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human cardiac inflammatory responses triggered by coxsackie b viruses are mainly toll-like receptor (tlr) 8-dependent.the group b coxsackieviruses are single-stranded rna viruses that have been implicated in viral myocarditis. viral infection of the myocardium, as well as the associated inflammatory response are important determinants of the virus-associated myocardial damage. although these viruses are known as cytopathic viruses that cause death of the host cell, their viral rna has been shown to persist in cardiac muscle contributing to a chronic inflammatory cardiomyopathy. thus, it is essential that we und ...200516008579
autoimmunity and coxsackievirus infection in primary sjogren's syndrome.exocrine gland epithelial cells are the target of autoimmune pathology in primary sjögren's syndrome (pss). their activated phenotype has incited the notion that they are infected by a virus. we recently presented evidence that coxsackieviruses may persistently infect the salivary glands of pss patients. we hypothesize that coxsackieviruses may play a permissive role for the perpetuation and possibly the induction of autoimmune disease in pss.200516014556
[effect of qihong capsule in inhibiting cell apoptosis induced by coxsackie virus b].to investigate whether the cell apoptosis could be induced by coxsackie virus b (cox b) and qihong capsule (qhc) has the inhibition on the cell apoptosis.200516025965
[experimental therapy of coxsackie b3 virus infection with immunomodulator contained in water-soluble penthaphylloides fruticosa extract].the possibility of using water-soluble substance extracted from p. fruticosa in experimental coxsackie b3 virus infection in newborn mice was studied. the curative action of the extract was studied by its injection to the infected animals for 7 days and its prophylactic action--by introducing it 24 hours and, repeatedly, 1 hour before infection. the study revealed the increase of such characteristics as survival rate, mean survival time, body weight dynamics, as well as decreased level of virus ...200516028531
[role of viral infections in the pathogenesis of type 1 diabetes].the precise role of viral infections in the pathogenesis of type 1 diabetes is still the subject of an important discussion. coxsackievirus b4 (cvb4) is the virus the most implicated by a series of epidemiological studies. pathogenic mechanisms underlying such a relationship implicate a molecular mimicry between cvb4 sequences and beta-cell autoantigens, but mainly a persistent cvb4 infection of pancreatic beta cells followed by a release of sequestered beta antigens and a "bystander" activation ...200516035284
interferon-gamma-induced activation of nitric oxide-mediated antiviral activity of macrophages caused by a recombinant coxsackievirus b3.cardiovascular disease is one of the major causes of human death and has been linked to many different risks including viral infections. coxsackievirus b3 (cvb3) is one of the most important pathogens responsible for virus-induced myocarditis. cytokines are normally involved in the control of cvb3 replication and pathogenesis. among them, interferon-gamma (ifn-gamma) in particular is highly protective against cvb3. a novel strategy to circumvent virus-caused heart disease is based on the develop ...200516035947
the role of erk1/2 activation in the infection of hela cells with human coxsackievirus b3.human coxsackievirus b3 (cvb3) is known to trigger in host cells a biphasic activation of extracellular signal-regulated kinase (erk1/2); i.e., early transient and late sustained activation. in this study, we explored (i) the role of erk1/2 activation in virus entry into cells and virus replication and (ii) cellular genes influenced by this activation in cvb3-infected hela cells. pretreatment of the cells with an erk1/2 inhibitor, pd98059 showed that early transient erk1/2 activation is not be r ...200516047735
a whole cell immunization-derived monoclonal antibody that protects cells from coxsackievirus a9 infection binds to both cell surface and virions.coxsackievirus a9 (cav-9) infects human rhabdomyosarcoma (rd) cells using an unidentified rgd-independent receptor. monoclonal antibodies were prepared by immunizing mice with intact rd cells and by selecting cells from the cytopathic effect of cav-9 for protection. here we describe a monoclonal antibody that binds to host cell plasma membrane and protects cells from virus infection. in addition, binding of the virus to cell monolayers was more efficient in the presence of the antibody, suggesti ...200516055201
a short pna targeting coxsackievirus b3 5'-nontranslated region prevents virus-induced cytolysis.targeting regulatory rna regions to interfere with the biosynthesis of a protein is an intriguing alternative to targeting a protein itself. regulatory regions are often unique in sequence and/or structure and, thus, ideally suited for specific recognition with a low risk of undesired side effects. targeting regulatory rna elements, however, is complicated by their complex three-dimensional structure, which poses kinetic and thermodynamic constraints to the recognition by a complementary oligonu ...200616121332
secrets of caveolae- and lipid raft-mediated endocytosis revealed by mammalian viruses.in recent years, it has been unambiguously shown that caveolae and lipid rafts can internalize cargo upon stimulation by multivalent ligands, demonstrated by the infectious entry routes of certain non-enveloped viruses that bind integrins or glycosphingolipids. we currently understand little about the membrane trafficking principles of this endocytic route, but it is clear that we cannot use paradigms from classical membrane traffic. recent evidence indicates that caveolae- and lipid raft-mediat ...200516126288
inhibition of coxsackie b virus infection by soluble forms of its receptors: binding affinities, altered particle formation, and competition with cellular receptors.we previously reported that soluble decay-accelerating factor (daf) and coxsackievirus-adenovirus receptor (car) blocked coxsackievirus b3 (cvb3) myocarditis in mice, but only soluble car blocked cvb3-mediated pancreatitis. here, we report that the in vitro mechanisms of viral inhibition by these soluble receptors also differ. soluble daf inhibited virus infection through the formation of reversible complexes with cvb3, while binding of soluble car to cvb induced the formation of altered (a) par ...200516140777
susceptibility of coxsackievirus b3 laboratory strains and clinical isolates to the capsid function inhibitor pleconaril: antiviral studies with virus chimeras demonstrate the crucial role of amino acid 1092 in treatment.at present, most promising compounds to treat enterovirus-induced diseases are broad-spectrum capsid function inhibitors which bind into a hydrophobic pocket in viral capsid protein 1 (vp1). coxsackievirus b3 (cvb3) nancy was the only prototypic enterovirus strain shown to be pleconaril-resistant. this study was designed to better understand the polymorphism of the hydrophobic pocket in cvb3 laboratory strains and clinical isolates and its implications for treatment with the capsid function inhi ...200516150864
developing an effective rna interference strategy against a plus-strand rna virus: silencing of coxsackievirus b3 and its cognate coxsackievirus-adenovirus receptor.coxsackievirus b3 (cvb-3) is a plus-strand rna virus that is believed to be the most common causal agent of viral myocarditis. since no specific treatment for cvb-3 infections is available to date, we and others have recently started to develop rna interference (rnai) approaches to prevent virus propagation. here we describe our strategy for the development of efficient small interfering rnas (sirnas) against viral genomes. initially, fusion constructs of a reporter (green fluorescent protein) a ...200516164410
specific interactions of mouse organ proteins with the 5'untranslated region of coxsackievirus b3: potential determinants of viral tissue tropism.coxsackievirus b3 (cvb3) infects multiple organs of humans and causes different diseases such as myocarditis, pancreatitis, and meningitis. however, the mechanisms of organ-specific tropism are poorly understood. coxsackievirus and adenovirus receptor (car) have been known to be important determinants for tissue tropism. however, current data on car mrna expression in certain organs of mouse did not correlate well with the susceptibility of the respective tissues, suggesting that intracellular p ...200516173012
classification and structure of echovirus 5'-utr sequences.enteroviruses are classified into two genetic clusters on the basis of 5'-utr and all echoviruses (ecv) are classified together with coxsackie b viruses (cbv), coxsackie a viruses (cav) types 2-10, 12, 14 and 16, and enteroviruses (ev) 68, 69, 71 and 73. during the present study, 5'-utr-derived sequences constituting the largest part of the internal ribosome entry site (ires) of ecvs were studied with respect to their possible secondary structures, which were predicted following the phenomenon o ...200516175335
sequence analysis of the 5' untranslated region of swine vesicular disease virus reveals block deletions between the end of the internal ribosomal entry site and the initiation codon.swine vesicular disease virus (svdv) is a picornavirus closely related to the human pathogen coxsackievirus b5. in common with other picornaviruses, the 5' untranslated region (5' utr) of svdv contains an internal ribosomal entry site (ires) that plays an important role in cap-independent translation. the aim of this study was to use rt-pcr and sequencing to characterize a fragment of the 5' utr encompassing the entire ires. sequence analysis demonstrated high nucleotide identities within the ir ...200516186229
[cytoplasmic expression of vp1 gene of coxsackievirus b3].to increase the immune effect of gene vaccine, t7 rna polymerase was used to establish a system of cytoplasmic expression.200516201472
[effect of chinese herbal medicine xin-kang oral liquid on interferon-induction and its antiviral activity in coxsackievirus b3 infected mice].to investigate the effect of chinese herbal medicine xin-kang oral liquid on interferon (ifn)-induction and its antiviral activity in coxsackievirus b3 virus strain (cvb3) infected mice.200516201482
viral entry, lipid rafts and caveosomes.lipid rafts and caveolae are detergent-insoluble plasma membrane microdomains, involved in cellular endocytic processes and signalling. several viruses, including a human pathogen, echovirus 1, and an extensively studied simian virus 40 utilize these domains for internalization into the host cells. interaction of viruses with receptors on the cell surface triggers specific conformational changes of the virus particle and can give rise to signalling events, which determine the mechanisms of virus ...200516203612
variability of virus attachment patterns to butterhead lettuce.enteric viruses account for most foodborne illness in the united states. the objective of this study was to determine whether the isoelectric point (pi) of viruses such as feline calicivirus (fcv), echovirus 11, and bacteriophages phix174 and ms2 had any effect on their attachment to butterhead lettuce. the adsorption of virus particles to the lettuce was variable. bacteriophage ms2 was the only virus that fit the current derjaguin-landau-verway-overbeek model of virus attachment. echovirus 11 h ...200516245715
stress-activated protein kinases are involved in coxsackievirus b3 viral progeny release.stress-activated protein kinases (sapks), consisting of c-jun n-terminal kinase (jnk) and p38 mitogen-activated protein kinase (p38 mapk), are activated upon various environmental stimuli, including viral infections. cellular survival and death signaling events following coxsackievirus b3 (cvb3) infection have been studied in relationship to viral replication, but the role of sapks has not been scrutinized. in this study, we found that the phosphorylation of jnk1/2 and p38 mapk was increased dur ...200516254323
structural and functional insights into the interaction of echoviruses and decay-accelerating factor.many enteroviruses bind to the complement control protein decay-accelerating factor (daf) to facilitate cell entry. we present here a structure for echovirus (ev) type 12 bound to daf using cryo-negative stain transmission electron microscopy and three-dimensional image reconstruction to 16-a resolution, which we interpreted using the atomic structures of ev11 and daf. daf binds to a hypervariable region of the capsid close to the 2-fold symmetry axes in an interaction that involves mostly the s ...200616272562
investigation into a school enterovirus outbreak using pcr detection and serotype identification based on the 5' non-coding region.a summer camp was followed by an outbreak of illness involving around 90 children. investigations included individual questionnaires, inspection of the camp facilities, and laboratory analysis of water and clinical samples. contamination of drinking and swimming water was demonstrated. an enterovirus was detected by polymerase chain reaction (pcr) and/or culture in 4/4 cerebrospinal fluid samples, 9/15 (60%) stool samples from symptomatic children and 2/9 (22%) stool samples from asymptomatic ch ...200516274511
[expression of antigenic region of vp1 gene of swine vesicular disease in escherichia coli].the antigenic region of vp1 gene of swine vesicular disease virus was amplified by reverse transcription polymerase chain reaction (rt-pcr) and nested polymerase chain reaction (npcr). after the amplified fragment was cloned into the expression vector pproex-htb. the insert position,the size and the reading frame of the insertion were identified by pcr, restriction digestion and sequence analysis of the recombinant plasmids. sds-page and western blot indicated that the transformed bl21(de3) by t ...200316279200
coxsackie b virus infection of mice: inoculation by the oral route protects the pancreas from damage, but not from infection.the pathogenesis of coxsackie b virus (cvb) infections is generally studied in mice by intraperitoneal (i.p.) injection, whereas the gastrointestinal tract is the natural porte d'entrée in humans. the present study was undertaken to compare systematically the influence of infection route on morbidity and pathology. swiss albino mice were infected with cvb3 (nancy) at different doses (5 x 10(3), 5 x 10(5), 5 x 10(7), 5 x 10(9) tcid50), given either i.p. or orally. virus could be isolated from sev ...200516298972
recombination in circulating human enterovirus b: independent evolution of structural and non-structural genome regions.the complete nucleotide sequences of eight human enterovirus b (hev-b) strains were determined, representing five serotypes, e6, e7, e11, cvb3 and cvb5, which were isolated in the former soviet union between 1998 and 2002. all strains were mosaic recombinants and only the vp2-vp3-vp1 genome region was similar to that of the corresponding prototype hev-b strains. in seven of the eight strains studied, the 2c-3d genome region was most similar to the prototype e30, ev74 and ev75 strains, whilst the ...200516298973
antiviral effects of sophoridine against coxsackievirus b3 and its pharmacokinetics in rats.coxsackievirus b3 (cvb3) is a major pathogen for acute and chronic viral myocarditis. the aim of this study was to investigate the antiviral effects of sophoridine, an alkaloid extracted from chinese medicinal herb, sophora flavescens, against cvb3, and the underlying pharmacokinetics. first, we determined the antiviral effects of sophoridine against cvb3 in in vitro (primarily cultured myocardial cells), in vivo (balb/c mice) and serum pharmacological experiments. then, we determined the pharma ...200616309710
application of a virological tracer method for the assessment of pathogen removal by physicochemical treatment and chemical disinfection.coxsackie b3 (coxb3) virus was used as a virological tracer for an assessment of the efficiency of pathogen removal by several typical physicochemical treatment and chemical disinfection processes, such as coagulation-filtration, ultra-filtration, and disinfection using chlorine and ozone, with regard to the pathogenic quality of the treated domestic wastewater for reuse purposes. the coxb3 virus was seeded to sterilized secondary effluent to make a raw water of known pathogenic level. after app ...200516312969
visualization and detection of infectious coxsackievirus replication using a combined cell culture-molecular beacon assay.rapid detection of infectious viruses is of central importance for public health risk assessment. by directly visualizing newly synthesized viral rna with molecular beacons (mbs), we have developed a generalized method for the rapid and sensitive detection of infectious viruses from cell culture. an mb, cvb1, specifically targeting the 5' noncoding region of the enterovirus genome was designed and synthesized. introduction of mb cvb1 into permeabilized cells highly infected with coxsackievirus b ...200516332827
effect of the angiotensin ii receptor blocker olmesartan on the development of murine acute myocarditis caused by coxsackievirus b3.ang ii (angiotensin ii) has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. the effects of arbs (ang ii receptor blockers) in the treatment of hypertension, congestive heart failure and myocardial fibrosis have been analysed extensively in human trials, as well as animal models, and the focus of interest is now directed to its pleiotropic effects, especially on inflammatory disorders. to investigate the effects of a new arb, olmes ...200616336207
t cells expressing the vgamma1 t-cell receptor enhance virus-neutralizing antibody response during coxsackievirus b3 infection of balb/c mice: differences in male and female mice.coxsackievirus b3 infection causes severe cardiac inflammation in male but not female mice. cd3+ t cells and t cells expressing the vgamma4 t cell receptor (tcr) predominate in the cardiac inflammatory cell infiltrate in infected male balb/c mice. infected females have mostly cd19+ (b lymphocyte) and vgamma1+ cells. no significant differences in cd11b+ (monocyte) cells were observed between the sexes. infected males showed a predominant cd4+th1 (ifngamma+) response, whereas females showed a pred ...200516359239
liposome-mediated transient transfection reduces cholesterol-dependent coxsackievirus infectivity.liposome-mediated gene delivery provides a powerful strategy for the study of gene function and for gene therapy. coxsackievirus b3 is an important human pathogen associated with various diseases. here we reported that liposome-mediated transient transfection of plasmid cdna inhibited coxsackieviral replication at the levels of rna, protein and viral progeny release. these inhibitory effects were observed in various cell types and by using different liposome reagents. we further showed that the ...200616375979
clinical and diagnostic findings of an echovirus meningitis outbreak in the north west of england.an outbreak of echovirus meningitis occurred in the north west of england in 2001. this paper reviewed the clinical features and the role of different diagnostic methods.200616397083
[the mechanisms responsible for the therapeutic effects of anti-fas ligand antibody on viral myocarditis in mice].viral myocarditis (vm) is one of the most common acquired myocardial diseases in children. however, its pathogenesis is not clear. recent studies indicate that the cytotoxicity mediated by cytotoxic t lymphocyte (ctl) plays an important role in the development of myocardial injury involved in vm. apoptosis mediated by fas/fasl pathway is an essential mechanism of target cells damage by ctl. in this study, the authors investigated the regulatory effects of neutralizing anti-fas ligand (anti-fasl) ...200516412356
virus-induced abl and fyn kinase signals permit coxsackievirus entry through epithelial tight junctions.group b coxsackieviruses (cvbs) must cross the epithelium as they initiate infection, but the mechanism by which this occurs remains uncertain. the coxsackievirus and adenovirus receptor (car) is a component of the tight junction and is inaccessible to virus approaching from the apical surface. many cvbs also interact with the gpi-anchored protein decay-accelerating factor (daf). here, we report that virus attachment to daf on the apical cell surface activates abl kinase, triggering rac-dependen ...200616413486
autoimmunity in coxsackievirus b3 induced myocarditis.virus infections are implicated in several autoimmune diseases. multiple mechanisms of autoimmunity induction have been proposed including antigenic mimicry, production of cryptic epitopes and infection acting as both adjuvant for self-antigens and the mechanism of releasing these cell antigens. evidence for these mechanisms in coxsackievirus b3 induced myocarditis is discussed.200616455582
molecular analysis of an echovirus 3 strain isolated from an individual concurrently with appearance of islet cell and ia-2 autoantibodies.growing evidence has implicated members of the genus enterovirus of the family picornaviridae in the etiology of some cases of type 1 diabetes (t1d). to contribute to an understanding of the molecular determinants underlying this association, we determined the complete nucleotide sequence of a strain of echovirus 3 (e3), human enterovirus b (hev-b) species, isolated from an individual who soon after virus isolation developed autoantibodies characteristic of t1d. the individual has remained posit ...200616455897
open sesame! coxsackieviruses conspire to trespass the tight junctional gate.in the january 13 issue of cell, coyne and bergelson describe an "open sesame!" strategy developed by coxsackieviruses to invade the organism through the intestinal epithelium. the strategy involves coopting intrinsic signaling abilities of the apical gpi-anchored protein daf to open the tight junction barrier, gain access to the primary receptor car, and activate virus internalization by a caveolin-dependent pathway.200616459291
[absence of echoviral rna sequences in medulla oblongata samples taken from patients who died of als].the role of viral infection in the pathogenesis of als has been raised many times in the previous papers. the presence of an enterovirus genome has previously been confirmed using pcr rt and pcr in situ in spinal cord tissue samples taken from patients who died of als. viral genome sequencing has also been used to show 91% and 88% homogeneity with echo 6 and 7 viruses, respectively. a year later the same method did not confirm the presence of the virus in spinal cord fragments taken from 30 pati ...200616463219
[the analysis of t cell receptor vbeta gene usage of cytolytic t-lymphocytes in coxsackievirus b3-induced myocarditis].to analyze the t cell receptor (tcr) vbeta gene usage of the cytolytic t-lymphocytes which result in immune-mediated myocyte injury in coxsackievirus b3-induced myocarditis.200616468649
detection of three porcine vesicular viruses using multiplex real-time primer-probe energy transfer.rapid identification of the etiologic agent in infected animals is important for the control of an outbreak of vesicular disease in livestock. we have in the present study developed a multiplex real-time reverse transcription-pcr, based on primer-probe energy transfer (priproet), for simultaneous detection and differentiation of three office international des epizooties (oie) classified vesicular viruses: foot-and-mouth disease virus, vesicular stomatitis virus and swine vesicular disease, causi ...200616472874
[influence of enteroviruses on metabolism of fatty acids in human embryo fibroblasts].the investigations on changes in metabolism of lipids--saturated and nonsaturated fatty acids in membranes of fibroblasts of the human embryo on a background of coxsackie b virus infection have been done. virus-induced changes of the lipid composition are indicated by a higher level of content of eicosatrienic and arachidonic pnfa, and a sum of nonsaturated and polynon saturated fatty acids. such phenomena (most expressed for serotypes of coxsackie b2, b3, b4 viruses) promote the increase of per ...200516493889
astragaloside iv exerts antiviral effects against coxsackievirus b3 by upregulating interferon-gamma.coxsackievirus b3 (cvb3) is a major pathogen for viral myocarditis and dilated cardiomyopathy in children and young adults. the aim of this study was to determine the antiviral effects of astragaloside iv against cvb3, and the underlying mechanism. first, we evaluated antiviral effects of astragaloside iv in vitro by measuring the virus titers of cvb3 in primarily cultured myocardial cells infected with cvb3, and in vivo by assessing the morbidity, mortality, heart-to-body weight ratio (hw/bw), ...200616495755
mrna translation is compartmentalized to the endoplasmic reticulum following physiological inhibition of cap-dependent translation.eukaryotic cells utilize a cycle of ribosome trafficking on the endoplasmic reticulum (er) to partition mrnas between the cytosol and er compartments. in this process, ribosomes engaged in the synthesis of signal sequence-bearing proteins are trafficked to the endoplasmic reticulum via the signal-recognition particle pathway and are released from the er upon translation termination. though the processes governing ribosome trafficking to the er are well understood, little is known regarding the c ...200616540694
decreased in vitro type 1 immune response against coxsackie virus b4 in children with type 1 diabetes.enteroviruses, particularly coxsackie virus b4 (cvb4), are considered to be involved in the pathogenesis of type 1 diabetes. we wanted to compare the characteristics of t-cell immune response to cvb4 in children with type 1 diabetes and healthy children with and without hla risk-associated haplotypes (hla-dr3-dq2 or hla-dr4-dq8) for type 1 diabetes. peripheral blood mononuclear cells (pbmcs) were isolated and cultured with cvb4 and analyzed for cytokine and chemokine receptors by flow cytometry ...200616567521
[expression of coxsackie-adenovirus receptor in hearts of mice with experimental viral myocarditis and its regulatory mechanism]. 200616624033
[inhibitory effect of cvb3-vp1 sirna on cvb3 replication].to inhibit the expression of cvb3 vp1 protein and the replication of cvb3 with synthesized sirnas.200616643786
xiao chai hu tang inhibits cvb1 virus infection of ccfs-1 cells through the induction of type i interferon 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 xiao chai hu tang (xcht), a popular herbal drug for treating viral and bacterial infections, against cvb1 infection and its mechanisms of action. our data showed that xcht neutralized the cvb1-induced cytopathic effect in human neonatal foreskin fibroblast cell line (ccfs-1 ...200616644487
ongoing coxsackievirus myocarditis is associated with increased formation and activity of myocardial immunoproteasomes.a growing body of evidence indicates that viral infections of the heart contribute to ongoing myocarditis and dilated cardiomyopathy. murine models of coxsackievirus b3 (cvb3)-induced myocarditis mimic the human disease and allow identification of susceptibility factors that modulate the course of viral myocarditis. susceptible mouse strains develop chronic myocarditis on the basis of restricted viral replication, whereas resistant strains recover after successful virus elimination. in comparati ...200616651621
the zinc containing pro-apoptotic protein siva interacts with the peroxisomal membrane protein pmp22.host answers to pathogen attacks define the course of pathogenic events and decide about the fate of the host organism. infection with coxsackievirus b3 (cvb3) can induce severe myocarditis and pancreatitis. the interplay between host factors and virus components is crucial for the fate of the infected host. as we have shown before, expression of the pro-apoptotic host protein siva is significantly increased after cvb3 infection, and infected cells are removed by programmed cell death. analysis ...200616683188
group b coxsackievirus diabetogenic phenotype correlates with replication efficiency.group b coxsackieviruses can initiate rapid onset type 1 diabetes (t1d) in old nonobese diabetic (nod) mice. inoculating high doses of poorly pathogenic cvb3/ga per mouse initiated rapid onset t1d. viral protein was detectable in islets shortly after inoculation in association with beta cells as well as other primary islet cell types. the virulent strain cvb3/28 replicated to higher titers more rapidly than cvb3/ga in the pancreas and in established beta cell cultures. exchange of 5'-nontranslat ...200616699045
cutting edge: t cell ig mucin-3 reduces inflammatory heart disease by increasing ctla-4 during innate immunity.autoimmune diseases can be reduced or even prevented if proinflammatory immune responses are appropriately down-regulated. receptors (such as ctla-4), cytokines (such as tgf-beta), and specialized cells (such as cd4+cd25+ t regulatory cells) work together to keep immune responses in check. t cell ig mucin (tim) family proteins are key regulators of inflammation, providing an inhibitory signal that dampens proinflammatory responses and thereby reducing autoimmune and allergic responses. we show i ...200616709797
antiviral flavans from the leaves of pithecellobium clypearia.two new antiviral flavan derivatives were isolated from a methanol extract of leaves of pithecellobium clypearia as guided by antiviral assays. the structures were characterized, by spectroscopic analyses, as 7-o-galloyltricetifavan (1) and 7,4'-di-o-galloyltricetifavan (2). cytopathic effect (cpe) reduction assay showed that both compounds 1 and 2 possess antiviral activity against respiratory syncytial virus (rsv), with 50% inhibition concentration (ic(50)) values of 5 and 10 microg/ml, respec ...200616724853
nucleotide sequences of ires domains iv and v of natural echo virus type 11 isolates with different replicative capacity phenotypes.echo viruses (ecv) belong to the enterovirus genus of the picornaviridae family and are the most frequently isolated from clinical and environmental samples. they are responsible for a wide variety of clinical syndromes involving most organs of the human body. we previously postulated that some of the variations in the recognition of echo virus type 11 (ecv 11) strains by a group specific monoclonal antibody (mab) which we have studied could be explained by variations in their replicative capaci ...200616732479
genetic variation of coxsackie virus b5 strains associated with aseptic meningitis in greece.in order to explore the genetic relationships among coxsackie virus b5 strains in greece, the nucleotide sequences of the partial vp1 gene in strains isolated from aseptic cases of meningitis were determined and compared with those of strains isolated from other countries. phylogenetic analysis showed a high degree of divergence (25%) among greek strains isolated in different years, which clustered with high bootstrap values in a different subgroup of viruses, suggesting that enterovirus types v ...200616774571
n- and 6-o-sulfated heparan sulfates mediate internalization of coxsackievirus b3 variant pd into cho-k1 cells.recently, it was demonstrated that the coxsackievirus b3 variant pd (cvb3 pd) is able to infect coxsackievirus-adenovirus receptor (car)-lacking cells by using heparan sulfates (hs) as additional receptors (a. e. zautner, u. korner, a. henke, c. badorff, and m. schmidtke, j. virol. 77:10071-10077, 2003). for this study, competition experiments with growth factors binding to known hs sequences as well as with specifically desulfated heparins were performed with chinese hamster ovary cells (cho-k1 ...200616775350
inhibition of protein trafficking by coxsackievirus b3: multiple viral proteins target a single organelle.despite replicating to very high titers, coxsackieviruses do not elicit strong cd8 t-cell responses, perhaps because antigen presentation is inhibited by virus-induced disruption of host protein trafficking. herein, we evaluated the effects of three viral nonstructural proteins (2b, 2bc, and 3a) on intracellular trafficking. all three of these proteins inhibited secretion, to various degrees, and directly associated with the golgi complex, causing trafficking proteins to accumulate in this compa ...200616775351
antiviral activity and constituent of ardisia chinensis benth against coxsackie b3 virus.ardisia chinensis benth is a medicinal plant traditionally used in the area of yao minority in southern china. the in vitro antiviral activities of extracts and fractions from ardisia chinensis were tested by the cytopathic effect (cpe) reduction assay in the present study. as a result, both the aqueous extract and the 95% ethanol extract of ardisia chinensis showed in vitro antiviral activity against coxsackie b3 (cox b3) virus to different extents, and the aqueous extract possessed more potent ...200616775812
in vitro screening of traditionally used medicinal plants in china against enteroviruses.to search for new antiviral agents from traditional chinese medicine, specifically anti-enteroviruses agents.200616810764
coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.coxsackievirus (cvb) infection is a significant cause of myocarditis and dilated cardiomyopathy (dcm). heart disease may be caused by direct cytopathic effects of the virus, a pathologic immune response to persistent virus, or autoimmunity triggered by the viral infection. cvb interacts with its host at multiple stages during disease development. signaling through viral receptors may alter the intracellular environment in addition to facilitating virus entry. viral genetic determinants that enco ...200616817756
decay-accelerating factor (cd55) promotes cd1d expression and vgamma4+ t-cell activation in coxsackievirus b3-induced myocarditis.balb/c mice infected with the h3 variant of coxsackievirus b3 (cvb3) develop severe myocarditis which is initiated by up-regulation of cd1d during infection and cd1d-dependent activation of t cells expressing the vgamma4 t cell receptor. previous studies have shown that a mutant variant of the h3 virus which shows reduced binding avidity to one of the known cvb3 virus receptors, decay accelerating factor (daf), fails to up-regulate cd1d or activate vgamma4+ cells. to determine if daf has a role ...200616817758
[molecular characterization and phylogenetic analysis of enteroviruses inducing the outbreaks and seasonal rises of morbidity in different regions of the republic of belarus].as shown by the results of the analysis, viruses echo 30 circulating over the period of the last 8 years in belarus, belonged to 3 different genetic subtypes which earlier or simultaneously circulated in other european states. the outbreaks of enterovirus infections (evi) were facilitated by the appearance of a genetic viral subtype, relatively "new" for human population, and which had not earlier circulated on this territory. thus, the development of outbreak morbidity in 2003 was caused by a c ...200616830583
development of a real-time pcr assay based on primer-probe energy transfer for the detection of swine vesicular disease virus.a real-time pcr assay based on primer-probe energy transfer (priproet) was developed to detect swine vesicular disease virus (svdv). specificity tests of svdv and heterologous virus showed specific amplification of svdv strains only. the amplification plot for the closely related coxsackievirus b5 remained negative. the sensitivity of assay was five copies of viral genome equivalents. a key point of the assay is tolerance toward mutations in the probe region. melting curve analysis directly afte ...200616835700
molecular typing of enteroviruses associated with viral meningitis in cyprus, 2000-2002.human enteroviruses are responsible for a wide spectrum of clinical diseases affecting many different organ systems. although infection is usually asymptomatic, infections of the central nervous system manifested as meningitis or encephalitis can pose a serious public health problem, especially during outbreaks. in this study, samples from 218 patients diagnosed with enteroviral meningitis between january 2000 and december 2002 were analysed in order to assess the epidemiology of human enterovir ...200616849723
[investigation of viral pathogens contributing to habitual abortion].to investigate the association of coxsackie b virus (cbv) with habitual abortion.200616864103
idiopathic dilated cardiomyopathy as a late complication of healed viral (coxsackie b virus) myocarditis: historical analysis, review of the literature, and a postulated unifying hypothesis.a historically based literature review of the relationship between acute viral myocarditis and the subsequent development of a dilated cardiomyopathic state is presented. a strong emphasis on a state of definitional ambiguity in the literature as regards the timing of the myopathic state following a viral infection is noted, i.e. does the myopathic state develop acutely and concomitantly with viral myocarditis due to overwhelming viral mediated myocardial cell necrosis, subacutely due to negativ ...200616867849
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
proteome alterations in human host cells infected with coxsackievirus b3.coxsackievirus b3 (cvb3) is a common factor in human myocarditis. the interplay between host factors and virus components is crucial for the fate of the infected cells. despite that, host protein responses, which characterize cvb3-induced diseases, have not yet been determined in detail. to investigate the nature of modified protein patterns in infected human cells compared with uninfected cells, two-dimensional gel electrophoresis in combination with matrix-assisted laser desorption/ionization- ...200616894202
validation of rt-pcr assays for molecular characterization of porcine teschoviruses and enteroviruses.porcine enteroviruses (pevs) and teschoviruses (ptvs) are described as causative agents of neurological disorders, fertility disorders and dermal lesions of swine. difficulties in the serological detection of these viruses may lead to a significant underestimation of infections with clinical symptoms. with the recent availability of genome sequence data for all the serotypes, molecular diagnosis is a possibility. the present study describes a new approach to molecular 'serotyping' of ptvs and pe ...200616907956
effects of the sabin-like mutations in domain v of the internal ribosome entry segment on translational efficiency of the coxsackievirus b3.the domain v within the internal ribosome entry segment (ires) of poliovirus (pv) is expected to be important in its own neurovirulence because it contains an attenuating mutation in each of the sabin vaccine strains. in this study, we try to find out if the results observed in the case of sabin vaccine strains of pv can be extrapolated to another virus belonging to the same genus of enteroviruses but with a different tropism. to test this hypothesis, we used the coxsackievirus b3 (cvb3), known ...200616909284
treatment of coxsackievirus-b3-infected balb/c mice with the soluble coxsackie adenovirus receptor car4/7 aggravates cardiac injury.coxsackie adenovirus receptor (car) is involved in immunological processes, and its soluble isoforms have antiviral effects on coxsackievirus b3 (cvb3) infection in vitro. we explored in this study the impact of car4/7, a soluble car isoform, on cvb3-induced myocarditis in balb/c mice. balb/c mice were treated daily with recombinant car4/7, beta-galactosidase (beta-gal; as control protein) or buffer for 9 days. half of each group was infected with cvb3 on day 3, and all mice were killed on day 9 ...200616924471
high prevalence of human enterovirus a infections in natural circulation of human enteroviruses.human enterovirus (hev) infections can be asymptomatic or cause only mild illness; recent evidence may implicate hev infection in type 1 diabetes mellitus and myocarditis. here, we report the molecular characterization of hev obtained in serial monthly collections from healthy norwegian infants. a total of 1,255 fecal samples were collected from 113 healthy infants beginning at age 3 months and continuing to 28 months. the samples were analyzed for hev nucleic acid by real-time pcr. fifty-eight ...200616943351
fdjs03 isolates causing an outbreak of aseptic meningitis in china that evolved from a distinct echovirus 30 lineage imported from countries of the commonwealth of independent states.we compared echovirus 30 strains (fdjs03) which caused an outbreak of aseptic meningitis in china in 2003 with other human enterovirus b strains. sequencing of the complete genome of fdjs03_84, a representative strain from this outbreak, revealed a mosaic structure with a putative recombination spot within the 2b gene. it was most similar to a strain of the same serotype, e30-14125-00, in the 5' half of the genome but was almost equidistant to all strains analyzed in most of the 3' half of the g ...200616957029
molecular epidemiology of echoviruses 11 and 13, based on an environmental surveillance conducted in toyama prefecture, 2002-2003.nineteen echovirus 11 (e11) and 12 e13 isolates were isolated from three rivers in toyama prefecture, japan, during an environmental surveillance conducted from april 2002 to march 2003. the nucleotide sequences of e13 isolates were closely related to those from patients with aseptic meningitis, with less than 1.3% divergence in the vp1 region of the viral capsid gene, and belonged to the same clade responsible for a worldwide outbreak that started in 2000. in contrast, e11 isolates were cluster ...200616957267
induction of the chemokine interferon-gamma-inducible protein-10 in human pancreatic islets during enterovirus infection.enterovirus infections have long been suspected to be environmental factors that may cause type 1 diabetes, but the pathways leading from infection to beta cell destruction are still unknown. we therefore examined whether enterovirus infection of human islets leads to upregulation of interferon-gamma-inducible protein (ip-10, now known as chemokine [c-x-c motif] ligand 10 [cxcl10]), a chemokine important for the induction of insulitis.200616969644
renal effects of coxsackie b4 virus in hyper-iga mice.for clarification of the pathogenetic role of viral infection in chronic glomerulonephritis, the renal effects of coxsackie b4 virus (cb4) were examined in hyper-iga (higa) mice. in experiment 1, higa mice (n = 75) were inoculated intravenously with live cb4 and inactivated cb4 once a month from 1 to 12 mo of age. in experiment 2, higa mice (n = 45) were inoculated intravenously with live cb4 and inactivated cb4 once at 6 wk of age. in experiment 3, 60 mice were inoculated intravenously with car ...200616971656
analysis of the genetic and the corresponding antigenic variability of the vp1 3' end of echo virus type 11 and echo virus type 30.the enteroviruses (ev), rna viruses belonging to the picornaviridae family, have a high genetic variability due to the absence of the efficient proofreading and post replicative repair activities associated with the rna polymerase. in the present work, we studied the genetic and the antigenic variability of echo virus types 11 (e11) and 30 (e30), which are the most isolated echoviruses serotypes in clinical and environmental samples. we established on the 3' end of the vp1 gene, consensus sequen ...200616972035
[molecular identification and genetic analysis of an echovirus 19-associated epidemic of aseptic encephalitis].to ascertain the pathogen of aseptic encephalitis epidemic in long-yan city in fujian, and to find out the genetic characteristics of the virus.200616981328
molecular and epidemiologic analysis of enterovirus b neurological infection in argentine children.human enteroviruses are one of the major causes of central nervous system (cns) infections in pediatrics.200616982209
inhibition of coxsackievirus b3 in cell cultures and in mice by peptide-conjugated morpholino oligomers targeting the internal ribosome entry site.coxsackievirus b3 (cvb3) is a primary cause of viral myocarditis, yet no effective therapeutic against cvb3 is available. nucleic acid-based interventional strategies against various viruses, including cvb3, have shown promise experimentally, but limited stability and inefficient delivery in vivo remain as obstacles to their potential as therapeutics. we employed phosphorodiamidate morpholino oligomers (pmo) conjugated to a cell-penetrating arginine-rich peptide, p007 (to form ppmo), to address ...200616987987
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
coxsackievirus b3 induces t regulatory cells, which inhibit cardiomyopathy in tumor necrosis factor-alpha transgenic mice.innate immunity promotes both the generation of autoimmunity and immunoregulation of adaptive immunity. transgenic mice expressing the tumor necrosis factor-alpha (tnf-alpha) gene under the cardiac myosin promoter (tnf1.6 mice) develop dilated cardiomyopathy. transgenic mice show extensive cardiac inflammation, suggesting that immunopathogenic mechanisms may promote cardiomyopathy. two coxsackievirus b3 (cvb3) variants infect and replicate in the heart. h3 variant is highly myocarditic, but h310 ...200617038643
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
prospective identification of hev-b enteroviruses during the 2005 outbreak.enteroviruses (evs) represent the main etiological agents of epidemics of viral meningitis and especially the serotypes related to the human enterovirus b species. genetic typing by sequencing a pcr-amplified portion of the genome has proved to be useful for identifying evs and is more rapid than standard seroneutralization tests. however, prospective genotyping has not been reported in routine practice within a clinical diagnostic laboratory. a genetic typing assay using two sets of primers was ...200617063526
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
rt-pcr and cell culture infectivity assay to detect enteroviruses during drinking water treatment processes.in this study, 62 water samples were collected from two water treatment plants (wtps) in suez canal cities (port said and ismaillia) and one plant in cairo (giza wtp) in addition to the beginning of the two nile river branches (rosetta and damietta). viruses were concentrated by adsorption-elution ethod sing 142 mm-diameter nitrocellulose membrane of 0.45 microm pore size and eluted with 3% beef extract at ph 9.5. the concentrated samples were inoculated for 3 successive passages in three cell c ...199917219867
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
the role of coxsackieviruses infection in the children of insulin dependent diabetes mellitus.in the present study, there were two groups of diabetic patients. the first group was newly diagnosed diabetic patients of less than one year duration of disease. they were 40 patients. the second group was diabetic patients with more than one year duration of disease. they were 30 patients. the control group was 30 normal healthy children. evidence of virus infection was detected by tissue culture isolation, neutralization test, rt-pcr, igm, and igg specific antibodies for coxsackie b viruses. ...200317265619
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
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