3 modulates cell death by downregulating activating transcription factor 3 in hela cells.activating transcription factor 3 (atf3) is an early-induced gene involved in diverse cellular functions in response to various stresses including viral infection. here we observed marked reduction of atf3 by coxsackievirus b3 (cvb3) infection and investigated the regulation and functional role of atf3 in hela cells for the understanding of biological significance of atf3 downregulation. cvb3 infection markedly reduced atf3 expression at mrna and protein levels in parallel with p53 degradation, ...200717599613
the viral genetic background determines the outcome of coxsackievirus b3 infection in outbred nmri mice.the reasons for the different outcome of coxsackievirus b3 (cvb3)-induced heart disease in humans are not well understood. since there are no experimental data on the course of disease after infection with genetically different cvb3 in a natural variable population until now, we studied the outcome of virus infection in outbred nmri mice after inoculation of genetically different cvb3 variants. adult male mice were inoculated with seven closely related cvb3 variants. the histopathological change ...200717607777
a cpg oligodeoxynucleotide inducing anti-coxsackie b3 virus activity in human peripheral blood mononuclear cells.coxsackie b3 virus (cvb3) is the most significant pathogen causing myocarditis in humans, and antiviral therapy would be most effective in the early stages of the disease. here we provide evidence that bw001, a c-type cpg oligodeoxynucleotide, induces anti-cvb3 activity in human peripheral blood mononuclear cells (pbmcs). in parallel, we have demonstrated that bw001 induces human pbmcs to express mrnas of multiple types of interferon (ifn), including ifn-alpha, ifn-beta, ifn-omega and ifn-gamma, ...200717608709
significance of arginine 20 in the 2a protease for swine vesicular disease virus pathogenicity.pathogenic and attenuated strains of swine vesicular disease virus (svdv), an enterovirus, have been characterized previously and, by using chimeric infectious cdna clones, the key determinants of pathogenicity in pigs have been mapped to the coding region for 1d-2a. within this region, residue 20 of the 2a protease is particularly significant. inoculation of pigs with mutant viruses containing single amino acid substitutions at this residue leads to the appearance of revertants, often containin ...200717622632
the human fatty acid synthase: a new therapeutic target for coxsackievirus b3-induced diseases?coxsackievirus is linked to a large variety of severe human and animal diseases such as myocarditis. the interplay between host factors and virus components is crucial for the fate of the infected cells. however, host proteins which may play a role in coxsackievirus-induced diseases are ill-defined. two-dimensional gel electrophoresis of protein extracts obtained from coxsackievirus b3 (cvb3)-infected and uninfected hela or hepg2 cells combined with spot analysis revealed several proteins which ...200717662476
detection and identification of echovirus 7 from a child with gastro-enteritis.gastro-enteritis continues to be a significant cause of mortality in infants and young children in developing countries. some previous studies have associated echoviruses with gastroenteritis.200617685211
role of gnra motif mutations within stem-loop v of internal ribosome entry segment in coxsackievirus b3 molecular attenuation.the lengthy 5' nontranslated region of coxsackievirus b3 (cvb3) forms a highly ordered secondary structure containing an internal ribosome entry segment (ires), which plays an important role in controlling viral translation and pathogenesis. the stem-loop v (sl-v) of this ires contains a large lateral bulge loop which encompasses two conserved gnra motifs. in this study, we analyzed the effects of point mutations within the gnra motifs of the cvb3 ires. we characterized in vitro virus production ...200817693702
outbreak of coxsackie b4 arthritis among newborns and staff of a neonatal unit.we investigated an outbreak of coxsackie b4 arthritis in a neonatal unit involving 20 neonates and 12 staff members, over an eight-month period. laboratory investigations, serology tests, indicate that the outbreak was caused by coxsackie b4 virus. contamination of one of the overhead water reservoirs, supplying the nursery, was responsible. after the water tanks were cleaned out, no new cases were reported over five years.200717716519
development of a novel recombinant encapsidated rna particle: evaluation as an internal control for diagnostic rt-pcr.this report describes the generation of novel encapsidated rna particles and their evaluation as in-tube internal controls in diagnostic real-time reverse-transcription pcr (rrt-pcr) assays for the detection of rna viruses. a cassette containing sequences of 2 diagnostic primer sets for foot-and-mouth disease virus (fmdv) and a set for swine vesicular disease virus (svdv) was engineered into a full-length cdna clone containing the rna-2 segment of cowpea mosaic virus (cpmv). after co-inoculation ...200717727966
interaction of decay-accelerating factor with coxsackievirus b3.many entero-, parecho-, and rhinoviruses use immunoglobulin (ig)-like receptors that bind into the viral canyon and are required to initiate viral uncoating during infection. however, some of these viruses use an alternative or additional receptor that binds outside the canyon. both the coxsackievirus-adenovirus receptor (car), an ig-like molecule that binds into the viral canyon, and decay-accelerating factor (daf) have been identified as cellular receptors for coxsackievirus b3 (cvb3). a cryoe ...200717804498
the substitution u475 --> c with sabin3-like mutation within the ires attenuate coxsackievirus b3 cardiovirulence.the sabin3 mutation in the viral rna plays an important role in directing attenuation phenotype of sabin vaccine strain of poliovirus type 1 (pv1). we previously described that sabin3-like mutation introduced in coxsackievirus b3 (cvb3) genome led to a defective mutant. however, this mutation do not led to destruction of secondary structure motif c within the stem-loop v of cvb3 rna because of the presence of one nucleotide difference (c --> u) in the region encompassing the sabin3 mutation at n ...200717827538
coxsackievirus b3 activates nuclear factor kappa b transcription factor via a phosphatidylinositol-3 kinase/protein kinase b-dependent pathway to improve host cell viability.coxsackievirus b3 (cvb3) is the most common viral infectant of heart muscle. cvb3 directly injures cardiomyocytes. we have previously reported on a regulatory role for the phosphatidylinositol-3 kinase (pi3k)/protein kinase b (akt) pathway during cvb3 infection. yet, the mechanism underlying this regulatory role has not been elucidated. the pi3k/akt pathway is involved in various cellular processes and exerts its function through the activation of several downstream effectors. among them, nuclea ...200717848167
[study on the molecular typing and epidemiology of non-polio enteroviruses isolated from yunnan province, china].this report presented an overview on the epidemiology of enterovirus in yunnan province, the people's republic of china.200717850701
1a and 3d gene sequences of coxsackievirus b3 strain cc: variation and phylogenetic analysis.coxsackievirus b3 (cvb3) was thought to be the most common causative agent of life-threatening viral myocarditis. coxsackievirus b3 strain cc (cvb3-cc) was isolated in china; however, no sequence data are available. the 1a and 3d regions of cvb3-cc were sequenced and phylogenetic analysis was done with reference to ten other cvb3 strains and all 36 prototype strains of human enterovirus b (hev-b). sequence analysis showed that the 1a gene region of cvb3-cc consisted of 207 nucleotides, encoding ...200817852360
rt-pcr for confirmation of echovirus 30 isolated in belém, brazil.echovirus (echo) 30 or human enterovirus b is the most frequent enterovirus associated with meningitis cases. epidemics and outbreaks of this disease caused by echo 30 have occurred in several countries. in brazil, echo 30 has been isolated from sporadic cases and outbreaks that occurred mainly in the south and southeast regions. we used rt-pcr to examine echo 30 isolates from meningitis cases detected from march 2002 to december 2003 in belém, state of pará, in northern brazil. the patients wer ...200717873993
[construction and sequencing of full-length cdna clone of swine vesicular disease virus strain hk'1/70].by race, 2 overlapping cdna fragments (3'pcr and 5'pcr fragments) covering the full genome of swine vesicular disease virus strain hk'1/70 were amplified from total rna extracted from experimentally infected suckling mice. these fragments were cloned into pgem-t easy vector, respectively. 5'pcr fragment was digested by enzymes of aat ii and bssh ii, and the aat ii-bssh ii-digested 5'pcr fragment was obtained and cloned into the recombinant pgem-t easy vector containing 3'pcr fragment,the recombi ...200717886721
tissue uptake of mercury is changed during the course of a common viral infection in mice.mercury (hg) has been shown to have immunotoxic effects and to influence the severity of infection. however, the impact of infection on the normal hg homeostasis in different target organs involved in the disease process has not been studied. in this study, hg was measured through inductively coupled plasma-mass spectrometry (icp-ms) in the intestine, serum, liver, and brain on days 3, 6, and 9 of coxsackievirus b3 (cvb3) infection in female balb/c mice. the severity of the infection was assesse ...200817888900
coxsackievirus b3 infection affects metal-binding/transporting proteins and trace elements in the pancreas in mice.the trigger of juvenile diabetes has been suggested to be an interaction between a virus and trace elements, where enteroviruses, including coxsackievirus b3 (cvb3), have been discussed as potential initiators. the aim of this study was to investigate the effects in the pancreas on gene expressions of metallothionein 1 (mt1), divalent metal transporter 1 (dmt1), and zinc transporter 5 (znt-5) and concomitant changes in iron (fe), copper (cu), and zinc (zn) in serum and pancreas of balb/c mice on ...200717895834
recombinant coxsackievirus vectors for prevention and therapy of virus-induced heart disease.cardiovascular diseases are the major cause of human death and have been linked to many different risk factors. among them, coxsackievirus b3 (cvb3), as a member of the enterovirus group, is one of the most important infectious agents of virus-induced myocarditis. despite the fact that the molecular structure of this pathogen has been characterized very precisely, there is no virus-specific preventive or therapeutic procedure against cvb3-induced heart disease in clinical use today. a promising ...200817897883
a one-step reverse transcriptase loop-mediated isothermal amplification assay for simple and rapid detection of swine vesicular disease virus.this report describes the development of a one-step reverse transcriptase loop-mediated isothermal amplification (rt-lamp) assay for the detection of swine vesicular disease virus (svdv). the assay detects the virus rapidly, within 30-60 min and the result is visualised either by gel-electrophoresis or by the naked eye through the addition of sybrgreen. a collection of 28 svdv isolates were tested positive, while heterologous viruses such as foot-and-mouth disease virus and vesicular stomatitis ...200817920701
using ifn-gamma as a biomarker for detecting exposure to viral pathogens.to determine whether interferon gamma (ifn-gamma) can be used as a biomarker of exposure to viral pathogens, 12-week-old balb/c mice were injected intraperitoneally with coxsackievirus b3 (cvb3) or coxsackievirus b4 (cvb4) diluted in sterilized phosphate-buffered saline (pbs). control mice were injected with pbs only. four months after viral infection, mouse spleen cells were harvested and assayed for the release of ifn-gamma by memory t cells after in vitro stimulation with viral antigens, phyt ...200817926092
endogenous low-level expression of the coxsackievirus and adenovirus receptor enables coxsackievirus b3 infection of rd cells.cells in which the appropriate viral receptor cannot be detected may paradoxically act as a host to the virus. for example, rd cells are often considered to be non-permissive for infection with coxsackievirus and adenovirus receptor (car)-dependent group b coxsackieviruses (cvb), insofar as inoculated cell monolayers show little or no cytopathic effect (cpe) and immunohistological assays for car have been consistently negative. supernatants recovered from rd cells exposed to cvb, however, contai ...200717947527
coxsackievirus b3 infection and pbde exposure causes organ-specific effects on cyp-gene expression in the mouse.common viral infections have been shown to change the tissue distribution of xenobiotics, including polybrominated diphenyl ethers (pbdes). in previous studies, it has been shown that cyp2b gene expression is induced after pbde exposure whereas coxsackievirus b3 (cbv3) infection suppresses the expression of cyp-gene expression in the liver. in the present study, cvb3 adapted to balb/c mice was used to study the combined effects of infection and exposure to pure bde-99 or the commercial mixture b ...200717964053
viral infection and pbde exposure interact on cyp gene expression and enzyme activities in the mouse liver.in the present study coxsackievirus b3 (cvb3) adapted to balb/c mice was used to examine whether infection affects xenobiotic-metabolising cyp1a1 and cyp2b gene expression (measured by rt-pcr) and the corresponding enzyme activities of ethoxyresorufin-o-deethylase (erod) and pentoxyresorufin-o-depentylase (prod), as observed on day 3 of infection. to study the simultaneous effects of xenobiotic exposure, mice were administered the polybrominated diphenyl ether (pbde) compounds bde-99 (single con ...200717964055
rapid and differential diagnosis of foot-and-mouth disease, swine vesicular disease, and vesicular stomatitis by a new multiplex rt-pcr assay.a highly sensitive and specific one-step multiplex rt-pcr assay has been developed and standardised for the simultaneous and differential detection of the most important vesicular viruses affecting livestock: foot-and-mouth disease virus (fmdv), swine vesicular disease virus (svdv), and vesicular stomatitis virus (vsv). the method uses three primer sets, each one specific for the corresponding virus, selected to detect of all serotypes of fmd and vs. the detection range was confirmed by examinat ...200817964668
[inhibitory effect of chinese herbal medicine xin-kang oral liquid on replication of cvb3 rna in coxsackievirus b3 infected mice].to investigate the cvb3 rna concentration in myocardial tissues and inhibitory effect of chinese herbal medicine xin-kang oral liquid on viral rna replication in coxsackievirus b3 infected myocardium.200717971932
prospective identification of enteroviruses involved in meningitis in 2006 through direct genotyping in cerebrospinal fluid.enterovirus infections were investigated with special emphasis on performing rapid molecular identification of enterovirus serotypes responsible for aseptic meningitis directly in cerebrospinal fluid (csf). enterovirus genotyping was carried out directly with specimens tested for the diagnostic procedure, using two seminested pcr assays designed to amplify the complete and partial gene sequences encoding the vp1 and vp4/vp2 capsid proteins, respectively. the method was used for identifying the e ...200817977989
tinnitus and coxsackie b infections: a case series.tinnitus is a frequent and often debilitating condition. there is consensus in the scientific community that there exist various forms of tinnitus, which differ in their pathogenesis. here we report a series of five cases where the onset of tinnitus was associated with viral infections. in all five patients elevated antibodies against coxsackie b have been detected. this observation suggests that coxsackie b virus infections might be involved in the development of some cases of tinnitus and indi ...200717984924
junctional gating: the achilles' heel of epithelial cells in pathogen infection.mucosal epithelial cells are a major barrier restricting pathogen entry and, paradoxically, an important entry port for respiratory and enteric viruses. elegant studies in this issue of cell host & microbe describe how coxsackievirus b3 (related to human poliovirus) infects polarized epithelial cells by engaging two transmembrane proteins of the tight junctions, occludin and car. a distinctive endocytic mechanism opens the junctions and gates infectious virus entry.200718005729
coxsackievirus entry across epithelial tight junctions requires occludin and the small gtpases rab34 and rab5.the major group b coxsackievirus (cvb) receptor is a component of the epithelial tight junction (tj), a protein complex that regulates the selective passage of ions and molecules across the epithelium. cvb enters polarized epithelial cells from the tj, causing a transient disruption of tj integrity. here we show that cvb does not induce major reorganization of the tj, but stimulates the specific internalization of occludin-a tj integral membrane component-within macropinosomes. although occludin ...200718005733
complete genome sequences for nine simian enteroviruses.analysis of the vp1 capsid-coding sequences of the simian picornaviruses has suggested that baboon enterovirus (baev), sv19, sv43 and sv46 belong to the species human enterovirus a (hev-a) and sa5 belongs to hev-b, whereas sv4/a2 plaque virus (two isolates of a single serotype), sv6 and n125/n203 (two isolates of a single serotype) appear to represent new species in the genus. we have further characterized by complete genomic sequencing the genetic relationships among the simian enteroviruses se ...200718024906
molecular analysis of the role of ires stem-loop v in replicative capacities and translation efficiencies of coxsackievirus b3 mutants.coxsackievirus b3 (cvb3) is a principal viral cause of acute myocarditis in humans and has been 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, it has been demonstrated elsewhere that, for several wild-type cb3 strains, the primary molecular determinant of cardiovirulence phenotype localizes to the 5' nontranslated region (5'ntr) and capsid. stable ...200918027104
interactions between multiple genetic determinants in the 5' utr and vp1 capsid control pathogenesis of chronic post-viral myopathy caused by coxsackievirus b1.mice infected with coxsackievirus b1 tucson (cvb1(t)) develop chronic, post-viral myopathy (pvm) with clinical manifestations of hind limb muscle weakness and myositis. the objective of the current study was to establish the genetic basis of myopathogenicity in cvb1(t). using a reverse genetics approach, full attenuation of pvm could only be achieved by simultaneously mutating four sites located at c706u in the 5' untranslated region (5' utr) and at y87f, v136a, and t276a in the vp1 capsid. engi ...200818029287
amiloride derivatives inhibit coxsackievirus b3 rna replication.amiloride derivatives are known blockers of the cellular na(+)/h(+) exchanger and the epithelial na(+) channel. more recent studies demonstrate that they also inhibit ion channels formed by a number of viral proteins. we previously reported that 5-(n-ethyl-n-isopropyl)amiloride (eipa) modestly inhibits intracellular replication and, to a larger extent, release of human rhinovirus 2 (hrv2) (e. v. gazina, d. n. harrison, m. jefferies, h. tan, d. williams, d. a. anderson and s. petrou, antiviral re ...200818032495
calpain 1 and 2 are required for rna replication of echovirus 1.calpains are calcium-dependent cysteine proteases that degrade cytoskeletal and cytoplasmic proteins. we have studied the role of calpains in the life cycle of human echovirus 1 (ev1). the calpain inhibitors, including calpeptin, calpain inhibitor 1, and calpain inhibitor 2 as well as calpain 1 and calpain 2 short interfering rnas, completely blocked ev1 infection in the host cells. the effect of the inhibitors was not specific for ev1, because they also inhibited infection by other picornavirus ...200818032503
production of cross-reactive peptide antibodies against viral capsid proteins of human enterovirus b to apply diagnostic reagent.the coxsackievirus group b (cvb) of the genus enterovirus and the species human enterovirus b is a nonenveloped virus containing a single-stranded positive-sense rna genome. coxsackievirus has icosahedral symmetry and four capsid proteins, vp1, vp2, vp3, and vp4. specific antibodies against each viral protein are prerequisites for various studies. in this study, we developed seven peptide-derived antibodies directed against coxsackievirus vp1 (no1-no5), vp2 (b3), and vp3 (gl3). we developed a ty ...200718037786
molecular biology and pathogenesis of viral myocarditis.myocarditis is a cardiac disease associated with inflammation and injury of the myocardium. several viruses have been associated with myocarditis in humans. however, coxsackievirus b3 is still considered the dominant etiological agent. the observed pathology in viral myocarditis is a result of cooperation or teamwork between viral processes and host immune responses at various stages of disease. both innate and adaptive immune responses are crucial determinants of the severity of myocardial dama ...200818039131
qihong prevents death in coxsackievirus b3 induced murine myocarditis through inhibition of virus attachment and penetration.viral myocarditis affects about 5% to 20% of the population. so far, there are not many effective antiviral treatments available. qihong, the combination of the extracts from astragali (huangqi), rhadiola rosea (hongjingtian), and sophora flavescens (kushen), was developed based on laboratory research. the aim of this study was to investigate the effect and mechanism of qihong on coxsackievirus b3 (cvb3)-induced myocarditis. the antiviral activity of qihong in vitro was evaluated on hela and ver ...200718040068
cloning and expression of coxsakievirus b3 viral protein-1 in e. coli.viral protein-1 (vp1) is a major capsid protein of coxsakievirus b3 (cvb3) that plays an important role in directing viruses towards permissive cells and acts as a main antigenic site of the virus in eliciting of host immune response, hence it seems vp1 can be considered as a vaccine candidate against cvb3 infection. in this study, cdna of vp1 was prepared, cloned into pet expression vector and the recombinant protein (vp1) was over expressed in e. coli.200718051774
amelioration of coxsackievirus b3-mediated myocarditis by inhibition of tissue inhibitors of matrix metalloproteinase-1.coxsackievirus b3 (cvb3) is a major cause of acute myocarditis, a serious condition that is refractory to treatment. myocardial damage results in tissue remodeling that, if too extensive, may contribute to disease. remodeling is achieved by extracellular proteolysis mediated by the matrix metalloproteinases (mmps), and mmp activity is counterbalanced by tissue inhibitors of mmps (timps). we show herein that timp-1 expression is induced in the myocardium by cvb3 infection. surprisingly, timp-1 kn ...200718055551
replication of coxsackievirus b3 in primary cell cultures generates novel viral genome deletions.coxsackievirus b3 (cvb3) generates 5'-terminally deleted genomes (tds) during replication in murine hearts. we show here that cvb3 populations with tds can also be generated within two to three passages of cvb3 in primary, but not immortalized, cell cultures. deletions of less than 49 nucleotides increase in size during passage, while 5' tds of 49 nucleotides appear to be the maximum deletion size. the cellular environment of contact-inhibited primary cell cultures or the myocardium in vivo is s ...200818057248
active coxsackieviral b infection is associated with disruption of dystrophin in endomyocardial tissue of patients who died suddenly of acute myocardial infarction.in this study, we evaluated the potential direct role of enterovirus (ev) cardiac infections in the pathogenesis of myocardial infarction (mi).200718061067
[c3d enhances immune response to the secreted form of coxsackie virus b3 vp1 dna vaccine].to explore a strategy to enhance the specific immune response induced by secreted form of coxsackie virus b3 (cvb3) capsid protein 1 (svp1) gene vaccination against coxsackie virus infection.200718067834
analysis of echovirus 30 isolates from russia and new independent states revealing frequent recombination and reemergence of ancient lineages.we studied two genome regions, vp1 and 3d, of 48 echovirus 30 (e30) isolates from russia and the new independent states. in vp1, most isolates were similar to european strains reported earlier, and frequent change of circulating subgroups was noticed. we also observed, in 2003-2006, the reemergence of a group of e30 strains with a vp1 region very distant from most modern e30 strains and remotely similar to e30 isolates from the 1960s and the 1970s. a study of the 3d genome region detected multip ...200818077646
dynamics of picornavirus rna replication within infected cells.replication of many picornaviruses is inhibited by low concentrations of guanidine. guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2c protein. using in vitro replication assays it has been determined previously that guanidine blocks the initiation of negative-strand synthesis. we have now examined the dynamics of rna replication, measured by quantitative rt-pcr, within cells infected with either swine vesicular disease virus (an enterovirus) o ...200818198379
detection of echovirus 18 in human breast milk.we detected enteroviral rna and cultured infectious virus from a series of banked breast milk samples from the mother of an infant with neonatal sepsis; sequencing of the enterovirus isolate identified it as echovirus type 18. in this case, it is possible that enterovirus transmission occurred through the breast milk.200818199781
primary neurons become less susceptible to coxsackievirus b5 following maturation: the correlation with the decreased level of car expression on cell surface.coxsackievirus b (cvb) is one of the major pathogens of aseptic meningitis and meningioencephalitis, particularly in newborn infants. to analyze the influence of neural maturation on susceptibility to cvb infection, we prepared immature and mature neurons from 16-day-old balb/c embryonic cortex. in contrast to immature neurons, mature neurons were less susceptible to cvb5 infection, as indicated by the decrease of cytopathic features. in mature neurons, progeny virus production was significantly ...200818205224
temporal changes in stem cells in the circulation and myocardium of mice with coxsackie virus b3-induced myocarditis.our goal was to investigate temporal changes in stem cell in the circulation and myocardium of mice with coxsackie virus b3-induced myocarditis. groups of mice were administered eagle's minimal essential medium or virus solution. the animals were further divided into six subgroups based on the following time points post-inoculation: 1, 3, 7, 14, 21, and 28 days. ten animals were studied in each subgroup. circulating blood mononuclear cells were collected from the heart and analyzed using flow cy ...200818206181
protective effects of carvedilol in murine model with the coxsackievirus b3-induced viral myocarditis.carvedilol, a nonselective beta-blocker with additional alpha1-adrenergic blocking and antioxidant properties, has been shown to be cardioprotective in experimental myocarditis. however, the antioxidative effects of carvedilol have not been investigated in the setting of acute viral myocarditis. therefore, this study investigated whether carvedilol protects against viral myocarditis primarily by its antioxidant and/or antiinflammatory properties. in a coxsackievirus b3 murine myocarditis model ( ...200818209574
do viruses cause inner ear disturbances?the association of viral infection to inner ear disease is controversial. experiments on animals show that several viruses are capable of causing hearing loss, if applied into the perilymph. some of these have specific affinity to the cellular type of the inner ear, as sensory epithelia and cochlear nerve. some viruses as adenoviruses and coxsackie virus b have specific car receptors that are identified in different cell types, whereas other act by attaching onto nonspecific cellular surface rec ...200818235204
detection of dual-infected cases of adenoviruses and coxsackieviruses type b by real-time pcr but not by the conventional viral culture technique.the aim of this study was to evaluate the applicability of diagnostic methods for dual-infected cases of human adenoviruses (advs) and coxsackieviruses type b (cbs). for this purpose, 100 nasopharyngeal samples from patients with acute exudative tonsillitis and clinically suspected adv infection were analyzed. using pcr and real-time pcr techniques for advs and cbs, we found 86 advs-only positive samples; we also found five dual-infected samples containing 5.4 x 10(5) to 7.1 x 10(8) copies/ml of ...200718257468
detection of viral bioagents using a shear horizontal surface acoustic wave biosensor.viruses are of high medical and biodefense concern and their detection at concentrations well below the threshold necessary to cause health hazards continues to be a challenge with respect to sensitivity, specificity, and selectivity. ideally, assays for accurate and real time detection of viral agents would not necessitate any pre-processing of the analyte, which would make them applicable for example to bodily fluids (blood, sputum) and man-made as well as naturally occurring bodies of water ( ...200818262781
mutation variants generated from nonvirulent coxsackievirus b3 acquire virulence phenotypes by active virus replication.to understand coxsackievirus b3 (cvb3) virulence at the molecular level.200818268408
subcellular distribution of swine vesicular disease virus proteins and alterations induced in infected cells: a comparative study with foot-and-mouth disease virus and vesicular stomatitis virus.the intracellular distribution of swine vesicular disease virus (svdv) proteins and the induced reorganization of endomembranes in ibrs-2 cells were analyzed. fluorescence to new svdv capsids appeared first upon infection, concentrated in perinuclear circular structures and colocalized to dsrna. as in foot-and-mouth disease virus (fmdv)-infected cells, a vesicular pattern was predominantly found in later stages of svdv capsid morphogenesis that colocalized with those of non-structural proteins 2 ...200818279902
reductions of e. coli, echovirus type 12 and bacteriophages in an intermittently operated household-scale slow sand filter.point-of-use (pou) drinking water treatment technology enables those without access to safe water sources to improve the quality of their water by treating it in the home. one of the most promising emerging pou technologies is the biosand filter (bsf), a household-scale, intermittently operated slow sand filter. over 500,000 people in developing countries currently use the filters to treat their drinking water. however, despite this successful implementation, there has been almost no systematic, ...200818281076
potent oncolytic activity of human enteroviruses against human prostate cancer.oncolytic virotherapy offers a unique treatment modality for prostate cancer, especially stages that are resistant to current therapies, with the additional benefit of preferentially targeting tumor cells amongst an environment of healthy tissue. herein, the low pathogenic enteroviruses; coxsackievirus a21 (cva21), as well as a bio-selected variant of coxsackievirus a21 (cva21-dafv) and echovirus 1 (ev1) are evaluated as novel oncolytic agents against human prostate cancer.200818288643
coxsackievirus b4 infection of murine foetal thymus organ cultures.the infection of foetal thymus with coxsackievirus b4 (cv-b4) e2 has been studied ex vivo by using cd-1 mice on foetal day 14, as a ready source of organs for experimentation to investigate the hypothesis of the role of thymic viral infections in the pathogenesis of type 1 diabetes. the replication of cv-b4 e2 in murine foetal thymus organ cultures has been demonstrated by evaluating the levels of positive- and negative-stranded viral rna in cells by using a real-time quantitative rt-pcr method ...200818297721
molecular typing and epidemiology of non-polio enteroviruses isolated from yunnan province, the people's republic of china.this report presents an overview of human enteroviruses in yunnan province, the people's republic of china. a total of 210 non-polioviruses isolated under acute flaccid paralysis (afp) surveillance during a total study period of 5 years--1997 to 2000 and 2004--were examined. of the 210 non-poliovirus isolates, 12 adenoviruses were serologically identified, and the remaining 198 isolates were used for molecular typing. the viral genomes of 195 non-polio enteroviruses (npevs) on vp1 partial region ...200818297723
enumeration and functional evaluation of virus-specific cd4+ and cd8+ t cells in lymphoid and peripheral sites of coxsackievirus b3 infection.previous studies have suggested that coxsackievirus b (cvb) activates cd8(+) t cells in vivo, but the extent of this activation and the antigen specificity of the cd8(+) t cells remain uncertain. furthermore, cvb-induced cd4(+) t-cell responses have not been carefully investigated. herein, we evaluate cd8(+) and cd4(+) t-cell responses both in a secondary lymphoid organ (spleen) and in peripheral tissues (heart and pancreas), using a recombinant cvb3 (rcvb3.6) that encodes well-characterized cd8 ...200818305030
[receptor specificity of human enteroviruses].the review presents the currently available data on the receptor specificity of enteroviruses. it discusses whether changes in the receptor specificity of enteroviruses may play a role in their in vitro and in vivo reproduction.200818318127
[molecular epidemiology of echo 6 virus, the causative agent of the 2006 outbreak of serous meningitis in khabarovsk].a total of 3194 cases of enterovirus meningitis were notified in the russian federation in 2005, of them there were 1434 cases in the khabarovsk territory. enteroviruses were isolated from 1020 out of the virologically studied 1362 patients from the khabarovsk territory. viruses e6 and e30 were isolated in 80 and 14.7% of cases, respectively. e1, e3, e7, e33, coxsackie virus b1, b4, b5, and a10 were sporadically detected. the e6 strains isolated in komsomolsk-on-amur were identical while e6 stra ...200818318129
[molecular-biological identification of pathogens which caused an outbreak of viral encephalitis in jinan area].to investigate the etiology of the outbreak of viral encephalitis in jinan area in 2003.200718322587
imatinib mesylate attenuates fibrosis in coxsackievirus b3-induced chronic myocarditis.coxsackievirus b3 (cvb3)-induced chronic myocarditis in mice is accompanied by severe fibrosis and by sustained elevation of platelet-derived growth factor (pdgf)-a, -b, and -c levels in the cardiac tissue. to test if pdgf stimulation of resident fibroblasts causally contributes to fibrosis, we employed inhibition of pdgf receptor signalling with the orally available kinase inhibitor imatinib.200818326555
ablation of matrix metalloproteinase-9 increases severity of viral myocarditis in mice.coxsackievirus b3 (cvb3) causes human myocarditis, which can result in cardiac damage, maladaptive remodeling, and heart failure. matrix metalloproteinases (mmp)-8 and -9 have been identified in virus-infected myocardium, but their particular roles and underlying mechanisms of effect are unknown. for the first time, we examine the severity of cvb3-induced myocarditis in mmp-8-and mmp-9-deficient mice.200818332263
the thiazolobenzimidazole tbze-029 inhibits enterovirus replication by targeting a short region immediately downstream from motif c in the nonstructural protein 2c.tbze-029 {1-(2,6-difluorophenyl)-6-trifluoromethyl-1h,3h-thiazolo[3,4-a]benzimidazole} is a novel selective inhibitor of the replication of several enteroviruses. we show that tbze-029 exerts its antiviral activity through inhibition of viral rna replication, without affecting polyprotein processing. to identify the viral target of tbze-029, drug-resistant coxsackievirus b3 (cvb3) was selected. genotyping of resistant clones led to the identification of three amino acid mutations in nonstructura ...200818337578
infection of primary cultures of murine splenic and thymic cells with coxsackievirus b4.infection of primary cultures of total splenic and thymic cells from balb/c and c3h/hen mice with cvb4 e2 and jvb strains has been investigated. the presence of positive-strand viral rna within cells was determined by semi-nested rt-pcr, and viral replication was attested by detection of intracellular negative-strand viral rna and by release of infectious particles in culture supernatants. viral replication occurred with both cvb4 strains to an extent dependent on the genetic background of the h ...200818352912
characterization of the protective capability of a recombinant coxsackievirus b3 variant expressing interferon-gamma.several different procedures have been developed to deliver essential genes to an organism by viral vectors. some reports have already been published demonstrating the potential to use enteroviruses as transfer vehicles. one application of these viral vectors is the organ-specific expression of immunoregulatory cytokines. it has been shown previously that local expression of interferon-gamma (ifn-gamma) by the recombinant coxsackievirus cvb3/ifn-gamma conferred protection against virus-caused di ...200818355121
coxsackie b viruses: an introduction. 200818357762
group b coxsackievirus virulence.that which is understood of virulence phenotypes in the picornaviruses derives in large part from studies of artificially attenuating phenotypes rather than through examination of naturally occurring virus strains. the cvb replicate well in a variety of different murine and human cell cultures, making them excellent viruses with which to engage the problem of how the host environment interacts with specific viral genetics to promote varying efficiencies of viral replication. it is not known how ...200818357765
the coxsackievirus and adenovirus receptor.the coxsackievirus and adenovirus receptor (car) has been studied extensively since its identification and isolation in 1997. the car is an immunoglobulin superfamily protein with two extracellular ig-like domains, a single membrane-spanning sequence, and a significant cytoplasmic domain. it is structurally and functionally similar to the junctional adhesion molecules. the amino terminal domain, distal from the membrane, has been structurally characterized alone, bound to the adenovirus fiber kn ...200818357766
coxsackievirus b rna replication: lessons from poliovirus.the replication of coxsackievirus rna occurs with rapid onset, starting approximately 2.5 h after infection. the mechanisms entailing the rna replication of enteroviruses, like coxsackievirus and poliovirus, are highly conserved. these processes require two steps of rna amplification: (i) complete synthesis of the negative-strand rna using input rna as the template and (ii) synthesis of the positive-strand rna using the intermediate negative-strand rna as the template. successful enterovirus rna ...200818357767
cvb translation: lessons from the polioviruses.our understanding of coxsackie b virus translation and replication has benefited greatly from half a century of research on the closely related polioviruses. like poliovirus, coxsackievirus gene expression is controlled largely at the translation level and coxsackievirus infection results in profound changes in the profile of mrnas with access to the protein synthesis machinery of the host cell. this review chronicles the advances in understanding translational control by the enteroviruses, prim ...200818357768
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