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specific interactions of hela cell proteins with coxsackievirus b3 rna: la autoantigen binds differentially to multiple sites within the 5' untranslated region.translation initiation of the coxsackievirus b3 (cvb3) rna occurs by internal ribosomal entry. the internal ribosomal entry site (ires) of the virus has been mapped to the 5' untranslated region (5' utr) of the genome. as well, the 5' utr has been suggested to play roles in determining the tissue tropism and infectivity of the virus. in this study, we investigated interactions between hela cell protein extracts and radiolabeled rna of cvb3 5' utr by competitive uv cross-linking. we have observed ...200212457960
a shine-dalgarno-like sequence mediates in vitro ribosomal internal entry and subsequent scanning for translation initiation of coxsackievirus b3 rna.translation initiation of coxsackievirus b3 (cvb3) rna is directed by an internal ribosome entry site (ires) within the 5' untranslated region. however, the details of ribosome-template recognition and subsequent translation initiation are still poorly understood. in this study, we have provided evidence to support the hypothesis that 40s ribosomal subunits bind to cvb3 rna via basepairing with 18s rrna in a manner analogous to that of the shine-dalgarno (s-d) sequence in prokaryotic systems. we ...200312504538
[effect of combined treatment of shuanghuanglian and recombinant interferon alpha 2a on coxsackievirus b3 replication in vitro].to investigate the effect of combined treatment of shanghanglian (shhl) and recombinant interferon alpha 2a on coxsackie virus b3 replication.200012525074
coxsackievirus b3-associated myocardial pathology and viral load reduced by recombinant soluble human decay-accelerating factor in mice.coxsackievirus b3 (cvb3) infection can result in myocarditis, which in turn may lead to a protracted immune response and subsequent dilated cardiomyopathy. human decay-accelerating factor (daf), a binding receptor for cvb3, was synthesized as a soluble igg1-fc fusion protein (daf-fc). in vitro, daf-fc was able to inhibit complement activity and block infection by cvb3, although blockade of infection varied widely among strains of cvb3. to determine the effects of daf-fc in vivo, 40 adolescent a/ ...200312533688
genetic determinants of coxsackievirus b3 pathogenesis.the development of high throughput genomic and bioinformatic analysis tools, coupled with established molecular techniques, has allowed new insights into the pathogenesis of infectious diseases. in humans, coxasackievirus b3 (cvb3) is the primary etiological agent of viral myocarditis, an inflammatory disease process involving the heart muscle. early host cellular survival and apoptotic mechanisms during viral infections, as well as immune events, affect myocarditis progression and outcome. ther ...200212538163
the study on intramyocardial calcium overload and apoptosis induced by coxsackievirus b3.the isolated cardiac myocytes of rats were immediately infected by cosackievirus b3 (cvb3) to investigate the effects of such procedure on the cell cycle, apoptosis and intracellular ionized calcium (ca2+ i) of cardiac myocytes. newborn balb/c murine cardiac myocytes were cultivated, then infected by cvb3. intracellular ca2+ i was measured by flow cytometer. the calcium in the medium for culturing cardiac myocytes was detected by using atom absorb spectrum test. it was found that cvb3 could mark ...200112539594
[coxsackievirus b3 infection and keshan disease].to study the relationship between the infection of enteroviruses and the etiology of keshan disease, we examined the 30 blood samples from the latent-chronic kd patients from mianning, xider, derchang county of sichuan province with lde-pcr (long distance enterovirus-specific rt pcr), two sensitive and specific elisas (one for cvb1-6 igm and the other for cvb1-6 igg), and three-primer rt pcr specific for cvb3. results show that: 1) the infection rate of enteroviruses in the samples from the late ...200212600035
trace element changes in the pancreas during viral infection in mice.the trigger for some cases of juvenile diabetes has been suggested to be an interaction between a virus and various trace elements. infection with human coxsackievirus b3 (cb3) in the murine model results in viral replication and inflammation in the pancreas.200312604919
role of cd1d in coxsackievirus b3-induced myocarditis.the myocarditic (h3) variant of coxsackievirus b3 (cvb3) causes severe myocarditis in balb/c mice and balb/c mice lacking the invariant j alpha 281 gene, but minimal disease in balb/c cd1d(-/-) animals. this indicates that cd1d expression is important in this disease but does not involve the invariant nkt cell often associated with cd1d-restricted immunity. the h3 variant of the virus increases cd1d expression in vitro in neonatal cardiac myocytes whereas a nonmyocarditic (h310a1) variant does n ...200312626572
caspase-3 activation and erk phosphorylation during cvb3 infection of cells: influence of the coxsackievirus and adenovirus receptor and engineered variants.caspase activation and map kinase signaling have been implicated in coxsackievirus b3 (cvb3) pathogenesis, and both have been demonstrated late in the virus life cycle. we studied activation of caspase-3, an effector protease of apoptosis, and erk phosphorylation, indicative of mapk signaling pathway activation, following cvb3 infection of cells that express the coxsackievirus and adenovirus receptor (car) or car constructs lacking the cytoplasmic domain, and cells which express no detectable ca ...200312686427
crystal structure of swine vesicular disease virus and implications for host adaptation.swine vesicular disease virus (svdv) is an enterovirus of the family picornaviridae that causes symptoms indistinguishable from those of foot-and-mouth disease virus. phylogenetic studies suggest that it is a recently evolved genetic sublineage of the important human pathogen coxsackievirus b5 (cbv5), and in agreement with this, it has been shown to utilize the coxsackie and adenovirus receptor (car) for cell entry. the 3.0-a crystal structure of strain uk/27/72 svdv (highly virulent) reveals th ...200312692248
extending the family of uncg-like tetraloop motifs: nmr structure of a cacg tetraloop from coxsackievirus b3.stable rna tetraloop motifs are found frequently in biologically active rnas. these motifs carry out a wide variety of functions in rna folding, in rna-rna and rna-protein interactions. a great deal of knowledge about the structures and functions of tetraloop motifs has accumulated largely due to intensive theoretical, biochemical, and biophysical studies on three most frequently occurring families of tetraloop sequences, namely, the cuncgg, the cgnrag, and the gcuugc sequences. our knowledge su ...200312693932
beta2-microglobulin-associated regulation of interferon-gamma and virus-specific immunoglobulin g confer resistance against the development of chronic coxsackievirus myocarditis.to gain insight into the strategies of the immune system to confer resistance against the development of chronic coxsackievirus b3 (cvb3) myocarditis we compared the course of the disease in c57bl/6 mice, beta2-microglobulin knockout (beta2m(-/-)) mice, and perforin-deficient (perforin(-/-)) mice. we found that perforin(-/-) mice as well as immunocompetent c57bl/6 mice reveal a resistant phenotype with complete elimination of the virus from the heart in the course of acute myocarditis. in contra ...200312707055
il-12 receptor beta 1 and toll-like receptor 4 increase il-1 beta- and il-18-associated myocarditis and coxsackievirus replication.th1-type immune responses, mediated by il-12-induced ifn-gamma, protect the host from most viral infections. to investigate the role of il-12 and ifn-gamma on the development of coxsackievirus b3 (cb3)-induced myocarditis, we examined the level of inflammation, viral replication, and cytokine production in il-12rbeta1- and ifn-gamma-deficient mice following cb3 infection. we report that il-12rbeta1 deficiency results in decreased viral replication and inflammation in the heart, while ifn-gamma d ...200312707353
sequential changes in fe, cu, and zn in target organs during early coxsackievirus b3 infection in mice.in coxsackievirus b3 (cb3) infection, the heart and pancreas are major target organs and, as a general host response, an associated immune activation and acute phase reaction develops. although iron (fe), copper (cu), and zinc (zn) are involved in these responses, sequential trace element changes in different target organs of infection have not been studied to date. in the present study, fe, cu, and zn were measured through inductively coupled plasma mass spectrometry (icp-ms) in the plasma, liv ...200312719606
the stem loop ii within the 5' nontranslated region of clinical coxsackievirus b3 genomes determines cardiovirulence phenotype in a murine model.coxsackievirus b3 (cvb3) is a principal viral cause of acute myocarditis in humans and has been implicated in the pathogenesis of dilated cardiomyopathy. it has been demonstrated elsewhere that, for 2 wild-type cvb3 strains, the primary molecular determinant of cardiovirulence phenotype localizes to the 5' nontranslated region (5' ntr). here in this study, through construction of cvb3 chimeras, the predicted stem loop (sl) ii within the 5' ntr has been identified as a primary viral determinant o ...200312721935
coxsackievirus b3-resistant mice become susceptible in se/vitamin e deficiency.the severity of the heart damage caused by a coxsackievirus infection in mice is determined by several factors, including the genotype of the infecting virus as well as the genetic background of the infected host. earlier work by us showed that the cardiovirulence of a given coxsackievirus genotype could be increased substantially by feeding the host a diet nutritionally deficient in either selenium or vitamin e. here we report that host genetic background as a determinant of viral infection out ...200312726914
selenium deficiency and viral infection.the discovery that the juvenile cardiomyopathy known as keshan disease likely has a dual etiology that involves both a nutritional deficiency of the essential trace mineral selenium (se) as well as an infection with an enterovirus provided the impetus for additional studies of relationships between nutrition and viral infection. an amyocarditic strain of coxsackievirus b3, cvb3/0, converted to virulence when it was inoculated into se-deficient mice. this conversion was accompanied by changes in ...200312730444
coxsackievirus b3 sequences in the blood of a neonate with congenital myocarditis, plus serological evidence of maternal infection.a fatal case of myocarditis in a neonate is described. the clinical features were evident at birth, and enteroviral rna was detected in the blood of the baby on the day of birth and again 10 days later by a generic enterovirus nested reverse transcription-polymerase chain reaction (rt-pcr) assay. the enterovirus rna was subsequently retested by a separate, newly developed nested rt-pcr assay yielding a pcr product within the vp1 coding region suitable for sequencing. identical 239-base pair sequ ...200312794724
overexpression of interferon-gamma-inducible gtpase inhibits coxsackievirus b3-induced apoptosis through the activation of the phosphatidylinositol 3-kinase/akt pathway and inhibition of viral replication.our previous studies using differential mrna display have shown that interferon-gamma-inducible gtpase (igtp), was up-regulated in coxsackievirus b3 (cvb3)-infected mouse hearts. in order to explore the effect of igtp expression on cvb3-induced pathogenesis, we have established a doxycycline-inducible tet-on hela cell line overexpressing igtp and have analyzed activation of several signaling molecules that are involved in cell survival and death pathways. we found that following igtp overexpress ...200312819192
identification of enteroviruses by using monoclonal antibodies against a putative common epitope.a common epitope region of enteroviruses was identified by sequence-independent single-primer amplification (sispa), followed by immunoscreening of 11 cdna libraries from two korean enterovirus isolates (echoviruses 7 and 30) and a coxsackievirus b3 (atcc-vr 30). the putative common epitope region was localized in the n terminus of vp1 when the displayed recombinant proteins from the phages were chased by the convalescent-phase sera. the genomic region encoding the common epitope region was ampl ...200312843038
coxsackievirus b3-induced apoptosis and caspase-3.cell death can be classified into two categories: apoptosis and necrosis. apoptotic pathway can be either caspase-dependent or caspase-independent. caspase-independent cytopathic effect (cpe) has been described. in order to evaluate the pattern of hela cell death induced by coxsackievirus b3 (cvb3) and whether apoptosis involves caspase activation, we co-cultivated hela cells with cvb3 and detected the cytopathic changes, the alteration of mrna and protein expression of caspase-3 gene plus caspa ...200312862321
coxsackievirus b3 induces apoptosis in the early phase of murine myocarditis: a comparative analysis of cardiovirulent and noncardiovirulent strains.to investigate the relationship between enteroviral infection and myocardial tissue apoptosis during the development of viral myocarditis in a murine model.200312867750
proteasome inhibition reduces coxsackievirus b3 replication in murine cardiomyocytes.coxsackievirus is the most prevalent virus associated with the pathogenesis of myocarditis and its sequela dilated cardiomyopathy. we have previously shown that coxsackievirus infection facilitates the ubiquitin/proteasome processing of the cell-cycle protein cyclin d1 and the tumor suppressor p53, which raises the possibility that the ubiquitin/proteasome pathway may be used by virus to promote viral replication. in this study, we examined the interplay between coxsackievirus replication and th ...200312875959
effect of coxsackievirus b3 on ion channel currents in rat ventricular myocytes.to investigate the effects of coxsackievirus b3(cvb3) on ion channel currents in rat ventricular myocytes.200012903773
dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside.genetic defects of the dystrophin-glycoprotein complex (dgc) cause hereditary dilated cardiomyopathy. enteroviruses can also cause cardiomyopathy and we have previously described a mechanism involved in enterovirus-induced dilated cardiomyopathy: the enteroviral protease 2a directly cleaves dystrophin in the hinge 3 region, leading to functional dystrophin impairment. during infection of mice with coxsackievirus b3, the dgc in the heart is disrupted and the sarcolemmal integrity is lost in virus ...200412920582
heparan sulfates and coxsackievirus-adenovirus receptor: each one mediates coxsackievirus b3 pd infection.amino acid exchanges in the virus capsid protein vp1 allow the coxsackievirus b3 variant pd (cvb3 pd) to replicate in decay accelerating factor (daf)-negative and coxsackievirus-adenovirus receptor (car)-negative cells. this suggests that molecules other than daf and car are involved in attachment of this cvb3 variant to cell surfaces. the observation that productive infection associated with cytopathic effect occurred in chinese hamster ovary (cho-k1) cells, whereas heparinase-treated cho-k1 ce ...200312941917
bcl-2 and bcl-xl overexpression inhibits cytochrome c release, activation of multiple caspases, and virus release following coxsackievirus b3 infection.coxsackievirus b3, a cytopathic virus in the family picornaviridae, induces degenerative changes in host cell morphology. here we demonstrate cytochrome c release and caspases-2, -3, -6, -7, -8, and -9 processing. enforced bcl-2 and bcl-xl expression markedly reduced release of cytochrome c, presentation of the mitochondrial epitope 7a6, and depressed caspase activation following infection. in comparison, cell death using trail ligand caused caspase-8 processing prior to cytochrome c release and ...200312951029
isolation of a peptide inhibitor of human rhinovirus.cell culture-based transdominant genetic techniques provide new methods for discovering peptide/rna modulators of cellular pathways. we applied this technology to isolate a peptide inhibitor of human rhinovirus. a green fluorescent protein (gfp)-scaffolded library of cdna fragments was expressed in hela cells from a retroviral vector and screened for inhibitors of rhinovirus-mediated cell killing. a dna clone, i421, increased cell survival in an hrv14 challenge assay from less than 0.5% to great ...200312951031
characterization of coxsackievirus b3-caused apoptosis under in vitro conditions.among several mechanisms of pathogenesis of the frequent and sometimes serious infections with coxsackievirus b3 (cvb3), one detail is apoptosis. recently, a new apoptotic mechanism involving the specific interaction between the capsid protein vp2 of the highly virulent variant cvb3h3 and the proapoptotic host protein siva was identified. the relevance of this observation for virus pathogenicity was shown in a balb/c mouse model using cvb3h3 and the interaction-deficient mutant virus cvb3h310a1. ...200413680215
interferons in enteroviral heart disease: modulation of cytokine expression and antiviral activity.interferon (ifn)-beta has a more than 120-fold higher antiviral activity than the closely related ifn-alpha in human myocardial fibroblasts infected with the cardiotropic enterovirus coxsackievirus b3 (cvb3). cvb3 replication induces interleukin (il)-6 and il-8 expression in myocardial fibroblasts, and suppresses the expression of monocyte chemoattractant protein-1 (mcp-1). we investigated whether the higher antiviral activity of ifn-beta compared to ifn-alpha was a result of a suppression of il ...200413680216
location and regeneration of enteriovirus receptors of hela cells.zajac, ihor (hahnemann medical college, philadelphia, pa.), and richard l. crowell. location and regeneration of enterovirus receptors of hela cells. j. bacteriol. 89:1097-1100. 1965.-treatment of live hela cells with chymotrypsin or trypsin completely inactivated the viral receptors for coxsackievirus b3 and poliovirus t1, respectively. enzyme-treated cells regained their enterovirus receptor activity after incubation in culture medium. the existence of intracellular receptors for virus could n ...196514279119
cardiomyocyte apoptosis in experimental coxsackievirus b3 myocarditis.viruses are known to induce apoptosis in their host cells. we studied whether cardiomyocyte apoptosis occurs upon coxsackievirus b3 (cvb3) infection and whether virus-associated apoptosis plays a role in the pathogenesis of experimental myocarditis.200314507574
coxsackievirus b3 and the neonatal cns: the roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease.neonates are particularly susceptible to coxsackievirus infections of the central nervous system (cns), which can cause meningitis, encephalitis, and long-term neurological deficits. however, viral tropism and mechanism of spread in the cns have not been examined. here we investigate coxsackievirus b3 (cvb3) tropism and pathology in the cns of neonatal mice, using a recombinant virus expressing the enhanced green fluorescent protein (egfp). newborn pups were extremely vulnerable to coxsackieviru ...200314507646
nitric oxide donors inhibit the coxsackievirus b3 proteinases 2a and 3c in vitro, virus production in cells, and signs of myocarditis in virus-infected mice.the antiviral effect of nitric oxide (no)-releasing compounds was investigated. using bacterially expressed and purified proteinases 2a and 3c of coxsackievirus b3, in vitro assays demonstrated the inhibition of the 2a proteinase activity in the presence of s-nitroso- n-acetyl-penicillamine (snap), 3-morpholinosydnonimine (sin-1), 4-phenyl-3-furoxancarbonitrile (pfc), glyceryl trinitrate (gtn), and isosorbide dinitrate (isdn). sodium nitroprusside (snp), which releases no after metabolization, h ...200414513374
mechanisms of alcoholic pancreatitis. proceedings of a conference. chicago, illinois, usa, november 2002.long-term, heavy alcohol consumption is associated with both acute and chronic pancreatitis. progression of pancreatitis may lead to multiple comorbidities including maldigestion, diabetes, and pancreatic cancer. understanding the underlying molecular, biochemical, and cellular mechanisms by which alcohol ingestion leads to the development of pancreatitis may help to develop strategies for the treatment and prevention of the disease. the national institute on alcohol abuse and alcoholism and the ...200314576487
animal model of alcoholic pancreatitis: role of viral infections.pancreatitis is clearly associated with alcohol abuse, but only a relatively small percentage of people who abuse alcohol develops obvious pancreatitis. these observations have led to the concept that the development of alcoholic pancreatitis requires cofactors. although diet and smoking have been studied, a clear cofactor has not been identified. the study results presented in this paper were obtained to determine whether viral infection of the pancreas would be a cofactor for alcoholic pancrea ...200314576491
risks versus benefits of nsaids including aspirin in myocarditis: a review of the evidence from animal studies.nsaids, including aspirin (acetylsalicylic acid), are frequently used and effective in a broad variety of inflammatory diseases, i.e. rheumatic carditis and pericarditis. myocarditis may constitute another suitable indication for nsaids in order to relieve the symptoms of the presumed viral infection or because pericardial effusion is often associated with this condition. however, concerns have been raised about their indiscriminate use in myocarditis. to clarify this issue, we conducted a syste ...200314583071
direct interferon-gamma-mediated protection caused by a recombinant coxsackievirus b3.coxsackievirus b3 (cvb3) is one of the most important causes of viral myocarditis. cytokines are involved in the control of cvb3 replication and pathogenesis. local expression of specific cytokines by recombinant cvb3 confers prevention of virus-caused myocarditis. expression of ifn-gamma by cvb3(ifn-gamma) protected balb/c and c57bl/6 mice when the lethal infection with the highly pathogenic cvb3h3 variant was given directly after or prior to cvb3(ifn-gamma) inoculation by decreasing the viral ...200314585336
coxsackievirus b3-induced myocarditis: differences in the immune response of c57bl/6 and balb/c mice.coxsackievirus b3 (cvb3) infections are the most frequent causes of human myocarditis, often resulting in chronic stages characterized by fibrosis and loss of function. this disease is called dilated cardiomyopathy (dcm). persistent virus in the myocardium may lead to chronic activation of fibroblasts, and subsequently, to fibrosis of the myocardium. studies with immunodeficient mice have shown that certain defects of the immune system retard the rate at which virus is eliminated from the heart, ...200414593475
quantitative multiplex real-time pcr for the sensitive detection of interferon beta gene induction and viral suppression of interferon beta expression.interferon-beta (ifn-beta) protein and activity can be detected by enzyme immunoassays and biological assays. however, precise quantification of low ifn-beta mrna concentrations, which is advantageous for investigating ifn-beta gene expression in small tissue samples or during the early stage of a virus infection, remains a challenge. therefore, we established a quantitative real-time pcr (qpcr) for ifn-beta and the housekeeping gene porphobilinogen deanimase (pbgd) in separated assays as well a ...200314596815
an in vivo model of autoimmune post-coxsackievirus b3 myocarditis in severe combined immunodeficiency mouse.severe combined immunodeficiency (scid) mice possess neither t nor b lymphocytes and are thus suitable recipients for adoptively transferred lymphocytes. because autoimmune mechanisms may be involved in the pathogenesis of coxsackievirus b3 (cb3) myocarditis, we attempted to assess the in vitro cellular damage caused by antigen-sensitized lymphocytes and to determine whether splenic lymphocytes from balb/c mice with chronic cb3 myocarditis could cause myocarditis into scid mice.200314613869
transfection of prion protein gene suppresses coxsackievirus b3 replication in prion protein gene-deficient cells.the susceptibility of prion protein gene (prnp)-null cells to coxsackievirus b3 (cvb3) was investigated. primary cultures of murine prnp(-/-) brain cells were more sensitive to cvbs than corresponding cells from wild-type mice. the viral susceptibility of a prnp-null cell line (hpl3-4) derived from the murine hippocampus was compared with that of two established cell lines (hela and hep-2) that are widely employed for cvb3 studies. after infection with cvb3, hpl3-4 cells showed a very rapid and ...200314645931
coxsackievirus b3 infection compromises endothelial-dependent vasodilation of coronary resistance arteries.the mechanisms of coronary artery dysfunction in coxsackievirus b3 (cvb3)-mediated viral myocarditis are poorly understood. we used pressure myography of mouse septal coronary arteries to determine the early and late effects of cvb3 infection on vascular function. male cd-1 mice (age 6-7 weeks) were infected with cvb3 (1.75 x 10(10) pfu, i.p.). control mice were injected with pbs. mice were killed at 3, 7, and 42 days post infection, and the ventricular septal artery was dissected and mounted on ...200414668566
mice deficient for the ets transcription factor elk-1 show normal immune responses and mildly impaired neuronal gene activation.the transcription factor elk-1 belongs to the ternary complex factor (tcf) subfamily of ets proteins. tcfs interact with serum response factor to bind jointly to serum response elements in the promoters of immediate-early genes (iegs). tcfs mediate the rapid transcriptional response of iegs to various extracellular stimuli which activate mitogen-activated protein kinase signaling. to investigate physiological functions of elk-1 in vivo, we generated elk-1-deficient mice by homologous recombinati ...200414673163
vaccination procedures against coxsackievirus-induced heart disease.coxsackievirus b3--a member of the picornavirus family--is one of the major causes of virus-induced acute or chronic heart disease. despite the fact that the molecular structure of this pathogen has been characterized very precisely during the last 10 years, until recently, there was no virus-specific preventive or therapeutic procedure against coxsackievirus b3-induced human heart disease in clinical use. however, using different murine model systems it has been demonstrated that classic as wel ...200314711363
induction of chemokines in human astrocytes by picornavirus infection requires activation of both ap-1 and nf-kappa b.infection with different picornaviruses can cause meningitis/encephalitis in humans and experimental animals. to investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astrocytes was investigated following infection with theiler's murine encephalomyelitis virus (tmev), coxsackievirus b3 (cvb3), or coxsackievirus b4 (cvb4). we report that all these viruses are potent inducers for the expression of interleukin-8 (il-8) and monocyte chemoattractant pr ...200414730702
in vitro antiviral activity of bael (aegle marmelos corr) upon human coxsackieviruses b1-b6.the in-vitro antiviral activity of a series of compounds in samples extracted from various parts of the indian holy tree, bael (aegle marmelos corr.) were evaluated for their efficacy against human coxsackieviruses b1-b6. the inhibitory concentrations (ic50) for leaves (l1 and l2) stem and stem bark (s1, s2, s3 and s4) fruit (f1 and f2micro) root and root bark (r1 and r2) and pure compound, the marmelide were 1000 microg/ml (for l1 and l2), 1000 microg/ml (for s1, s2, s3 and s4), 1000 microg/ml ...200214768825
autoimmune disease 2002: an overview.autoimmune disease includes a large spectrum of clinically distinct entities that share a common etiology, a misguided, self-directed immune response. collectively, they are major contributors to morbidity and mortality. normally, the body utilizes a number of strategies to avoid the pathologic consequences of autoimmune reactions, but these defenses may fail for a combination of hereditary and environmental factors. infection has long been regarded as a common environmental trigger of autoimmun ...200414870977
the structure of the stemloop d subdomain of coxsackievirus b3 cloverleaf rna and its interaction with the proteinase 3c.stemloop d (sld) of the 5' cloverleaf rna is the cognate ligand of the coxsackievirus b3 (cvb3) 3c proteinase (3cpro). both are indispensable components of the viral replication initiation complex. sld is a structurally autonomous subunit of the 5' cloverleaf. the sld structure was solved by nmr spectroscopy to an rms deviation of 0.66 a (all heavy atoms). sld contains a novel triple pyrimidine mismatch motif with a central watson-crick type c:u pair. sld is capped by an apical ucacgg tetraloop ...200414962384
alternatively spliced soluble coxsackie-adenovirus receptors inhibit coxsackievirus infection.the coxsackie-adenovirus receptor (car) is a transmembrane receptor of the immunoglobulin superfamily whose expression is altered in myocardial and malignant diseases. soluble isoforms of other adhesion molecules and cytokine receptors have been proven to have significant agonist and antagonist effects on their full-length receptors; however, little is known about soluble car receptors. using reverse transcription-pcr, we identified three car isoforms that lack the transmembrane domain and are t ...200414978041
glutathione depletion and cardiomyocyte apoptosis in viral myocarditis.the course of viral myocarditis is highly variable. oxidative stress and bcl-2 family genes may play a role in its pathogenesis by regulating the amount of cardiomyocyte apoptosis. apoptosis is difficult to detect and quantify in vivo. therefore, we set to look for indicators of this potentially preventable form of cell death during various phases of experimental murine coxsackievirus b3 myocarditis.200415025674
[model of coxsackievirus b3 persistent infection in orally-inoculated balb/c mouse].many mouse models of human enterovirus disease have been pro- posed, concerning both acute and persistent infection. however, rather paradoxically since the usual way of contamination is fecal-oral, most of them used a systemic route of infection. the aim of the present work was to follow the development of an experimental enterovirus infection and to study the viral persistence at the organ level. twenty-eight female 3-week old balb/c mice were infected with 5 x 10(4) tcid(50) of coxsackievirus ...200415047488
protein kinase b/akt regulates coxsackievirus b3 replication through a mechanism which is not caspase dependent.the role of signaling pathways including the mitogen-activated protein kinases (mapks) and phosphatidylinositol 3-kinase (pi3k) during viral infection has gained much recent attention. our laboratory reported on an important regulatory role for extracellular signal-regulated kinases (erk1/2), subfamily members of the mapks, during coxsackievirus b3 (cvb3) infection. however, the role of the pi3k pathway in cvb3 infection has not been well characterized. cvb3 is the most common known viral infect ...200415047842
[a novel dna vaccine containing endosome-fusogenic peptide prevents cvb3-induced myocarditis in mice].to enhance the effect of chitosan-pcdna3-vp1 dna vaccine to prevent onset of coxsackievirus b3 (cvb3)-induced myocarditis.200415059520
coxsackievirus infection of mice. ii. viral kinetics and histopathological changes in mice experimentally infected with coxsackievirus b3 by intraperitoneal route.the study was focused on kinetics of coxsackievirus b3 serotype (cvb3) in different organs of swiss albino mice following intraperitoneal (i.p.) infection. the results indicated that the virus replicated in the heart, spleen, thymus, pancreas, small and large intestines in the acute stage of the infection. infectious virus was present in the spleen till day 35 post infection (p.i.). histopathology of the hearts showed mild foci of infiltration of mononuclear cells in the acute stage of infection ...200315068381
soluble recombinant coxsackievirus and adenovirus receptor abrogates coxsackievirus b3-mediated pancreatitis and myocarditis in mice.group b coxsackievirus infection can result in organ injury and inflammation. the coxsackievirus and adenovirus receptor (car) and decay-accelerating factor (daf; cd55) have both been identified as receptors for coxsackievirus b3 (cvb3). we have shown elsewhere that early daf-fc treatment attenuates cvb3-induced myocarditis and virus replication.200415073680
strand-specific rna synthesis determinants in the rna-dependent rna polymerase of poliovirus.the viral rna-dependent rna polymerase (3d(pol)) is highly conserved between the closely related enteroviruses poliovirus type 1 (pv1) and coxsackievirus b3 (cvb3). in this study, we generated pv1/cvb3 chimeric polymerase sequences in the context of full-length poliovirus transcripts to determine the role of different subdomains within the rna-dependent rna polymerase of pv1 that are required for functions critical for rna replication in vitro and in cell culture. the substitution of cvb3 sequen ...200415078921
a phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus b3 replication in cardiomyocytes and mouse hearts.antisense oligodeoxynucleotides (as-odns) are promising therapeutic agents for the treatment of virus-induced diseases. we previously reported that coxsackievirus b3 (cvb3) infectivity could be inhibited effectively in hela cells by phosphorothioate as-odns complementary to different regions of the 5' and 3' untranslated regions of cvb3 rna. the most effective target is the proximal terminus of the 3' untranslated region. to further investigate the potential antiviral role of the as-odn targetin ...200415094712
increased susceptibility of male balb/c mice to coxsackievirus b3-induced myocarditis: role for cd1d.balb/c male mice infected with the h3 variant of coxsackievirus b3 (cvb3) develop fulminant myocarditis. age-matched female mice show little myocarditis due to decreased virus receptor expression on cardiac cells. tnfalpha and il-1beta levels were increased in males by 3 days after infection. ifngamma levels increased more slowly throughout the 7-day observation period. cd4+, cd8+, macrophage (mac3+) and gammadelta+ cells all accumulated in male hearts, with gammadelta+ cells showing early (day ...200515107990
design, synthesis, and structure-activity relationships of pyrazolo[3,4-d]pyrimidines: a novel class of potent enterovirus inhibitors.a series of pyrazolo[3,4-d]pyrimidines were synthesized and their antiviral activity was evaluated in a plaque reduction assay. it is very interesting that this class of compounds provide remarkable evidence that they are very specific for human enteroviruses, in particular, coxsackieviruses. some derivatives proved to be highly effective in inhibiting enterovirus replication at nanomolar concentrations. sar studies revealed that the phenyl group at the n-1 position and the hydrophobic diarylmet ...200415109643
hemodynamic characterization of left ventricular function in experimental coxsackieviral myocarditis: effects of carvedilol and metoprolol.carvedilol, a vasodilating nonselective beta-adrenoceptor antagonist, but not metoprolol, a selective beta1-adrenoceptor antagonist, has been shown to increase the production of cardiac antiinflammatory cytokines in experimental myocarditis. however, the hemodynamic consequences of these differences had not been investigated until today. therefore, we determined the effects of carvedilol and metoprolol on left ventricular function in a murine model of coxsackievirus b3 (cvb3)-induced myocarditis ...200415140634
immunopathological basis of virus-induced myocarditis.heart diseases are an important cause of morbidity and mortality in industrialized countries. dilated cardiomyopathy (dcm), one of the most common heart diseases, may be the consequence of infection-associated myocardits. coxsackievirus b3 (cvb3) can be frequently detected in the inflamed heart muscle. cvb3-induced acute myocarditis is most likely the consequence of direct virus-induced myocyte damage, whereas chronic cvb3 infection-associated heart disease is dominated by its immunopathological ...200415154605
plasmid-based generation of recombinant coxsackievirus b3 particles carrying capsid gene replacement replicons.recombinant infectious coxsackievirus b3 (cvb3) particles were generated by packaging of modified viral genomes in which the capsid coding p1-region was replaced by an egfp-luciferase reporter gene. efficient packaging of the recombinant genome was achieved by a novel method based on cotransfection of a plasmid encoding the subgenomic viral replicon together with two alternative helper plasmids carrying expression cassettes of the cvb3 capsid proteins, and a t7 rna polymerase expression plasmid. ...200415177888
poliovirus tropism and attenuation are determined after internal ribosome entry.poliovirus replication is limited to a few organs, including the brain and spinal cord. this restricted tropism may be a consequence of organ-specific differences in translation initiation by the poliovirus internal ribosome entry site (ires). a c-to-u mutation at base 472 in the ires of the sabin type 3 poliovirus vaccine strain, known to attenuate neurovirulence, may further restrict tropism by eliminating viral replication in the cns. to determine the relationship between ires-mediated transl ...200415199409
identification of autoantibodies with the corresponding antigen for repetitive coxsackievirus infection-induced cardiomyopathy.the hypothesis that viral myocarditis causes an autoimmune response and subsequent dilated cardiomyopathy is controversial. to further investigate the autoimmune mechanism of cardiac dilatation and dysfunction after repeated episodes of viral myocarditis, the cardiac autoantigens induced by repetitive coxsackievirus b3 (cvb3) infection were examined.200415226635
protective role for interferon-beta in coxsackievirus b3 infection.coxsackievirus-induced myocarditis can be a serious cause of heart failure. in the absence of a specific antiviral therapy, modulating the host immune response may be protective. interferons (ifns)-alpha and -beta perform a fundamental role in innate and adaptive antiviral responses, thereby presenting as candidate therapeutics for coxsackievirus infections.200415249500
mast cells and innate cytokines are associated with susceptibility to autoimmune heart disease following coxsackievirus b3 infection.the development of autoimmune disease involves a combination of genetic and environmental factors. many autoimmune diseases are believed to be triggered by viral infections. since the early, natural immune response to infection can determine the later development of the adaptive immune response, innate immunity likely influences the progression from viral immunity to autoimmunity. to investigate the role of the innate immune response on susceptibility to autoimmune disease, we compared the early ...200415293883
structure determination of coxsackievirus b3 to 3.5 a resolution.the crystal structure of coxsackievirus b3 (cvb3) has been determined to 3.5 a resolution. the icosahedral cvb3 particles crystallize in the monoclinic space group, p2(1), (a = 574.6, b = 302.1, c = 521.6 a, beta = 107.7 degrees ) with two virions in the asymmetric unit giving 120-fold non-crystallographic redundancy. the crystals diffracted to 2.7 a resolution and the x-ray data set was 55% complete to 3.0,4, resolution. systematically weak reflections and the self-rotation function established ...199515299757
intranasal delivery of chitosan-dna vaccine generates mucosal siga and anti-cvb3 protection.coxsackievirus b3 infections are common causes of acute and chronic myocarditis with no effective prophylactic treatment available. we describe here a prophylactic strategy using chitosan-dna intranasal immunization to induce cvb3 specific immune responses. intranasal administration with chitosan-dna complex prepared by votexing dna with chitosan, a natural mucus absorption enhancer, resulted in transgenic dna expression in mouse nasopharynx. mice immunized with chitosan-dna (pcdna3-vp1) encodin ...200415315839
coxsackievirus b3 replication and persistence in intestinal cells from mice infected orally and in the human caco-2 cell line.although the transmission of coxsackievirus b3 occurs mainly via the oral route, little is known about the primary replication and persistence of this agent in the intestine. to address this question, balb/c mice were inoculated by gavage with coxsackievirus b3, nancy strain. the mice were killed from 1 hr to 90 days after infection. the viral markers were detected in the small intestine using rt-pcr, cell culture and detection of vp1 protein. coxsackievirus b3 was detected positive by the three ...200415332278
coxsackie b viruses use multiple receptors to infect human cardiac cells.viral myocarditis is an inflammatory disease of the heart muscle that can be fatal. the primary viruses that have been linked to myocarditis and dilated cardiomyopathy are the human enteroviruses. the most common viruses associated with this disease are the coxsackie b viruses and in particular coxsackievirus b3 and coxsackievirus b5. early events in viral infection include attachment of the virus onto cell surface receptors. even though, cd55 and coxsackievirus adenovirus receptor protein (car) ...200415332279
[antisense oligonucleotide inhibition of coxsackievirus b3 gene expression in hela cells and dose-response experiments].in this study, the authors investigated inhibition of coxsackievirus b (cvb) gene expression using antisense oligonucleotides complementary to the 5' ncr, translation initiation codon and structural protein coding sequences and also observed the dose-response of the sequence specific inhibition of cvb plaque formation by antisense oligonucleotides.200415340530
[myocardial matrix metalloproteinases activities in mice with viral myocarditis and their relationship with cardiac function and myocardial collagen amount].to investigate the dynamic changes of myocardial matrix metalloproteinases (mmps) activities in mice with viral myocarditis (vm) and their relationships with cardiac function and myocardial collagen amount and to explore the role of mmps in the pathologic lesion of vm.200415347449
dynamic changes in myocardial matrix metalloproteinase activity in mice with viral myocarditis.matrix metalloproteinases (mmps) are the major regulators of collagen degradation involved in the pathogenesis of several diseases of the heart. the purpose of this study was to investigate the dynamic changes in myocardial mmp activity in mice with viral myocarditis (vm), the relationship between mmp activity and both cardiac function and the quantity of myocardial collagen, and the role mmps playing in the pathological lesions of vm.200415361294
solution structure of a consensus stem-loop d rna domain that plays important roles in regulating translation and replication in enteroviruses and rhinoviruses.stem-loop d from the cloverleaf rna is a highly conserved domain within the 5'-utr of enteroviruses and rhinoviruses. interaction between the stem-loop d rna and the viral 3c or 3cd proteins constitutes an essential feature of a ribonucleoprotein complex that plays a critical role in regulating viral translation and replication. here we report the solution nmr structure of a 38-nucleotide rna with a sequence that encompasses the entire stem-loop d domain and corresponds to the consensus sequence ...200415379536
antenatal diagnosis of intrauterine infection with coxsackievirus b3 associated with live birth.prior reported cases of stillbirth and neonates infected with enteroviruses suggest transplacental infection. we present a case of fetal infection with coxsackievirus b3, diagnosed antenatally and resulting in live birth.200415460192
coxsackievirus b3 infection and its mutation in keshan disease.to investigate coxsackievirus b(3) infection and its gene mutation in keshan disease.200415484304
co-expression of interleukin-2 to increase the efficacy of dna vaccine-mediated protection in coxsackievirus b3-infected mice.dna immunizations with the major structural protein vp1 of coxsackievirus b3 (cvb3) have been previously found to protect mice from a lethal challenge with cvb3. the function of this vaccination procedure is mainly based on accelerated antibody induction with an early cytokine expression and increased virus-specific cytotoxic activity of spleen cells causing decreased myocyte destruction and reduced viral replication. here, we report that the co-expression of the immune-stimulatory interleukin-2 ...200415498609
coxsackievirus b3 infection and type 1 diabetes development in nod mice: insulitis determines susceptibility of pancreatic islets to virus infection.group b coxsackieviruses (cvb) are believed to trigger some cases of human type 1 diabetes (t1d), although the mechanism by which this may occur has not been shown. we demonstrated previously that inoculation of young nonobese diabetic (nod) mice with any of several different cvb strains reduced t1d incidence. we also observed no evidence of cvb replication within islets of young nod mice, suggesting no role for cvb in t1d induction in the nod mouse model. the failure to observe cvb replication ...200415518817
myocarditis susceptibility in female mice depends upon ovarian cycle phase at infection.female balb/c mice were infected with coxsackievirus b3 in the diestrus, proestrus, estrus, or metestrus phases of the ovarian cycle. cycle stage was determined by vaginal smear. all mice were killed 7 days after infection. females infected in the diestrus and especially the proestrus phases developed myocarditis. cd4+ t cells expressing interferon-gamma (ifngamma) infiltrate the myocardium in these two phases, whereas cd4+ t cells expressing il-4 are more frequent during estrus. cardiac virus t ...200415527830
generation and analysis of an rna vaccine that protects against coxsackievirus b3 challenge.coxsackievirus b3 (cvb3) is an important human pathogen that causes substantial morbidity and mortality but, to date, no vaccine is available. we have generated an rna-based vaccine against cvb3 and have evaluated it in the murine model of infection. the vaccine was designed to allow production of the viral polyprotein, which should be cleaved to generate most of the viral proteins in their mature form; but infectious virus should not be produced. in vitro translation studies indicated that the ...200415527846
differential rescue of poliovirus rna replication functions by genetically modified rna polymerase precursors.we have previously described the rna replication properties of poliovirus transcripts harboring chimeric rna polymerase sequences representing suballelic exchanges between poliovirus type 1 (pv1) and coxsackievirus b3 (cvb3) utilizing an in vitro translation and rna replication assay (c. cornell, r. perera, j. e. brunner, and b. l. semler, j. virol. 78:4397-4407, 2004). we showed that three of the seven chimeras were capable of rna replication in vitro, although replication levels were greatly r ...200415542652
women and autoimmune diseases.autoimmune diseases affect approximately 8% of the population, 78% of whom are women. the reasons for the high prevalence in women are unknown, but circumstantial evidence links autoimmune diseases with preceding infections. animal models of autoimmune diseases have shown that infections can induce autoimmune disease. for example, coxsackievirus b3 (cb3) infection of susceptible mice results in inflammation of the heart (myocarditis) that resembles myocarditis in humans. the same disease can be ...200415550215
late constrictive involvement of the pericardium in a case of previous myocarditis.constrictive pericarditis (cp) is a highly relevant disease clinically because pericardiectomy represents the only curative therapeutic approach. previous cardiac surgery or mediastinal radiation may cause cp, however, infectious agents account for a substantial portion of cp. in this report, we present a patient with previous biopsy-proven myocarditis and positive seroconversion against coxsackievirus b3 without clinical evidence of acute pericardial involvement who developed cp after a prolong ...200415556780
coxsackievirus b3 infection induces cyr61 activation via jnk to mediate cell death.coxsackievirus b3 (cvb3), an enterovirus in the picornavirus family, is the most common human pathogen associated with myocarditis and idiopathic dilated cardiomyopathy. we found upregulation of the cysteine-rich protein gene (cyr61) after cvb3 infection in hela cells with a cdna microarray approach, which is confirmed by northern blot analysis. it is also revealed that the extracellular amount of cyr61 protein was increased after cvb3 infection in hela cells. cyr61 is an early-transcribed gene, ...200415564459
attenuating mutations in coxsackievirus b3 map to a conformational epitope that comprises the puff region of vp2 and the knob of vp3.ten antibody escape mutants of coxsackievirus b3 (cvb3) were used to identify nucleotide substitutions that determine viral virulence for the heart and pancreas. the p1 region, encoding the structural genes of each mutant, was sequenced to identify mutations associated with the lack of neutralization. eight mutants were found to have a lysine-to arginine mutation in the puff region of vp2, while two had a glutamate-to-glycine substitution in the knob of vp3. two mutants, em1 and em10, representi ...200415564506
plasma concentrations of cytokines and neurohumoral factors in a case of fulminant myocarditis successfully treated with intravenous immunoglobulin and percutaneous cardiopulmonary support.a 53-year-old japanese man with fulminant myocarditis was referred. percutaneous cardiopulmonary support (pcps) was introduced immediately and intravenous immunoglobulin (ivig) therapy followed for 2 days. cardiac function showed signs of recovery on the 4th hospital day and the patient was weaned from pcps on the 7th hospital day. creatine kinase-mb peaked at 12 h after admission and was 176 ng/ml. endomyocardial biopsy showed active myocarditis. a marked increase of the neutralizing antibody t ...200415564712
detection of coxsackievirus b3 rna in mouse myocarditis by nested polymerase chain reaction.a majority of cases of viral myocarditis are associated with group b coxsackieviruses (cvb) and the persistence of these viruses in the myocardium is associated with the progression of acute myocarditis to chronic dilated cardiomyopathy. a highly sensitive nested polymerase chain reaction (npcr) is required to study the mechanisms of viral persistence in the myocardium.199515566805
anti-coxsackievirus b3 activity of 2-amino-3-nitropyrazolo[1,5-a]pyrimidines and their analogs.a novel class of 2-amino-4-nitropyrazolo[1,5-a]pyrimidines has been identified as potent inhibitors of coxsackievirus b3 replication. the synthesis of these compounds is based on the regioselective reaction of 3,5-diamino-5-nitropyrazole with unsymmetrical beta-diketones at catalysis by hydrochloric acid leading to 2-amino-4-nitropyrazolo[1,5-a]pyrimidines as key steps.200515582406
benign coxsackievirus damages heart muscle in iron-loaded vitamin e-deficient mice.several oxidative stressors (dietary selenium deficiency, dietary vitamin e deficiency coupled with fish oil feeding, genetic reduction of glutathione peroxidase activity) allow a normally benign coxsackievirus b3 (cvb3/0) to damage heart muscle in host mice. this study investigated whether dietary iron overload, another oxidant stress, would also permit cvb3/0 to exert a cardiopathologic effect in vitamin e-deficient (-ve) mice. four groups of mice were fed either a -ve or a +ve diet containing ...200515589379
interaction with coxsackievirus and adenovirus receptor, but not with decay-accelerating factor (daf), induces a-particle formation in a daf-binding coxsackievirus b3 isolate.although many coxsackie b viruses interact with decay accelerating factor (daf), attachment to daf by itself is not sufficient to initiate infection. we examined the early events in infection that follow virus interaction with daf, and with the coxsackievirus and adenovirus receptor (car). interaction with soluble car in a cell-free system, or with car on the surfaces of transfected cells, induced the formation of a particles; interaction with soluble or cell surface daf did not. the results sug ...200515596863
[anti-enterovirus and immunostimulating activity of the polyphenol complex extracted from pethaphylloides fruticosa (l.) o. schwarz].studied within the present case study was the antiviral and viricidal activity of the water-soluble polyphenol complex, obtained from penthaphylloides fruticosa (l.) o. schwarz, in respect to enteroviruses coxsackie b. the complex had a low toxicity and high chemotherapeutic index when introduced experimentally in the cell culture. the therapeutic effect of the water-soluble extract was detected in an experimental infection of newborn mice caused by coxsackievirus b3. the interferongenic and imm ...200415597958
all cvb serotypes and clinical isolates induce irreversible cytopathic effects in primary cardiomyocytes.coxsackievirus b3 (cvb3) has been identified as a major causative agent of acute and chronic myocarditis, but the involvement of other cvb serotypes in myocarditis has not been investigated. to dissect the pathological properties of different cvb serotypes toward primary cardiomyocytes, we tested their effects on primary cardiomyocyte cultures from neonatal rats. morphological abnormalities were examined by both light and fluorescence microscopy after hoechst 33342 staining, and loss of cell via ...200515602738
characterization of an infectious cdna copy of the genome of a naturally occurring, avirulent coxsackievirus b3 clinical isolate.group b coxsackieviruses (cvb) cause numerous diseases, including myocarditis, pancreatitis, aseptic meningitis and possibly type 1 diabetes. to date, infectious cdna copies of cvb type 3 (cvb3) genomes have all been derived from pathogenic virus strains. an infectious cdna copy of the well-characterized, non-pathogenic cvb3 strain ga genome was cloned in order to facilitate mapping of the cvb genes that influence expression of a virulence phenotype. comparison of the sequence of the parental cv ...200515604447
il-12 protects against coxsackievirus b3-induced myocarditis by increasing ifn-gamma and macrophage and neutrophil populations in the heart.th1-type immune responses, mediated by il-12-induced ifn-gamma, are believed to exacerbate certain autoimmune diseases. we recently found that signaling via il-12rbeta1 increases coxsackievirus b3 (cvb3)-induced myocarditis. in this study, we examined the role of il-12 on the development of cvb3-induced myocarditis using mice deficient in il-12p35 that lack il-12p70. we found that il-12 deficiency did not prevent myocarditis, but viral replication was significantly increased. although there were ...200515611248
analysis of translational initiation in coxsackievirus b3 suggests an alternative explanation for the high frequency of r+4 in the eukaryotic consensus motif.translational initiation of most eukaryotic mrnas occurs when a preinitiation complex binds to the 5' cap, scans the mrna, and selects a particular aug codon as the initiation site. selection of the correct initiation codon relies, in part, on its flanking residues; in mammalian cells, the core of the "kozak" consensus is r-3ccaugg+4 (r=purine; the a residue is designated position +1). the r-3 is considered the most important flanking residue, followed by g+4. picornaviral mrnas differ from most ...200515613327
[experimental comparison of two coxsackievirus b3 variants in murine myocardial cells].there is lack of direct evidence whether the myocarditis can be induced by cvb3o. the two coxsackievirus b3 variants were used to infected murine myocardial cells. the results showed that: (1) in culture medium of murine myocardial cells infected with two variants, it did not show much differences in titers at 12 and 24 hours between cvb3o and cvb3m. (2) the two variants could all induce the death of myocardium, but with the elapse of time, the cell death rate of cvb3m infected cells was much hi ...199715617347
[coxsackievirus b3-induction of tumor necrosis factor and il-6 of murine monocyte-macrophages].this study is to observe the infection of coxsackievirus b3 (cox b3) to murine monocyte-macrophages (mo/mpsi), and its induction of tumor necrosis factor (tnf) and il-6. cox b3 was capable of infecting murine macrophages as revealed by immunofluorescence and releasing infectious virus particles. virus infection with < or = 100 tcid50 did not reduce macrophages viability. cox b3 stimulated the release of monokines from mo/mpsi in vitro and in vivo, markedly increasing the concentration of tnf and ...199715619829
maintaining inhibition: sirna double expression vectors against coxsackieviral rnas.the potential of rna interference (rnai) to inhibit virus propagation has been well established in recent years. in several studies, however, emergence of viral escape mutants after prolonged exposure to rnai has been observed, raising a major hurdle for a possible therapeutic application of this strategy. here, we report the design and characterisation of a vector that allows the simultaneous expression of two short hairpin rnas (shrnas), thereby maintaining high silencing activity even against ...200415670596
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