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estimation of seroprevalence of encephalomyocarditis in dutch sow herds using the virus neutralization test.encephalomyocarditis virus (emcv) has been found on pig farms worldwide and can cause myocarditis in young pigs and reproduction disorders in sows. so far, clinical signs of emcv have not been reported in the netherlands. the aim of this study was to estimate the seroprevalence of emcv infection in dutch sow herds. a total of 277 dutch sow herds were randomly selected, from which 3237 serum samples were collected. these samples were tested for emcv antibodies using the virus neutralization test ...200616454087
characterization of a novel bioflocculant, p-kg03, from a marine dinoflagellate, gyrodinium impudicum kg03.the flocculating activity of an exopolysaccharide, p-kg03, produced by a marine dinoflagellate gyrodinium impudicum kg03 was investigated. the p-kg03 was a highly sulfated exopolysaccharide that showed strong antiviral activity against encephalomyocarditis virus (emcv) and immunostimulating activity by nk cell activation. for the industrial applications of p-kg03, as the bioflocculant agent, p-kg03 showed that more than 90% of the flocculating activity in kaolin suspension occurred at concentrat ...200716473007
impaired expression of cardiac adiponectin in leptin-deficient mice with viral myocarditis.a mouse model of encephalomyocarditis (emc) virus-induced myocarditis was used to investigate the expression of adiponectin in damaged cardiomyocytes. we intraperitoneally injected emc virus into leptin-deficient ob/ob (ob) mice and wild-type (wt) mice. ob mice were divided into two subgroups consisting of mice with no intervention and mice receiving leptin replacement starting simultaneously with viral inoculation. we determined differences in heart weight, cardiac histological score, numbers o ...200616479046
[expression of interferon alpha family gene of chinese marmot in eukaryotic and prokaryotic cells].to investigate the function of interferon alpha (ifnalpha) in a chinese marmot model of hepatitis b, we expressed the chinese marmot (marmota himalayana) ifnalpha family gene (ifna) in eukaryotic cells and prokaryotic cells.200616494783
nucleocytoplasmic traffic disorder induced by cardioviruses.some picornaviruses, for example, poliovirus, increase bidirectional permeability of the nuclear envelope and suppress active nucleocytoplasmic transport. these activities require the viral protease 2a(pro). here, we studied nucleocytoplasmic traffic in cells infected with encephalomyocarditis virus (emcv; a cardiovirus), which lacks the poliovirus 2a(pro)-related protein. emcv similarly enhanced bidirectional nucleocytoplasmic traffic. by using the fluorescent "timer" protein, which contains a ...200616501080
destruction of human retinoblastoma after treatment by the e variant of encephalomyocarditis virus.the oncolytic effects of encephalomyocarditis (emc) virus were examined in human retinoblastoma cell (y79) cultures which were infected with 10(4 )tissue culture infectious doses (tcids) of the e variant of emc (emc-e) virus. the tcids were used to titer the maximum effect of emc virus on l-929 cells. in-vitro studies showed 90% cytopathic effect (cpe) at 24 h and 100% cpe at 52 h. the cpe was used to observe pathologic effects of the cells. in-vivo studies employing human retinoblastoma grown a ...200616528457
multicistronic lentiviral vectors containing the fmdv 2a cleavage factor demonstrate robust expression of encoded genes at limiting moi.a number of gene therapy applications would benefit from vectors capable of expressing multiple genes. in this study we explored the feasibility and efficiency of expressing two or three transgenes in hiv-1 based lentiviral vector. bicistronic and tricistronic self-inactivating lentiviral vectors were constructed employing the internal ribosomal entry site (ires) sequence of encephalomyocarditis virus (emcv) and/or foot-and-mouth disease virus (fmdv) cleavage factor 2a. we employed enhanced gree ...200616539700
protection of mice against bacterial infection by interferon inducers.antibacterial effect of known interferon inducers was investigated. intraperitoneal injection of statolon or pyran markedly enhanced the survival of mice challenged with klebsiella pneumoniae. the sparing effect of these two interferon inducers resembled that of bacterial endotoxin. significant protection was obtained when the inducers were administered 24 hr before challenge. treatments given 6 hr before or at the time of infection were ineffective. the persistence of increased resistance of tr ...197016557727
interferon synthesis in x-irradiated animals v. origin of mouse serum interferon induced by polyinosinic-polycytidylic acid and encephalomyocarditis virus.the radioresistant cell systems producing serum interferon after intravenous administration of polyinosinic-polycytidylic acid [poly(i.c)] or encephalomyocarditis virus in mice were studied in rat-to-mouse radiation chimeras. interferon induced by poly(i.c) became of donor type within 3 months after grafting of irradiated c3h/he mice with wistar rat bone marrow cells; this indicated that it was made in cells derived from the hemopoietic system. in contrast, encephalomyocarditis virus-induced int ...197416558083
characterization of a recombinant encephalomyocarditis virus expressing the enhanced green fluorescent protein.a recombinant encephalomyocarditis virus (remcv2887a-egfp) expressing the enhanced green fluorescent protein (egfp) was produced. the egfp gene was inserted in frame within the leader protein coding sequence of a full-length cdna clone of emcv. rna transcripts derived from the recombinant full-length cdna were synthesized in vitro and transfected into bhk-21 cells. the recombinant transcript rna remained infectious despite the insertion of egfp as shown by cytopathic effects on bhk-21 cells and ...200616575480
cardiovirus leader proteins are functionally interchangeable and have evolved to adapt to virus replication fitness.the leader (l) proteins encoded by picornaviruses of the genus cardiovirus [theiler's murine encephalomyelitis virus (tmev) and encephalomyocarditis virus (emcv)] are small proteins thought to exert important functions in virus-host interactions. the l protein of persistent tmev strains was shown to be dispensable for virus replication in vitro, but crucial for long-term persistence of the virus in the central nervous system of the mouse. the phenotype of chimeric viruses generated by exchanging ...200616603526
lambda interferon (ifn-lambda), a type iii ifn, is induced by viruses and ifns and displays potent antiviral activity against select virus infections in vivo.type iii interferons (ifns) (interleukin-28/29 or lambda interferon [ifn-lambda]) are cytokines with ifn-like activities. here we show that several classes of viruses induce expression of ifn-lambda1 and -lambda2/3 in similar patterns. the ifn-lambdas were-unlike alpha/beta interferon (ifn-alpha/beta)-induced directly by stimulation with ifn-alpha or -lambda, thus identifying type iii ifns as ifn-stimulated genes. in vitro assays revealed that ifn-lambdas have appreciable antiviral activity agai ...200616611910
differential roles of mda5 and rig-i helicases in the recognition of rna viruses.the innate immune system senses viral infection by recognizing a variety of viral components (including double-stranded (ds)rna) and triggers antiviral responses. the cytoplasmic helicase proteins rig-i (retinoic-acid-inducible protein i, also known as ddx58) and mda5 (melanoma-differentiation-associated gene 5, also known as ifih1 or helicard) have been implicated in viral dsrna recognition. in vitro studies suggest that both rig-i and mda5 detect rna viruses and polyinosine-polycytidylic acid ...200616625202
lentiviral vectors harboring a dual-gene system allow high and homogeneous transgene expression in selected polyclonal human embryonic stem cells.genetic modification of human embryonic stem cells (hescs) is highly valuable for their exploitation in basic science and therapeutic applications. here we developed lentiviral vectors (lvs) constitutively expressing a reporter and a selectable marker to enable high and homogeneous transgene expression within polyclonal hescs. lvs carrying gfp and a downstream puromycin resistance gene, linked by the encephalomyocarditis virus (emcv) or poliovirus internal ribosome entry sites (ires), allowed ho ...200616632408
integrin alpha 11 is a novel type i interferon stimulated gene.interferons (ifns) are a family of cytokines that have many biological functions in the cell, including regulation of cellular growth, differentiation, immunomodulation, and viral replication by inducing a set of interferon stimulated genes (isgs). based on their structure and biological activities ifns are subdivided into two groups: type i ifns, which includes ifn-alpha and ifn-beta and type ii ifns, represented by ifn-gamma. the aim of this work was to investigate whether integrin alpha 11 (i ...200616697656
relevance of inflammatory cell infiltrates for complete atrioventricular block in experimental murine myocarditis.there are few systemic pathologic studies on myocarditis. this study aimed to clarify the pathologic characteristics of murine myocarditis.200616697926
essential role of mda-5 in type i ifn responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus.the innate immune system recognizes viral dsrna through two distinct pathways; the toll-like receptor 3 (tlr3) pathway detects dsrna phagocytosed in endosomes; the helicases retinoic acid-induced protein i (rig-i) and melanoma differentiation-associated gene-5 (mda-5) detect cytoplasmic dsrna generated during viral replication. both rig-i and mda-5 can bind polyriboinosinic:polyribocytidylic acid (polyi:c), the synthetic analog of viral dsrna, and mediate type i ifn responses to polyi:c and mult ...200616714379
successful implantation of intravenously administered stem cells correlates with severity of inflammation in murine myocarditis.the present study was designed to determine whether cardiac inflammation is important for the successful homing of stem cells to the heart after intravenous injection in a murine myocarditis model. male bagg albino/c mice were infected with encephalomyocarditis virus (emcv) to produce myocarditis. subgroups of mice received single injections by tail vein of embryonic stem cells (escs) transfected with green fluorescent protein (gfp) as a marker at days 3, 14, or 60 after infection; other subgrou ...200616715295
blocking of interferon-induced jak-stat signaling by japanese encephalitis virus ns5 through a protein tyrosine phosphatase-mediated mechanism.japanese encephalitis virus (jev), a mosquito-borne flavivirus that causes severe human disease, has been shown to block the interferon (ifn)-induced janus kinase signal transducer and activation of transcription (jak-stat) signaling cascade by preventing tyk2 tyrosine phosphorylation and stat activation. in this study, we demonstrate that expression of the jev nonstructural protein ns5 readily blocked ifn-stimulated jak-stat signaling events such as stat1 nuclear translocation and tyrosine phos ...200616731929
inhibition of protein synthesis in cell-free systems from interferon-treated, infected cells: further characterization and effect of formylmethionyl-trna(f).the translation of encephalomyocarditis virus (emc) rna is markedly inhibited in cell-free systems from interferon-treated, vaccinia virus-infected l-cells (10, 11). the polypeptide products synthesized in response to emc rna in cell-free systems from these and untreated infected cells have been analyzed by electrophoresis on polyacrylamide gels. qualitatively, the same emc-specific polypeptides were synthesized throughout. in experiments using preincubated microsomes from normal krebs cells to ...197416789138
internal ribosome entry sequence-mediated translation initiation triggers nonsense-mediated decay.in eukaryotes, a surveillance pathway known as nonsense-mediated decay (nmd) regulates the abundance of messenger rnas containing premature termination codons (ptcs). in mammalian cells, it has been asserted that the nmd-relevant first round of translation is special and involves initiation by a specific protein heterodimer, the nuclear cap-binding complex (cbc). arguing against a requirement for cbc-mediated translation initiation, we show that ribosomal recruitment by the internal ribosomal en ...200616799467
cd1d mediates t-cell-dependent resistance to secondary infection with encephalomyocarditis virus (emcv) in vitro and immune response to emcv infection in vivo.the innate and adaptive immune responses have evolved distinct strategies for controlling different viral pathogens. encephalomyocarditis virus (emcv) is a picornavirus that can cause paralysis, diabetes, and myocarditis within days of infection. the optimal innate immune response against emcv in vivo requires cd1d. interaction of antigen-presenting cell cd1d with distinct natural killer t-cell ("nkt") populations can induce rapid gamma interferon (ifn-gamma) production and nk-cell activation. t ...200616809320
the gamma interferon (ifn-gamma) mimetic peptide ifn-gamma (95-133) prevents encephalomyocarditis virus infection both in tissue culture and in mice.we have demonstrated previously that the c-terminal gamma interferon (ifn-gamma) mimetic peptide consisting of residues 95 to 133 [ifn-gamma(95-133)], which contains the crucial ifn-gamma nuclear localization sequence (nls), has antiviral activity in tissue culture. here we evaluate the efficacy of this peptide and its derivatives first in vitro and then in an animal model of lethal viral infection with the encephalomyocarditis (emc) virus. deletion of the nls region from the ifn-gamma mimetic p ...200616893996
role of mapk in the regulation of double-stranded rna- and encephalomyocarditis virus-induced cyclooxygenase-2 expression by macrophages.in response to virus infection or treatment with dsrna, macrophages express the inducible form of cyclooxygenase-2 (cox-2) and produce proinflammatory prostaglandins. recently, we have shown that nf-kappab is required for encephalomyocarditis virus (emcv)- and dsrna-stimulated cox-2 expression in mouse macrophages. the dsrna-dependent protein kinase r is not required for emcv-stimulated cox-2 expression, suggesting the presence of protein kinase r-independent pathways in the regulation of this a ...200616920983
ionic contra-viral therapy (icvt); a new approach to the treatment of dna virus infections.the sequestration of cellular k(+) has been shown elsewhere to elicit a broad spectrum of antiviral activity. the obligatory, coupled cotransports of na(+), k(+) and cl(-) (nkcc1) and of na(+) and k(+) (nkatpase) effect net cellular k(+) influx. we examined the effects of specific inhibitors of these transports; a cardiac glycoside (digoxin) and a loop diuretic (furosemide) on virus replication in vitro. the replication of the dna viruses, herpes simplex virus, varicella zoster virus, human cyto ...200616932984
toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury.enterovirus-induced myocardial injury can lead to severe heart failure. to date, little is known about the early innate stress response that contributes to host defense in the heart. toll-like receptor 3 (tlr3) is important in the initiation of the innate antiviral response. we investigated the involvement of tlr3, which recognizes viral double-stranded rna, on encephalomyocarditis virus (emcv) infection. to examine the contribution of tlr3 in protection from emcv infection, we infected mice def ...200716936008
pathogenesis of experimental encephalomyocarditis: a histopathological, immunohistochemical and virological study in mice.mice (n=20) aged 8 weeks were infected, either by oronasal inoculation or by contact, with one of two different myocardial strains of encephalomyocarditis virus (emcv), namely, the greek strain 424/90 and the belgian strain b279/95. the animals were killed at 18-59 days post-infection (dpi), except for two mice that died at 6 and 32 dpi, and samples of brain, heart, pancreas, kidney, peyer's patches, spleen, lung and thymus were processed for virological, histopathological and immunohistochemica ...200616952370
differential cleavage of eif4gi and eif4gii in mammalian cells. effects on translation.two isoforms of the translation initiation factor eif4g, eif4gi and eif4gii, have been described in eukaryotic cells. the exact function of each isoform during the initiation of protein synthesis is still under investigation. we have developed an efficient and reliable method of expressing poliovirus 2apro, which differentially proteolyzes eif4gi and eif4gii in a time- and dose-dependent manner. this system is based on the electroporation of an in vitro transcribed mrna that contains the encepha ...200616959778
transmission of encephalomyocarditis virus in pigs estimated from field data in belgium by means of r0.transmission of encephalomyocarditis-virus (emcv) has been estimated in experiments, but never using field data. in this field study, a farm in belgium was selected where the presence of emcv was confirmed by necropsy and virus isolation. serology was used to estimate the transmission parameter r0. in one compartment with 630 pigs, 6 pens were fully sampled, in the remaining 38 pens, 2 randomly selected pigs were bled. the 151 pigs were bled twice and their serum was tested in a virus neutralisa ...200616973116
translational efficiency of emcv ires in bicistronic vectors is dependent upon ires sequence and gene location.the internal ribosomal entry site (ires)from encephalomyocarditis virus (emcv) is a popular rna element used widely in experimental and pharmaceutical applications to express proteins in eukaryotic cells or cell-free extracts. inclusion of the wild-type element in monocistronic or bicistronic messenger rnas (mrnas) confers a high level of cap-independent translation activity to appropriately configured cistrons. the history of this element and the experimental consequences of sequence derivation ...200616989088
production of biopharmaceuticals and vaccines in plants via the chloroplast genome.transgenic plants offer many advantages, including low cost of production (by elimination of fermenters), storage and transportation; heat stability; and absence of human pathogens. when therapeutic proteins are orally delivered, plant cells protect antigens in the stomach through bioencapsulation and eliminate the need for expensive purification and sterile injections, in addition to development of both systemic and mucosal immunity. chloroplast genetic engineering offers several advantages, in ...200617004305
effects of picornavirus 3a proteins on protein transport and gbf1-dependent cop-i recruitment.the 3a protein of the coxsackievirus b3 (cvb3), an enterovirus that belongs to the family of the picornaviruses, inhibits endoplasmic reticulum-to-golgi transport. recently, we elucidated the underlying mechanism by showing that cvb3 3a interferes with adp-ribosylation factor 1 (arf1)-dependent cop-i recruitment to membranes by binding and inhibiting the function of gbf1, a guanine nucleotide exchange factor that is required for the activation of arf1 (e. wessels et al., dev. cell 11:191-201, 20 ...200617005635
rig-i-mediated antiviral responses to single-stranded rna bearing 5'-phosphates.double-stranded rna (dsrna) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the rna helicase enzymes retinoic acid-inducible gene i (rig-i) and melanoma differentiation-associated gene 5 (mda5). we showed that influenza a virus infection does not generate dsrna and that rig-i is activated by viral genomic single-stranded rna (ssrna) bearing 5'-phosphates. this is blocked by the influenza protein nonstructured protein 1 (ns ...200617038589
serological survey of encephalomyocarditis virus infection in pigs in france.samples of serum from 76 gilts, 1440 sows, 1473 piglets and 3093 finishing pigs from 96 farrow-to-finish herds were tested for antibodies to encephalomyocarditis virus (emcv) in microtitre serum neutralisation tests employing two strains of virus, one associated with myocarditis and the other with reproductive failure. the total seroprevalence of emcv infection was 2.48 per cent. there was no significant difference between the seroprevalence of the reproductive failure strain (1.6 per cent) and ...200617041064
design, synthesis, and biological evaluation of novel iso-d-2',3'-dideoxy-3'-fluorothianucleoside derivatives.novel iso-d-2',3'-dideoxythianucleoside derivatives 1-4 were designed and asymmetrically synthesized as a bioisostere of lamivudine to search for new anti-hiv agents. the information about using sulfur participation occurred on dast fluorination and mitsunobu reaction will be of great help in synthesizing sulfur-containing compounds. final compounds 1-4 were evaluated against hiv-1 and 2, hsv-1 and 2, emcv, cox. b3, vsv, flua (taiwan), flua (johan.), fcv, and fip. only cytosine analogue 3 showed ...200717046264
the degree of apoptosis as an immunostimulant for a dna vaccine against hiv-1 infection.to regulate the expression of the apoptotic gene, we constructed bicistronic dna vaccines that encode for hiv env and caspase-3 mutant (casp 3m) that are expressed via the encephalomyocarditis virus internal ribosomal entry site (ires) or cytomegalovirus (cmv) promoter-dependent translations. while ires-casp 3m induced weak apoptosis and caused little reduction in antigen expression, cmv-casp 3m elicited strong apoptosis and led to a marked decrease in the antigen expression. therefore, ires-cas ...200717079059
factors related to the incidence of clinical encephalomyocarditis virus (emcv) infection on belgian pig farms.we set up a matched case-control study of potential risk factors for clinical encephalomyocarditis virus (emcv) in 58 pig farms in west flanders (belgium). in total, 29 farms experienced a clinical outbreak of emcv confirmed by emc virus isolation. mortality was seen only among suckling piglets (18 case farms), in piglets and other age-groups (4 case farms), or only among fattening pigs (7 case farms). five farms had reproductive problems among the sows. control farms were matched geographically ...200717098310
viral infections as potential triggers of type 1 diabetes.during the last decades, the incidence of type 1 diabetes (t1d) has increased significantly, reaching percentages of 3% annually worldwide. this increase suggests that besides genetical factors environmental perturbations (including viral infections) are also involved in the pathogenesis of t1d. t1d has been associated with viral infections including enteroviruses, rubella, mumps, rotavirus, parvovirus and cytomegalovirus (cmv). although correlations between clinical presentation with t1d and th ...200717103489
helper virus-independent trans-replication of hepatitis c virus-derived minigenome.we have previously described a synthetic t7-driven cdna minigenome containing the antisense sequence of luciferase gene and internal ribosome entry site of encephalomyocarditis virus flanked by 5'- and 3'-end sequences of hepatitis c virus (hcv) that contain cis-acting replication elements. synthesis of minus-strand rna from the artificial minigenome was determined by using huh-7 cells harboring autonomously replicating hcv subgenome as a helper for provision of functional replication components ...200717112469
neutralizing antibodies to interferon beta in multiple sclerosis: analytical evaluation for validation of a cytopathic effect assay.recent guidelines have recommended the use of validated assays for the measurement of neutralizing antibodies (nabs) to interferon beta (ifnbeta) in patients with multiple sclerosis (ms). in an attempt of validation, we studied the analytical performance of a bioassay based on antiviral cytopathic effect (cpe) using wish cells and the vesicular stomatitis virus (wish/vsv cpe).200717123498
viruses cause type 1 diabetes in animals.more than 10 viruses have been reported to be associated with the development of type 1 diabetes-like symptoms in animals, with the best evidence coming from studies on the d variant of encephalomyocarditis (emc-d) virus in mice and kilham rat virus (krv) in rats. a high titer of emc-d viral infection results in the development of diabetes within 3 days, primarily due to the rapid destruction of beta cells by viral replication within the cells. a low titer of emc-d viral infection results in the ...200617130545
degradation of the encephalomyocarditis virus and hepatitis a virus 3c proteases by the ubiquitin/26s proteasome system in vivo.we have isolated stably transfected mouse embryonic fibroblast cell lines that inducibly express either the mature encephalomyocarditis virus (emcv) or hepatitis a virus (hav) 3c protease and have used these cells to demonstrate that both proteins are subject to degradation in vivo by the ubiquitin/26s proteasome system. the detection of 3c protease expression in these cells requires inducing conditions and the presence of one of several proteasome inhibitors. both 3c proteases are incorporated ...200717150238
a comparative study of different vector designs for the mammalian expression of recombinant igg antibodies.monoclonal antibodies (mab) are the fastest growing group of biopharmaceuticals in development. for production in mammalian cells, the four polypeptide chains of the immunoglobulin diheterotetramer must be assembled prior to exit from the endoplasmic reticulum. various recombinant mab expression vectors have been developed utilizing mono-and bicistronic expression cassettes encoded on one or two plasmids. however, there are only few studies providing information on the type of vector design opti ...200717161420
qualitative and quantitative analysis of antibody response against ifnbeta in patients with multiple sclerosis.to date, inter- and intra-laboratory consistency of binding assays for measuring anti-interferon (ifn)beta antibodies has not been assessed. in this investigation, two independent laboratories tested a library of 80 serum specimens obtained from multiple sclerosis (ms) patients treated with ifnbeta. for binding antibodies (babs) evaluations, each laboratory used both a capture-elisa (celisa) and an enzyme-immuno-assay (eia), which is commercially available. samples were also tested for neutraliz ...200617263001
raman and raman optical activity (roa) analysis of rna structural motifs in domain i of the emcv ires.raman and raman optical activity (roa) spectra were collected for four rna oligonucleotides based on the emcv ires domain i to assess the contributions of helix, gnra tetraloop, u.c mismatch base pair and pyrimidine-rich bulge structures to each. both raman and roa spectra show overall similarities for all oligonucleotides, reflecting the presence of the same base paired helical regions and gnra tetraloop in each. specific bands are sensitive to the effect of the mismatch and asymmetric bulge on ...200717264119
genetic redundancy in human cervical carcinoma cells: identification of cells with "normal" properties.although it is generally assumed that cancer arises from a singular cell, a tumor must be considered as a dynamic and emergent biological structure, whose organizing principle is determined by genetic and epigenetic modifications, occurring variably in response to microenvironmental selection conditions. as previously shown, hpv-positive cervical carcinoma cells have lost their ability to induce ifn-beta upon tnf-alpha treatment. however, regarding cancer as a non-linear system, which may, even ...200717266037
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
reduced-energy diet improves survival of obese kkay mice with viral myocarditis: induction of cardiac adiponectin expression.obesity is an important risk factor for heart disease. whether weight loss affects the severity of heart failure induced by viral myocarditis is a matter of debate. we hypothesized that weight loss could improve cardiac dysfunction by inducing cardiac expression of a cardioprotective cytokine, adiponectin. we examined the relationship between weight loss by food restriction and heart failure due to viral myocarditis in obese kkay mice. we intraperitoneally injected encephalomyocarditis virus (50 ...200717275107
non-suppurative meningoencephalitis of unknown origin in cats and dogs: an immunohistochemical study.non-suppurative meningoencephalitis of unknown cause is a frequent finding in dogs and cats. fifty-three dogs and 33 cats with non-suppurative meningoencephalitis of unknown aetiology were examined immunohistochemically for 18 different infectious agents, including viruses, bacteria and prion protein(sc). in 14 (26%) of the dogs and 13 (39%) of the cats a causative agent was identified in the central nervous system (cns), two dogs and one cat giving positive results for two infectious agents sim ...200717275833
genomic analysis of two porcine encephalomyocarditis virus strains isolated in china.two strains of encephalomyocarditis virus (emcv), designated bjc3 and hb1, were isolated from an aborted fetus and the heart tissue of a dead piglet that had pericardial fluid, respectively. the complete genomic sequences of the two viruses were determined and analyzed. the size of the genomes of bjc3 and hb1 were 7746 and 7735 nucleotides, respectively, including poly(a) tails. comparative analysis with the genomic sequences of other emcv strains showed that bjc3 and hb1 shared higher identity ...200717294091
serologic responses of barbary sheep (ammotragus lervia), indian antelope (antilope cervicapra), wallaroos (macropus robustus), and chimpanzees (pan troglodytes) to an inactivated encephalomyocarditis virus vaccine.encephalomyocarditis virus (emcv) is a picornavirus with a worldwide distribution, capable of infecting a wide range of species. episodes of emcv-associated mortality have been reported in zoos and national parks around the world, including sporadic cases at taronga zoo, sydney. an inactivated emcv vaccine was evaluated by inoculating barbary sheep (ammotragus lervia), indian antelope (antilope cervicapra), eastern wallaroos (macropus robustus), and chimpanzees (pan troglodytes). a proportion of ...200517315459
an improved cell-free system for picornavirus synthesis.cell-free synthesis of an infectious virus is an ideal tool for elucidating the mechanism of viral replication and for screening anti-viral drugs. in the present study, the synthesis of encephalomyocarditis virus (emcv) from its rna in hela and 293-f cell extracts was enhanced by employing a dialysis system in combination with a ribozyme technology. although translation and processing of the emcv polyprotein were not accelerated greatly by the dialysis system, de novo synthesis of viral rna was ...200717320977
development and validation of a real time pcr-based bioassay for quantification of neutralizing antibodies against human interferon-beta.there are two commonly employed types of bioassays for the detection of neutralizing antibodies (nabs) against interferon-beta (ifnbeta): the cytopatic effect assay (cpe), and the mxa (myxovirus resistance protein a) protein assay (mpa). this article describes a bioassay based on the real time pcr measurement of mrna that results from the induction, in cultured human cells, of the mxa gene by ifnbeta. serum samples from 104 patients with multiple sclerosis (ms) treated with ifnbeta were tested f ...200717335844
assessment of viral inactivation during ph 3.3 pepsin digestion and caprylic acid treatment of antivenoms.antivenoms are manufactured by the fractionation of animal plasma which may possibly be contaminated by infectious agents pathogenic to humans. this study was carried out to determine whether pre-existing antivenom production steps, as carried out by egyvac in egypt, may reduce viral risks. two typical manufacturing steps were studied by performing down-scaled viral inactivation experiments: (a) a ph 3.3 pepsin digestion of diluted plasma at 30 degrees c for 1h, and (b) a caprylic acid treatment ...200717363271
pdtc inhibits picornavirus polyprotein processing and rna replication by transporting zinc ions into cells.previously, it was shown that pyrrolidine dithiocarbamate (pdtc) inhibits proteolytic polyprotein processing and replication of human rhinovirus by transporting metal ions into cells. here, it is shown that pdtc also inhibits replication of two other picornaviruses: coxsackievirus b3 (cvb3), a closely related virus that belongs to the genus enterovirus, and mengovirus, an encephalomyocarditis virus strain that belongs to the genus cardiovirus, and that this inhibition is due to the dithiocarbama ...200717374764
serological evidence of encephalomyocarditis virus in pigs in ontario. 198517422556
antibody to encephalomyocarditis virus in pigs. 198717422925
ontario. encephalomyocarditis virus outbreak among suckling pigs. 198917423242
ontario. antibodies to encephalomyocarditis virus in aborted and stillborn pigs. 198917423427
a serosurvey of swine and free-living species on iowa farms for antibodies against encephalomyocarditis virus.swine and free-living nonporcine species from 20 iowa swine farms were surveyed for antibodies against encephalomyocarditis virus (emcv). the microtitration serum neutralization test was used, and antibody titers >/= 1:8 were considered positive. the overall prevalence in 267 sows in various groups was 37.8% (range 20-86%). the prevalence in sows maintained in total confinement was significantly lower than in sows not maintained in total confinement (p = 0.01). prevalence in sows was not associa ...199217424088
an infectious and selectable full-length replicon system with hepatitis c virus jfh-1 strain.aim: the hepatitis c virus (hcv) strain jfh-1 was cloned from a patient with fulminant hepatitis. a jfh-1 subgenomic replicon and full-length jfh-1 rna efficiently replicate in cultured cells. in this study, an infectious, selectable hcv replicon containing full-length jfh-1 cdna was constructed. methods: the full-genome replicon was constructed using the neomycin-resistant gene, emcv ires and wild-type jfh-1 cdna. huh7 cells were transfected with rna synthesized in vitro, and then cultured with ...200717437527
viral translation is coupled to transcription in sindbis virus-infected cells.during the late phase of sindbis virus infection, the viral subgenomic mrna is translated efficiently in bhk cells, whereas host protein synthesis is inhibited. however, transfection of in vitro-generated sindbis virus subgenomic mrna leads to efficient translation in uninfected bhk cells, whereas it is a poor substrate in infected cells. therefore, the structure of the subgenomic mrna itself is not sufficient to confer its translatability in infected cells. in this regard, translation of the su ...200717442713
efficient expression and purification of human interferon alpha2b in the methylotrophic yeast, pichia pastoris.the human interferon alpha2b (hifn-alpha2b) is the most widely used member of ifnalpha family, and it exerts many biological actions including broad-spectrum antiviral effects, inhibition of tumor cell proliferation and enhancement of immune functions. herein, the cdna coding for hifn-alpha2b has been cloned into the secreting expression organism pichia pastoris, and the high level expression of hifn-alpha2b has been achieved. sds-page and western blotting assays of culture broth from a methanol ...200717468009
partitioning and inactivation of viruses by the caprylic acid precipitation followed by a terminal pasteurization in the manufacturing process of horse immunoglobulins.caprylic acid (octanoic acid), has been used for over 50 years as a stabilizer of human albumin during pasteurization. in addition caprylic acid is of great interest, by providing the advantage of purifying mammalian immunoglobulins and clearing viruses infectivity in a single step. exploiting these two properties, we sequentially used the caprylic acid precipitation and the pasteurization to purify horse hyperimmune globulins used in the manufacturing of sérocytol. to evaluate the effectiveness ...200717470396
loss of dexd/h box rna helicase lgp2 manifests disparate antiviral responses.the dexd/h box rna helicase retinoic acid-inducible gene i (rig-i) and the melanoma differentiation-associated gene 5 (mda5) are key intracellular receptors that recognize virus infection to produce type i ifn. a third helicase gene, lgp2, is homologous to rig-i and mda5 but lacks a caspase activation and recruitment domain. we generated lgp2-deficient mice and report that the loss of this gene greatly sensitizes cells to cytosolic polyinosinic/polycytidylic acid-mediated induction of type i ifn ...200717475874
insights into rna virus mutant spectrum and lethal mutagenesis events: replicative interference and complementation by multiple point mutants.rna virus behavior can be influenced by interactions among viral genomes and their expression products within the mutant spectra of replicating viral quasispecies. here, we report the extent of interference of specific capsid and polymerase mutants of foot-and-mouth disease virus (fmdv) on replication of wild-type (wt) rna. the capsid and polymerase mutants chosen for this analysis had been characterized biochemically and structurally. upon co-electroporation of bhk-21 cells with wt rna and a te ...200717481660
oral administration of candesartan improves the survival of mice with viral myocarditis through modification of cardiac adiponectin expression.we examined the effects of the angiotensin ii receptor type 1 blocker candesartan on myocarditis injury in a murine model of acute myocarditis. we hypothesized that candesartan improves cardiac damage by inducing cardiac expression of adiponectin.200717484035
poly(a)-binding protein is differentially required for translation mediated by viral internal ribosome entry sites.the 3' poly(a) tail present on the majority of mature eukaryotic mrnas is an important regulator of protein synthesis and mrna stability. the poly(a) tail improves the efficiency of translation initiation through recruitment of pabp, enabling its interaction with eif4f located at the mrna 5'-end. recent evidence has also implicated a possible role for pabp and the poly(a) tract in translation control at steps beyond the initiation phase. similar to conventional mrnas, plus-strand rna virus genom ...200717652408
small self-rna generated by rnase l amplifies antiviral innate immunity.antiviral innate immunity is initiated in response to rna molecules that are produced in virus-infected cells. these rnas activate signalling cascades that activate the genes that encode alpha- and beta-interferon (ifn). signalling occurs through the interaction of the rnas with either of two pathogen recognition receptors, retinoic acid-inducible gene-i (rig-i, also known as ddx58) and melanoma differentiation associated gene-5 (mda5, also known as ifih1), which contain amino-terminal caspase a ...200717653195
microrna inhibition of translation initiation in vitro by targeting the cap-binding complex eif4f.micrornas (mirnas) play an important role in gene regulatory networks in animals. yet, the mechanistic details of their function in translation inhibition or messenger rna (mrna) destabilization remain controversial. to directly examine the earliest events in this process, we have developed an in vitro translation system using mouse krebs-2 ascites cell-free extract that exhibits an authentic mirna response. we show here that translation initiation, specifically the 5' cap recognition process, i ...200717656684
measles virus n protein inhibits host translation by binding to eif3-p40.the nonsegmented, negative-sense rna genome of measles virus (mv) is encapsidated by the virus-encoded nucleocapsid protein (n). in this study, we searched for n-binding cellular proteins by using mv-n as bait and screening the human t-cell cdna library by yeast two-hybrid assay and isolated the p40 subunit of eukaryotic initiation factor 3 (eif3-p40) as a binding partner. the interaction between mv-n and eif3-p40 in mammalian cells was confirmed by coimmunoprecipitation. since eif3-p40 is a tra ...200717686838
comparative aspects on the role of polypyrimidine tract-binding protein in internal initiation of hepatitis c virus and picornavirus rnas.we compared the effects of polypyrimidine tract-binding protein (ptb) on hepatitis c virus (hcv genotype iia), encephalomyocarditis virus (emcv) and poliovirus internal ribosome entry site (ires) activities in vitro. it bound strongly to emcv ires, but weakly to pv and hcv rnas. pv ires showed the strongest dependency to ptb and it showed less than one-tenth of ires activity after the immuno-depletion of ptb from hela s10 lysate with pre-coated anti-ptb igg beads, comparing to the normal igg bea ...200817706779
cardiovirus 2a protein associates with 40s but not 80s ribosome subunits during infection.host translation shutoff induced in picornavirus-infected cells is a well-known phenomenon. the mechanisms by which separate genera of the picornavirus family achieve this shutoff differ. this study examined alterations in the cellular translational components in hela cells infected with encephalomyocarditis virus (emcv), a cardiovirus. in agreement with previous reports, emcv induced a marked decrease in host mrna translation. the inhibition correlated with the appearance of a significantly enh ...200717728235
selection and analysis of mutations in an encephalomyocarditis virus internal ribosome entry site that improve the efficiency of a bicistronic flavivirus construct.flaviviruses have a positive-stranded rna genome, which simultaneously serves as an mrna for translation of the viral proteins. all of the structural and nonstructural proteins are translated from a cap-dependent cistron as a single polyprotein precursor. in an earlier study (k. k. orlinger, v. m. hoenninger, r. m. kofler, and c. w. mandl, j. virol. 80:12197-12208, 2006), it was demonstrated that an artificial bicistronic flavivirus genome, tbev-bc, in which the region coding for the viral surfa ...200717855533
back to basics: the untreated rabbit reticulocyte lysate as a competitive system to recapitulate cap/poly(a) synergy and the selective advantage of ires-driven translation.translation of most eukaryotic mrnas involves the synergistic action between the 5' cap structure and the 3' poly(a) tail at the initiation step. the poly(a) tail has also been shown to stimulate translation of picornavirus internal ribosome entry sites (ires)-directed translation. these effects have been attributed principally to interactions between eif4g and poly(a)-binding protein (pabp) but also to the participation of pabp in other steps during translation initiation. as the rabbit reticul ...200717881372
treatment options in myocarditis: what we know from experimental data and how it translates to clinical trials.although viral myocarditis has been mostly attributed to enterovirus and adenovirus infection until recently, the association with parvovirus b19 in europe and hepatitis c virus in asia has lately been noted. clinical trials of antiviral agents, such as interferons, are in progress. whereas immunosuppression with corticosteroids or cyclosporine is ineffective, immunosuppressors that do not promote viral replication, such as fty720, are promising new approaches. the inhibition of nuclear factor-k ...200717882370
high level protein expression in mammalian cells using a safe viral vector: modified vaccinia virus ankara.vaccinia virus vectors are attractive tools to direct high level protein synthesis in mammalian cells. in one of the most efficient strategies developed so far, the gene to be expressed is positioned downstream of a bacteriophage t7 promoter within the vaccinia genome and transcribed by the t7 rna polymerase, also encoded by the vaccinia virus genome. tight regulation of transcription and efficient translation are ensured by control elements of the escherichia coli lactose operon and the encepha ...200717892951
a highly efficient and robust in vitro translation system for expression of picornavirus and hepatitis c virus rna genomes.a krebs-2 cell-free extract that efficiently translates encephalomyocarditis virus (emcv) rna and extensively processes the viral polyprotein is also capable of supporting complete infectious emcv replication. the system displays high rna synthesis activity and de novo synthesis of virus up to titers of 2 x 10(7) to 6 x 10(7) plaque-forming units (pfu)/ml. the preparation of krebs-2 cell extract and methods of analysis of emcv-specific processes in vitro are described. we also demonstrate that t ...200717913619
in vitro reconstitution and biochemical characterization of translation initiation by internal ribosomal entry.the internal ribosomal entry sites (iress) of encephalomyocarditis virus (emcv) and related viruses promote initiation of translation by a noncanonical end-independent mechanism. to characterize this mechanism at the molecular level, we have developed biochemical approaches to reconstitute the process in vitro from individual purified components of the translation apparatus, developed methods to characterize steps in this process so that the functions of individual proteins can be characterized, ...200717913647
antibody-secreting cells in the central nervous system in an animal model of ms: phenotype, association with disability, and in vitro production of antibody.little is known about antibody production within the central nervous system, called intrathecal antibody production (itabp). mice infected with theiler's murine encephalomyocarditis virus (tmev) develop an immune-mediated demyelinating disease(tmev-idd), characterized by progressive weakness associated with robust itabp, cns inflammation and demyelination. tmev-idd represents an excellent model of human multiple sclerosis (ms), especially its progressive disability. the mechanism of the weakness ...200717919740
stimulation of picornavirus replication by the poly(a) tail in a cell-free extract is largely independent of the poly(a) binding protein (pabp).picornavirus infectivity is dependent on the rna poly(a) tail, which binds the poly(a) binding protein (pabp). pabp was reported to stimulate viral translation and rna synthesis. here, we studied encephalomyocarditis virus (emcv) and poliovirus (pv) genome expression in krebs-2 and hela cell-free extracts that were drastically depleted of pabp (96%-99%). although pabp depletion markedly diminished emcv and pv internal ribosome entry site (ires)-mediated translation of a polyadenylated luciferase ...200717942745
analysis of igg heavy chain to light chain ratio with mutant encephalomyocarditis virus internal ribosome entry site.immunoglobulin g (igg) is a heterotetrameric protein assembled from two identical heavy chain (hc) and two identical light chain (lc) polypeptides. the hc and lc folding and assembly are a crucial step for igg production. it is affected by the ratio of hc to lc expression (hc:lc). to date, the hc:lc ratio was analysed mainly by cotransfection of different amounts of two monocistronic hc and lc expression plasmids, an approach biased by different transfection efficiencies. to circumvent this prob ...200717951613
long term expression of bicistronic vector driven by the fgf-1 ires in mouse muscle.electrotransfer of plasmid dna into skeletal muscle is a promising strategy for the delivery of therapeutic molecules targeting various muscular diseases, cancer and lower-limb ischemia. internal ribosome entry sites (iress) allow co-expression of proteins of interest from a single transcriptional unit. iress are rna elements that have been found in viral rnas as well as a variety of cellular mrnas with long 5' untranslated regions. while the encephalomyocarditis virus (emcv) ires is often used ...200717963525
french maritime pine bark extract inhibits viral replication and prevents development of viral myocarditis.french maritime pine bark extract (pycnogenol) revealed diverse anti-inflammatory actions by an inhibition of nf-kappab-dependent gene expression. the aim of this study was to determine whether pycnogenol had a beneficial effect on viral myocarditis in mice.200717996829
[in process citation].cytokines are being increasingly recognised as important factors in the pathogenesis and pathophysiology of heart failure. elevated levels of circulating cytokines have been reported in patients with heart failure, and various cytokines have been shown to depress myocardial contractility in vitro and in vivo. in our murine model of congestive heart failure resulting from encephalomyocarditis virus infection, survival and myocardial damage were markedly improved by treatment with vesnarinone. ves ...199718031085
a new generation of pprig-based retroviral vectors.retroviral vectors are valuable tools for gene transfer. particularly convenient are ires-containing retroviral vectors expressing both the protein of interest and a marker protein from a single bicistronic mrna. this coupled expression increases the relevance of tracking and/or selection of transduced cells based on the detection of a marker protein. pap2 is a retroviral vector containing egfp downstream of a modified ires element of emcv origin, and a cmv enhancer-promoter instead of the u3 re ...200718053131
candesartan improves myocardial damage in obese mice with viral myocarditis and induces cardiac adiponectin.to clarify the mechanism of the effects of angiotensin ii receptor type 1 antagonist, candesartan, upon cardiac adiponectin in the combination of myocarditis with obesity, we examined obese kkay mice with acute viral myocarditis treated by candesartan and investigated cardiac adiponectin regulation.200818053594
molecular characterization of woodchuck type i interferons and their expression by woodchuck peripheral blood lymphocytes.interferon (ifn)-alpha and -beta are important antiviral mediators. ifn-alpha is widely used for the treatment of chronic hepatitis b. in our previous studies, a subtype of woodchuck ifn-alpha (wifn-alpha) was characterized and has been shown to be active in suppressing the replication of woodchuck hepatitis virus (whv) in vitro and vivo. here, we refined the analysis of the ifn-alpha/beta system of the woodchuck and studied the expression of wifn-alpha/beta in peripheral blood lymphocytes (pbls ...200818096400
protective immune response in mice vaccinated with a recombinant adenovirus containing capsid precursor polypeptide p1, nonstructural protein 2a and 3c protease genes (p12a3c) of encephalomyocarditis virus.encephalomyocarditis virus (emcv) infection can cause acute myocarditis and sudden death in pre-weaned piglets as well as severe reproductive failure in sows. in this study, two recombinant adenoviruses containing capsid precursor polypeptide p1 alone (ad-p1) and p1 plus nonstructural protein 2a and 3c protease coding regions (ad-p12a3c) of emcv were respectively constructed using replication-defective human adenovirus serotype 5 as vector, and their antibody responses and protective efficacies ...200818162265
a new liquid intravenous immunoglobulin with three dedicated virus reduction steps: virus and prion reduction capacity.a new 10% liquid human intravenous immunoglobulin (us trade name: gammagard liquid; european trade name: kiovig) manufactured by a process with three dedicated pathogen inactivation/removal steps (solvent/detergent treatment, 35-nm nanofiltration and low ph/elevated temperature incubation) was developed. the ability of the manufacturing process to inactivate/remove viruses and prions was investigated.200818167162
optimization strategy for plasmid dnas containing multiple-epitopes of foot-and-mouth disease virus by cis-expression with il-2.to optimize previous candidate dna vaccine, a cis-expression plasmid dna encoding two genes, human il-2 and multiple-epitopes genes of foot-and-mouth disease virus (fmdv) was constructed with internal ribosome entry site (ires) from encephalomyocarditis virus (emcv) and intramuscularly inoculated into mice at 1-week interval. specific antibodies in serum and cytokines (il-2, il-4 and ifn-gamma) from splenocytes were detected by indirect elisa. splenocytes proliferation rate was determined by a s ...200818191307
functional analysis of picornavirus 2b proteins: effects on calcium homeostasis and intracellular protein trafficking.the family picornaviridae consists of a large group of plus-strand rna viruses that share a similar genome organization. the nomenclature of the picornavirus proteins is based on their position in the viral rna genome but does not necessarily imply a conserved function of proteins of different genera. the enterovirus 2b protein is a small hydrophobic protein that, upon individual expression, is localized to the endoplasmic reticulum (er) and the golgi complex, reduces er and golgi complex ca(2+) ...200818216106
specific small interfering rnas-mediated inhibition of replication of porcine encephalomyocarditis virus in bhk-21 cells.encephalomyocarditis virus (emcv) is recognized as a pathogen inducing acute myocarditis and sudden death in preweaned piglets and severe reproductive failure in sows. in this study, eight specific small interfering rna (sirna) duplexes targeting different genomic regions of emcv bjc3 were designed and their ability to inhibit virus replication in bhk-21 cells was investigated. the results showed that bhk-21 cells transfected with sirna duplexes to 2c gene (jh-4,666, bjc-1,739), 2b gene (bjc-807 ...200818243347
translational control of the innate immune response through irf-7.transcriptional activation of cytokines, such as type-i interferons (interferon (ifn)-alpha and ifn-beta), constitutes the first line of antiviral defence. here we show that translational control is critical for induction of type-i ifn production. in mouse embryonic fibroblasts lacking the translational repressors 4e-bp1 and 4e-bp2, the threshold for eliciting type-i ifn production is lowered. consequently, replication of encephalomyocarditis virus, vesicular stomatitis virus, influenza virus an ...200818272964
suppression of interferon (ifn)-inducible genes and ifn-mediated functional responses in bcr-abl-expressing cells.the interferons (ifns) are cytokines that play key roles in host defense against viral infections and immune surveillance against cancer. we report that bcr-abl transformation of hematopoietic cells results in suppression of ifn-dependent responses, including transcription of ifn-inducible genes and generation of ifn-mediated antiviral effects. bcr-abl transformation suppresses expression of several ifn-regulated genes containing ifn-sensitive response element (isre) or gas elements in their pro ...200818287094
role of the akt pathway in mrna translation of interferon-stimulated genes.multiple signaling pathways are engaged by the type i and ii ifn receptors, but their specific roles and possible coordination in the generation of ifn-mediated biological responses remain unknown. we provide evidence that activation of akt kinases is required for ifn-inducible engagement of the mtor/p70 s6 kinase pathway. our data establish that akt activity is essential for up-regulation of key ifn-alpha- and ifn-gamma-inducible proteins, which have important functional consequences in the ind ...200818339807
efficient gene transfer in skeletal muscle with aav-derived bicistronic vector using the fgf-1 ires.iress (internal ribosome entry sites) are rna elements behaving as translational enhancers in conditions of global translation blockade. iress are also useful in biotechnological applications as they allow expression of several genes from a single mrna. up to now, most ires-containing vectors use the ires from encephalomyocarditis virus (emcv), highly active in transiently transfected cells but long and not flexible in its positioning relative to the gene of interest. in contrast, several iress ...200818369321
nmd resulting from encephalomyocarditis virus ires-directed translation initiation seems to be restricted to cbp80/20-bound mrna.nonsense-mediated messenger rna decay (nmd) generally degrades mrnas that prematurely terminate translation as a means of quality control. nmd in mammalian cells targets newly spliced mrna that is bound by the cap-binding protein heterodimer cbp80/20 and one or more post-splicing exon junction complexes during a pioneer round of translation. nmd targets mrna that initiates translation using the encephalomyocarditis virus (emcv) internal ribosome entry site (ires), therefore nmd might target not ...200818369367
cellular prion protein prevents brain damage after encephalomyocarditis virus infection in mice.cellular prion protein (prp(c)), a cell-surface glycoprotein normally associated with neurons, is also expressed in other cell types such as glia and lymphocytes. to further elucidate these roles of prp(c), wild-type prion protein gene (prnp(+/+)) mice and prnp-deficient (prnp(-/-)) mice were infected with encephalomyocarditis virus b variant (emcv-b) via an intracranial route. emcv-b causes encephalitis and apoptotic cell death in vivo. histopathological studies revealed that prnp(+/+) mice inf ...200818408883
multiple kinases in the interferon-gamma response.janus kinases (jaks) and signal transducers and activators of transcription (stats) are essential for responses to interferons (ifns), most cytokines, and some growth factors. jak/stat signaling is not, however, sufficient for a full ifn-gamma response. here, a convenient, robust, and quantitative flow cytometry-based kinome-wide sirna screen has identified nine additional kinases as required for the ifn-gamma class ii hla response, seven for an antiviral response, and two for the cytopathic res ...200818417454
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