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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 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
[relationship between eb virus, cytomegalo virus, herpes simplex virus and coxsackievirus infection and relapse of multiple sclerosis].to study the relation between the recent active infection with epstein-barr virus, cytomegalovirus,herpes simplex virus-1, coxsackievirus b i-iv and the relapse of relapsing-remitting multiple sclerosis (rr ms).200819544649
molecular epidemiological study of hev-b enteroviruses involved in the increase in meningitis cases occurred in spain during 2006.human enteroviruses are one of the main etiological agents of aseptic meningitis and other central nervous system infections, particularly the serotypes included in the enterovirus b species. molecular methods have proved useful to identify serotypes in clinical samples, facilitating the epidemiological study of these viruses. in the spring of 2006, there was a significant increase in meningitis cases caused by enteroviruses in spain. in the present study, 138 enteroviruses directly detected in ...200818428125
development of robust antiviral assays for profiling compounds against a panel of positive-strand rna viruses using atp/luminescence readout.the development of antiviral assays using an atp/luminescence-based readout to profile antiviral compounds against the positive-strand rna viruses: yellow fever virus (yfv), west nile virus (wnv), sindbis virus, and coxsackie b virus, representing three virus families, is described. this assay readout is based upon the bioluminescent measurement of atp in metabolically active cells. antiviral efficacy was determined by measuring the atp level in cells that were protected from the viral cytopathi ...200818433887
a raft-derived, pak1-regulated entry participates in alpha2beta1 integrin-dependent sorting to caveosomes.we have previously shown that a human picornavirus echovirus 1 (ev1) is transported to caveosomes during 2 h together with its receptor alpha2beta1 integrin. here, we show that the majority of early uptake does not occur through caveolae. alpha2beta1 integrin, clustered by antibodies or by ev1 binding, is initially internalized from lipid rafts into tubulovesicular structures. these vesicles accumulate fluid-phase markers but do not initially colocalize with caveolin-1 or internalized simian vir ...200818448666
remission of cvb3-induced viral myocarditis by in vivo th2 polarization via hydrodynamics-based interleukin-4 gene transfer.regulation of th polarization was critical for the prevention of coxsackievirus b3 (cvb3) induced myocarditis. in the present study, interleukin (il)-4 was over-expressed by hydrodynamics-based gene transfection (hgt) to induce the in vivo th2 bias and evaluate the influence of th polarization on the pathogenesis of cvb3-myocaditis.200818512734
a laboratory study of survival of selected microorganisms after heat treatment of biowaste used in biogas plants.the aim of the study was to assess the effect of pasteurisation, as set by the european regulation ec 1774/2002, on selected pathogens and indicator organisms. unpasteurised substrate (biowaste), including animal by-products from a full-scale biogas plant was heat treated under laboratory conditions at 70 degrees c and 55 degrees c for 30 min and 60 min. heat treatment at 55 degrees c for 60 min was not sufficient to achieve a hygienically acceptable product. heat treatment at 70 degrees c for 3 ...200818513960
proteasome inhibition attenuates coxsackievirus-induced myocardial damage in mice.coxsackievirus b3 (cvb3) is one of the most prevalent pathogens of viral myocarditis, which may persist chronically and progress to dilated cardiomyopathy. we previously demonstrated a critical role of the ubiquitin-proteasome system (ups) in the regulation of coxsackievirus replication in mouse cardiomyocytes. in the present study, we extend our interest to an in vivo animal model to examine the regulation and role of the ups in cvb3-induced murine myocarditis. male myocarditis-susceptible a/j ...200818515649
the structure and function of a cis-acting element located upstream of the ires that influences coxsackievirus b3 rna translation.we have investigated the importance of a conserved hexa-nucleotide stretch in the apical loop within stem-loop c (sl c, nt 104-180), upstream of the ribosome landing site, on cvb3 ires function. the deletion or substitution mutation at this apical loop resulted in significant decrease in ires activity. both the mutant ires rnas failed to interact with certain trans-acting factors. furthermore, expression of cvb3 2a protease significantly enhanced ires activity of the wild type, but the effect wa ...200818533219
fatal neonatal myocarditis caused by a recombinant human enterovirus-b variant.we report a case of fatal myocarditis in a newborn infant who was infected with a human enterovirus detected by throat culture and rt-pcr for viral rna in plasma. whole genome sequence analysis revealed the virus to be a genomic chimera that likely arose from recombination between coxsackievirus b3 and two recently identified enteroviruses, ev 86 and ev97.200818536618
cardiac-targeted rna interference mediated by an aav9 vector improves cardiac function in coxsackievirus b3 cardiomyopathy.rna interference (rnai) has potential to be a novel therapeutic strategy in diverse areas of medicine. in this paper, we report on targeted rnai for the treatment of a viral cardiomyopathy, which is a major cause of sudden cardiac death or terminal heart failure in children and young adults. rnai therapy employs small regulatory rnas to achieve its effect, but in vivo use of synthetic small interfering rnas is limited by instability in plasma and low transfer into target cells. we instead evalua ...200818548221
comparison of automated nucleic acid extraction methods with manual extraction.automated nucleic acid extractors can improve workflow and decrease variability in the clinical laboratory. we evaluated qiagen ez1 (valencia, ca) and biomérieux (durham, nc) easymag extractors compared with qiagen manual extraction using targets and matrices commonly available in the clinical laboratory. pooled samples were spiked with various organisms, serially diluted, and extracted in duplicate. the organisms/matrices were bordetella pertussis/bronchoalveolar lavage, herpes simplex virus ii ...200818556770
cleavage of eukaryotic initiation factor eif5b by enterovirus 3c proteases.the enteroviruses poliovirus (pv), coxsackie b virus (cvb) and rhinovirus (hrv) are members of picornaviridae that inhibit host cell translation early in infection. enterovirus translation soon predominates in infected cells, but eventually also shuts off. this complex pattern of modulation of translation suggests regulation by a multifactorial mechanism. we report here that eif5b is proteolytically cleaved during pv and cvb infection of cultured cells, beginning at 3 hours post-infection and in ...200818572216
coxsackievirus b3-induced myocarditis: infection of females during the estrus phase of the ovarian cycle leads to activation of t regulatory cells.transgenic female mice expressing the tnfalpha gene under the cardiac myosin promoter (tnf1.6) develop substantially increased myocarditis and increased numbers of cd4+th1 (interferon gamma+) cells when infected with coxsackievirus b3 (cvb3) during the diestrus and proestrus phases of the estrus cycle compared to females infected during the estrus and metestrus phases. cardiac virus titers were increased in females infected in estrus compared to females infected during the other phases. t regula ...200818586295
[matrine's inhibitory effect on apoptosis of cardiomyocytes induced by coxsackie virus b(3) and on calcium overload]. 200819099839
[intracellular clearance of coxsakievirus b3 infection by short interfering rna and its mechanism study].to evaluate the possibility of short interfering rna (sirna) inhibiting coxsackievirus b3 (cvb3) infection in vitro, and discover the mechanism initially.200819105337
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
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
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
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
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
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
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
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
expression of short hairpin rnas against the coxsackievirus b3 exerts potential antiviral effects in cos-7 cells and in mice.chemically synthesized small interfering rna (sirna) has been used as an anti-coxsackievirus b3 (cvb3) agent. herein, we investigated whether vector-derived short hairpin rnas (shrna) targeting cvb3 can exert antiviral activities, prior to their further application to viral vector system for efficient in vivo administration. employing transient transfection assays to in vivo mouse models as well as to in vitro cos-7 cell cultures, we directly demonstrated the potential antiviral activity of shrn ...200717222937
dysregulation of the ubiquitin-proteasome system by curcumin suppresses coxsackievirus b3 replication.curcumin (diferuloylmethane), a natural polyphenolic compound extracted from the spice turmeric, has been reported to have anti-inflammatory, antioxidant, and antiproliferative properties by modulating multiple cellular machineries. it inhibits several intracellular signaling pathways, including the mitogen-activated protein kinases (mapks), casein kinase ii (ckii), and the cop9 signalosome (csn), in various cell types. it has also been recently demonstrated that exposure to curcumin leads to th ...200717229707
antiviral treatment of coxsackie b virus infection in human pancreatic islets.enterovirus infections of the pancreatic islets are believed to trigger or precipitate the near total destruction of beta-cells that constitutes type 1 diabetes (t1d). this study investigated the ability of an anti-picornaviral compound, pleconaril, to block the replication of two beta-cell tropic coxsackie b4 virus (cbv-4) strains in isolated human islets. the two strains, vd2921 and v89 4557, with demonstrated abilities to cause non-lytic persistence or lytic infection, respectively, in islets ...200717239967
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
mda-5 is cleaved in poliovirus-infected cells.infections with rna viruses are sensed by the innate immune system through membrane-bound toll-like receptors or the cytoplasmic rna helicases rig-i and mda-5. it is believed that mda-5 is crucial for sensing infections by picornaviruses, but there have been no studies on the role of this protein during infection with poliovirus, the prototypic picornavirus. beginning at 4 h postinfection, mda-5 protein is degraded in poliovirus-infected cells. levels of mda-5 declined beginning at 6 h after inf ...200717267501
echovirus infection causes rapid loss-of-function and cell death in human dendritic cells.coxsackie b viruses (cvb) and echoviruses (ev) form a single species; human enterovirus b (hev-b), within the genus enterovirus. although hev-b infections are usually mild or asymptomatic, they can cause serious acute illnesses. in addition, hev-b infections have been associated with chronic immune disorders, such as type 1 diabetes mellitus and chronic myocarditis/dilated cardiomyopathy. it has therefore been suggested that these viruses may trigger an autoimmune process. here, we demonstrate t ...200717298395
new enteroviruses, ev-93 and ev-94, associated with acute flaccid paralysis in the democratic republic of the congo.surveillance of acute flaccid paralysis often identifies enteroviruses not typeable by virus neutralization in cell culture. during 2000 and 2001, 186 isolates from 138 children with acute flaccid paralysis in the democratic republic of the congo were sent for typing to the national reference centre for enteroviruses in lyon, france. the 5' utr of the viral genome could be amplified by pcr for 158 isolates from 114 patients. isolates from 89 patients were neutralizable, and contained non-polio e ...200717311342
partial 3d gene sequences of coxsackie viruses reveal interspecies exchanges.the 3d region of 46 clinical coxsackievirus strains, primarily belonging to the human enterovirus b species (hev-b), were analyzed using nucleotide distance matrices and phylogeny software. the conclusions from previously analyzed genomic regions (vp1-2a-2b-2c) of the aforementioned strains revealed that enteroviruses' inheritance is being guided by gene adaptation among viruses of different serotypes. in this report the comparison of partial vp1 and 3d gene phylogenies presented an obvious inco ...200717318426
protective immune responses in guinea pigs and swine induced by a suicidal dna vaccine of the capsid gene of swine vesicular disease virus.a suicidal dna vaccine based on a semliki forest virus (sfv) replicon was evaluated for the development of a vaccine against swine vesicular disease virus (svdv). the 1bcd gene of svdv was cloned and inserted into psca1, an sfv dna-based replicon vector. the resultant plasmid, psca/1bcd, was transfected into bhk-21 cells and the antigenicity of the expressed protein was confirmed using an indirect immunofluorescence assay. immunogenicity was studied in guinea pigs and swine. animals were injecte ...200717325356
enterovirus 94, a proposed new serotype in human enterovirus species d.the genus enterovirus (family picornaviridae) contains five species with strains isolated from humans: human enterovirus a (hev-a), hev-b, hev-c, hev-d and poliovirus. in this study, a proposed new serotype of hev-d was characterized. four virus strains were isolated from sewage in egypt and one strain from acute flaccid paralysis cases in the democratic republic of the congo. the complete genome of one environmental isolate, the complete coding sequence of one clinical isolate and complete vp1 ...200717325357
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
influence of neopterin and 7,8-dihydroneopterin on the replication of coxsackie type b5 and influenza a viruses.pteridine derivatives neopterin and 7,8-dihydroneopterin are produced by human macrophages and dendritic cells upon stimulation with interferon-gamma (ifn-gamma) and therefore become detectable in increased amounts in humans during cell-mediated (th1-type) immune response. compounds produced upon influence of cytokine ifn-gamma often exert antiproliferative and antiviral activity. the aim of this study was to investigate the effect of neopterin and 7,8-dihydroneopterin on the replication of coxs ...200716868770
in vitro (1)h nmr studies of rd human cell infection with echovirus 11.the effects of echovirus 11 infection on rd human cell line (derived from rhabdomyosarcoma) were studied using (1)h nmr spectroscopy and optical microscopy. both uninfected and infected cells consumed glucose and produced lactate, acetate and formate as extracellular metabolites. in infected whole cells, phosphocholine and uridine-sugar were observed in addition to the metabolites observed in uninfected cells. water-soluble intracellular metabolites of infected cells showed glutamine, phosphocho ...200717013981
bupleurum kaoi inhibits coxsackie b virus type 1 infection of ccfs-1 cells by induction of type i interferons expression.coxsackie b virus type 1 (cvb1) infection is known to cause high morbidity and mortality in children, however, there is no effective drug for treating this disease. the present study aimed to examine the antiviral activity of bupleurum kaoi (bk), a popular herbal drug for treating viral and bacterial infections, against cvb1 infection and its mechanisms of action. our data showed that bk neutralized the cvb1-induced cytopathic effect in human neonatal foreskin fibroblast cell line (ccfs-1/kmc), ...200717052829
2'-c-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus.we report on the potent and selective in vitro antiviral activity of 2'-c-methylcytidine (2'-c-metcyt) against foot-and-mouth disease virus (fmdv). fmdv belongs to the picornaviridae and has the potential to cause devastating epidemics in livestock. the 50% and 90% effective concentrations (ec50 and ec90) for inhibition of the fmdv-induced cytopathic effect (cpe) formation were 6.4+/-3.8 and 10.8+/-5.4 microm. comparable ec50 values for inhibition of viral rna synthesis were observed. treatment ...200717055073
strand-specific silencing of a picornavirus by rna interference: evidence for the superiority of plus-strand specific sirnas.rna interference triggered by small interfering rnas (sirnas) can be used to effectively contain viral spread. here, we report on the mechanism of action of sirnas targeting the medically important coxsackievirus b3 (cvb-3) as a typical representative of viruses with a non-segmented rna genome in positive-strand orientation. antiviral sirnas can be designed to target the genomic (+)-strand, the (-)-strand that occurs as a replication intermediate, or both. in the present study, two complementary ...200717112603
coxsackievirus-induced myocarditis in mice: a model of autoimmune disease for studying immunotoxicity.excellent animal models are available for virus-induced and autoimmune heart disease that are remarkably similar to human disease. developing good animal models for heart disease is crucial because cardiovascular disease is now the leading cause of death in the united states and is estimated to be the leading cause of death in the world by the year 2020. a significant proportion of heart disease in western populations is associated with inflammation. myocarditis, or inflammation of the heart mus ...200717161308
emergence of recent echovirus 30 lineages is marked by serial genetic recombination events.in an earlier report, different variants of echovirus 30 (e-30), an enterovirus serotype, were identified during two outbreaks in 1997 and 2000. here, the diversity of e-30 was investigated over a longer period (1991-2005) and the variations in four genomic segments were determined in 52 isolates involved in meningitis cases, to characterize the evolutionary processes underlying the emergence of lineages. phylogenetic analysis of the vp1 sequences showed that five phylogenetic variants succeeded ...200717170449
antiviral effects of pan-caspase inhibitors on the replication of coxsackievirus b3.the induction of apoptosis during coxsackievirus b3 (cvb3) infection is well documented. in order to study whether the inhibition of apoptosis has an impact on cvb3 replication, the pan-caspase inhibitor z-vad-fmk was used. the decreased cvb3 replication is based on reduced accumulation of both viral rna and viral proteins. these effects are due to an inhibitory influence of z-vad-fmk on the proteolytic activity of the cvb3 proteases 2a and 3c, which was demonstrated by using the target protein ...200717211569
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
[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
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
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
[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
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
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