Publications

TitleAbstractYear
Filter
PMID(sorted descending)
Filter
l-tryptophan-kynurenine pathway metabolites regulate type i ifns of acute viral myocarditis in mice.the activity of ido that catalyzes the degradation of tryptophan (trp) into kynurenine (kyn) increases after diseases caused by different infectious agents. previously, we demonstrated that ido has an important immunomodulatory function in immune-related diseases. however, the pathophysiological role of ido following acute viral infection is not fully understood. to investigate the role of ido in the l-trp-kyn pathway during acute viral myocarditis, mice were infected with encephalomyocarditis v ...201222422885
inhibition of hepatitis b virus replication by phospholipid scramblase 1 in vitro and in vivo.human phospholipid scramblase 1 (plscr1) is an α/β interferon-inducible protein that mediates antiviral activity against rna viruses including vesicular stomatitis virus (vsv) and encephalomyocarditis virus (emcv). in the present study, we investigated the antiviral activity of plscr1 protein against hbv (hepatitis b virus). firstly, plscr1 mrna and protein expression was found to be downregulated in hepg2 cells after hbv infection. then by performing co-transient-transfection experiments in cel ...201222342889
promotion of viral internal ribosomal entry site-mediated translation under amino acid starvation.cap-dependent and internal ribosomal entry site (ires)-mediated translation are regulated differently within cells. viral ires-mediated translation often remains active when cellular cap-dependent translation is severely impaired under cellular stresses induced by virus infection. to investigate how cellular stresses influence the efficiency of viral ires-mediated translation, we used a bicistronic luciferase reporter construct harbouring ires elements from the following viruses: encephalomyocar ...201222302880
a vaccine candidate for eastern equine encephalitis virus based on ires-mediated attenuation.to develop an effective vaccine against eastern equine encephalitis (eee), we engineered a recombinant eee virus (eeev) that was attenuated and capable of replicating only in vertebrate cells, an important safety feature for live vaccines against mosquito-borne viruses. the subgenomic promoter was inactivated with 13 synonymous mutations and expression of the eeev structural proteins was placed under the control of an internal ribosomal entry site (ires) derived from encephalomyocarditis virus ( ...201222222869
effects of magnesium ions on two emcv ires key activity fragments.using nmr magnetization transfer from water and ammonia-catalyzed exchange of the imino protons, changes have been monitored in base-pair kinetics induced by mg(2 + ) in two key activity fragments r(caccuggcgacaggug) and r(ggccaaaagcc) of the encephalomyocarditis virus internal ribosome entry site. for r(caccuggcgacaggug), the addition of mg(2 + ) reveals two types of base-pairs: r(u(545)·a) and r(g(546)·c), in the first category, have lifetimes only slightly higher in the presence of mg(2 + ), ...201122210961
in vitro inhibition of influenza a virus infection by marine microalga-derived sulfated polysaccharide p-kg03.the sulfated polysaccharide, p-kg03, purified from the marine microalga, gyrodinium impudium, is a unique compound comprising homogenous galactose units conjugated to uronic acid and sulfated groups. although previous studies showed that p-kg03 suppresses tumor cell growth and infection by encephalomyocarditis virus, its effect against enveloped virus infection and the biological mechanism of action have not been elucidated. in this report, the inhibitory activity of p-kg03 against influenza vir ...201122197247
latent hit series hidden in high-throughput screening data.recently a novel method termed compound set enrichment (cse) has been described that uses the activity distribution of a structural class of compounds to identify hit series from primary screening data. this report describes how this method can be used to identify such hit series, even when no hits according to conventional hit-calling methods for a given structural class are present in the data set. such series, which were called latent hit series, were identified prospectively in a cell-based ...201122185196
SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage.SARS coronavirus (SCoV) nonstructural protein (nsp) 1, a potent inhibitor of host gene expression, possesses a unique mode of action: it binds to 40S ribosomes to inactivate their translation functions and induces host mRNA degradation. Our previous study demonstrated that nsp1 induces RNA modification near the 5'-end of a reporter mRNA having a short 5' untranslated region and RNA cleavage in the encephalomyocarditis virus internal ribosome entry site (IRES) region of a dicistronic RNA template ...201122174690
A new splice variant of the human guanylate-binding protein 3 mediates anti-influenza activity through inhibition of viral transcription and replication.Guanylate-binding proteins (GBPs) belong to the family of large GTPases that are induced in response to interferons. GBPs contain an N-terminal globular GTPase domain and a C-terminal a-helical regulatory domain that are connected by a short middle domain. Antiviral activity against vesicular stomatitis virus and encephalomyocarditis virus has been shown for hGBP-1; however, no anti-influenza virus properties for GBPs have been described to date. Here we show that hGBP-1 and hGBP-3 possess anti- ...201122106366
inhibition of encephalomyocarditis virus replication by shrna targeting 1d and 3ab genes in vitro and in vivo.encephalomyocarditis virus (emcv) could infect many host species and cause acute myocarditis and sudden death in pre-weaned piglets. it was necessary to develop new antiviral strategies for the treatment of the virus infection. here, four plasmids expressing shrna (small hairpin rna) targeted to 1d or 3ab protein genes of emcv were constructed and their inhibition efficiency on the replication of emcv was evaluated in both bhk21 cells and mice. the results showed that three out of those four shr ...201122052534
Ribosomal frameshifting into an overlapping gene in the 2B-encoding region of the cardiovirus genome.The genus Cardiovirus (family Picornaviridae) currently comprises the species Encephalomyocarditis virus (EMCV) and Theilovirus. Cardioviruses have a positive-sense, single-stranded RNA genome that encodes a large polyprotein (L-1ABCD-2ABC-3ABCD) that is cleaved to produce approximately 12 mature proteins. We report on a conserved ORF that overlaps the 2B-encoding sequence of EMCV in the +2 reading frame. The ORF is translated as a 128-129 amino acid transframe fusion (2B*) with the N-terminal 1 ...201122025686
ccr5 regulates inflammatory gene expression in response to encephalomyocarditis virus infection.encephalomyocarditis virus (emcv) is capable of stimulating inflammatory gene expression by macrophages as a result of interactions between emcv capsid proteins and cell surface receptors. in this study, biochemical and genetic approaches identified a role for ccr5, a chemokine receptor, in transducing the signals of emcv infection that result in the expression of inflammatory genes in macrophages. antibody neutralization and gene knockout strategies were used to show that the presence of ccr5 i ...201122001348
promyelocytic leukemia isoform iv confers resistance to encephalomyocarditis virus via the sequestration of 3d polymerase in nuclear bodies.promyelocytic leukemia (pml) protein is the organizer of nuclear matrix-associated nuclear bodies (nbs), and its conjugation to the small ubiquitin-like modifier (sumo) is required for the formation of these structures. several alternatively spliced pml transcripts from a single pml gene lead to the production of seven pml isoforms (pml isoform i [pmli] to vii [pmlvii]), which all share a n-terminal region that includes the rbcc (ring, b boxes, and a α-helical coiled-coil) motif but differ in th ...201121994459
encephalomyocarditis virus may use different pathways to initiate infection of primary human cardiomyocytes.encephalomyocarditis virus (emcv) can infect a wide range of vertebrate species including swine and non-human primates, but few data are available for humans. we therefore wanted to gain further insight into the mechanisms involved in emcv infection of human cells. for this purpose, we analyzed the permissiveness of primary human cardiomyocytes towards two strains of emcv; a pig myocardial strain (b279/95) and a rat strain (1086c). in this study, we show that both strains productively infect pri ...201121989795
conditional transgenic expression of tir-domain-containing adaptor-inducing interferon-β (trif) in the adult mouse heart is protective in acute viral myocarditis.tir-domain-containing adaptor-inducing interferon-β (trif) plays a major role in toll-like receptor 3 (tlr3) mediated signaling. mice deficient in tlr3 and trif have been shown to be highly susceptible to enterovirus-induced myocardial injury. these mice have decreased production of antiviral cytokines and increased viral replication in the heart. therefore, we hypothesized that conditional overexpression of trif would change cardiac myocyte susceptibility to virus infection by augmenting the an ...201121956162
Synthesis of encephalomyocarditis virus in a cell-free system: from DNA to RNA virus in one tube.Virus particles are used in vaccination, drug delivery, and material sciences. Here we devised a system where the RNA virus encephalomyocarditis virus (EMCV) is synthesized from DNA templates in vitro. When a plasmid or a PCR product harboring the full-length cDNA of EMCV in the T7 promoter/terminator unit was incubated in a HeLa cell extract supplemented with T7 RNA polymerase, EMCV was produced within 4 h at an efficiency of over 10-fold compared with the system programmed with the EMCV RNA. T ...201221952914
Unusual loop-sequence flexibility of the proximal RNA replication element in EMCV.Picornaviruses contain stable RNA structures at the 5' and 3' ends of the RNA genome, OriL and OriR involved in viral RNA replication. The OriL RNA element found at the 5' end of the enterovirus genome folds into a cloverleaf-like configuration. In vivo SELEX experiments revealed that functioning of the poliovirus cloverleaf depends on a specific structure in this RNA element. Little is known about the OriL of cardioviruses. Here, we investigated structural aspects and requirements of the apical ...201121935472
antiviral activity of distictella elongata (vahl) urb. (bignoniaceae), a potentially useful source of anti-dengue drugs from the state of minas gerais, brazil.to investigate the in vitro antiviral activity of distictella elongata (vahl) urb. ethanol extracts from leaves (lee), fruits (fee), stems and their main components.201121895729
encephalomyocarditis virus 2a protein is required for viral pathogenesis and inhibition of apoptosis.the encephalomyocarditis virus (emcv), a picornaviridae virus, has a wide host spectrum and can cause various diseases. emcv virulence factors, however, are as yet ill defined. here, we demonstrate that the emcv 2a protein is essential for the pathogenesis of emcv. infection of mice with the b279/95 strain of emcv resulted in acute fatal disease, while the clone c9, derived by serial in vitro passage of the b279/95 strain, was avirulent. c9 harbored a large deletion in the gene encoding the 2a p ...201121849462
novel chikungunya vaccine candidate with an ires-based attenuation and host range alteration mechanism.chikungunya virus (chikv) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. as with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. therefore, vaccines remain the best strategy to prevent most vector-borne diseases. ideally, vaccines for diseases of resource-limited countries should combine lo ...201121829348
studies of inactivation of encephalomyocarditis virus, m13 bacteriophage, and salmonella typhimurium by using a visible femtosecond laser: insight into the possible inactivation mechanisms.we report experimental results on the inactivation of encephalomyocarditis virus, m13 bacteriophage, and salmonella typhimurium by a visible femtosecond laser. our results suggest that inactivation of virus and bacterium by a visible femtosecond laser involves completely different mechanisms. inactivation of viruses by a visible femtosecond laser involves the breaking of hydrogen/hydrophobic bonds or the separation of the weak protein links in the protein shell of a viral particle. in contrast, ...201121806295
translation of viral mrna without active eif2: the case of picornaviruses.previous work by several laboratories has established that translation of picornavirus rna requires active eif2a for translation in cell free systems or after transfection in culture cells. strikingly, we have found that encephalomyocarditis virus protein synthesis at late infection times is resistant to inhibitors that induce the phosphorylation of eif2a whereas translation of encephalomyocarditis virus early during infection is blocked upon inactivation of eif2a by phosphorylation induced by a ...201121779397
the leader protein of cardioviruses inhibits stress granule assembly.stress granules (sg) are cytoplasmic aggregates of stalled translation pre-initiation complexes forming in cells exposed to various environmental stresses. here, we show that stress granules assemble in cells infected with theiler's murine encephalomyelitis virus (tmev) mutants carrying alterations in the leader (l) protein, but not in cells infected with wild-type tmev. stress granules also formed in stat1-deficient cells, suggesting that sg formation was not a consequence of increased type-i i ...201121752908
saffold cardioviruses in children with diarrhea, thailand.to the editor: cardioviruses currently consist of at least 3 viruses: theiler murine encephalomyocarditis virus, encephalomyocarditis virus, and saffold virus (safv) (1-4). saffold cardiovirus in the family picornaviridae was isolated and identified from fecal specimens of a child with fever of unknown origin in the united states (3).201121749802
Involvement of Noxa in mediating cellular ER stress responses to lytic virus infection.Noxa is a Bcl-2 homology domain-containing pro-apoptotic mitochondrial protein. Noxa mRNA and protein expression are upregulated by dsRNA or virus, and ectopic Noxa expression enhances cellular sensitivity to virus or dsRNA-induced apoptosis. Here we demonstrate that Noxa null baby mouse kidney (BMK) cells are deficient in normal cytopathic response to lytic viruses, and that reconstitution of the knockout cells with wild-type Noxa restored normal cytopathic responses. Noxa regulation by virus m ...201121742363
the effect of fty720 in the theiler's virus model of multiple sclerosis.fty720 (fingolimod) has demonstrated efficacy in multiple sclerosis (ms). we evaluated the effects of fty720 on progressive disability, viral load, and antibody responses in mice infected with theiler's murine encephalomyocarditis virus (tmev). fty720 and phosphorylated fty720 (fty720-p) were detected in the brain after intraperitoneal injection of the drug. bioactivity of fty720 was confirmed by reduced numbers of mononuclear cells in the spleen and blood after treatment. no significant differe ...201121726878
knockdown of usp18 increases alpha 2a interferon signaling and induction of interferon-stimulating genes but does not increase antiviral activity in huh7 cells.the current standard of care for hepatitis c virus (hcv) patients is cotreatment with human alpha interferon (ifn-α) and ribavirin. the host factor usp18 functions to regulate the interferon signaling pathway by acting as an off-switch. in order to understand whether the inhibition of usp18 represents a valid target for the enhancement of interferon treatment for chronic viral diseases, we have used a wide range of rna interference (rnai) reagents to suppress usp18 gene expression in huh7 cell l ...201121709085
compare the differences of synonymous codon usage between the two species within cardiovirus.abstract:201121708006
alteration of encephalomyocarditis virus pathogenicity due to a mutation at position 100 of vp1.encephalomyocarditis virus (emcv) infection leads to many diseases including encephalitis, myocarditis and diabetes in its natural host, the mouse. in this study, we generated four cdna clones with a point mutation at position 100 of vp1. the amino acids isoleucine, alanine, serine and proline were substituted with threonine in the four different clones of emcv strain bjc3 by site-specific mutagenesis, and viable viruses were rescued. although all mutants and wild-type viruses display different ...201121706414
kshv virf-2 inhibits type 1 interferon signalling by targeting isgf-3.kaposi's sarcoma-associated herpesvirus (kshv) encodes four viral interferon regulatory factors (virf-1-4). we investigated the mechanism and consequences of virf-2-mediated inhibition of interferon-response element (isre) signalling following type i interferon (ifn) induction. western blot and electrophoretic mobility shift assays identified the interferon stimulated gene factor-3 (isgf-3) components stat-1 and irf-9 as the proximal targets of virf-2 activity. the biological significance of vir ...201121697347
immunogenicity of an interferon-beta1a product.in order to determine whether blastoferon®, a biosimilar interferon (ifn)- beta 1a formulation, shares epitopes with other known ifn-beta products, a series of neutralization bioassays were performed with a set of well-characterized anti-ifn- beta monoclonal antibodies and human sera (world health organization reference reagents). the bioassay was the interferon-induced inhibition of virus cytopathic effect on human cells in culture (emc virus and a-549 cells). computer-calculated results were r ...201121658324
epizootic myocarditis associated with encephalomyocarditis virus in a group of rhesus macaques (macaca mulatta).six cases of fatal myocarditis associated with encephalomyocarditis virus occurred over a 14-month period in a group of outdoor-housed juvenile rhesus macaques. all animals were younger than 3 years of age and died or were euthanized following acute onset of dyspnea or pulmonary effusion (3 of 6) or were found dead without premonitory signs (3 of 6). gross findings included pulmonary congestion (6 of 6), variable degrees of pleural effusion (4 of 6), multifocal pale tan foci throughout the myoca ...201121653204
inhibition of rnase l and pkr by sunitinib impairs antiviral innate immunity.rnase l and pkr are effectors of the interferon antiviral response that share homology in their pseudokinase and protein kinase domains, respectively. sunitinib is an orally available, atp competitive inhibitor of vegf-r and pdgf-r used clinically to suppress angiogenesis and tumor growth. sunitinib also impacts ire1, an endoplasmic reticulum protein involved in the unfolded protein response that is closely-related to rnase l. here we report that sunitinib is a potent inhibitor of both rnase l a ...201121636578
recombinant protein hydrazides: application to site-specific protein pegylation.here, we describe a novel method for the site-specific c-terminal pegylation of recombinant proteins. this general approach exploits chemical cleavage of precursor intein-fusion proteins with hydrazine to directly produce recombinant protein hydrazides. this unique functionality within the protein sequence then facilitates site-specific c-terminal modification by hydrazone-forming ligation reactions. this approach was used to generate folded, site-specifically c-terminal pegylated ifnalpha2b and ...201121618993
the protease-sensitive loop of the vesicular stomatitis virus matrix protein is involved in virus assembly and protein translation.to study the contribution of the protease-sensitive loop of the vsv m protein in virus assembly we recovered recombinant vsv (rvsv) with mutations in this region and examined virus replication. mutations in the highly conserved lxd motif (aa 123-125) resulted in reduced virion budding, reduced virus titers and enhanced m protein exchange with m-ribonucleocapsid complexes (m-rnps), suggesting that the mutant m proteins were less tightly associated with rnp skeletons. in addition, viral protein sy ...201121596416
adaptation of saffold virus-2 for high-titer growth in mammalian cells.saffold viruses (safv) are a recently discovered group of human cardioviruses closely related to the theiler's murine encephalomyelitis viruses (tmev). unlike tmev and encephalomyocarditis virus, each of which is monotypic, safv are genetically diverse and include at least eight genotypes. to date, only safv-3 has been grown efficiently in mammalian cells in vitro. here, we report the successful adaptation of safv-2 for efficient growth in hela cells after 13 passages in the interferon α/β-defic ...201121543476
activation of picornaviral iress by ptb shows differential dependence on each ptb rna-binding domain.polypyrimidine tract binding protein (ptb) is an rna-binding protein with four rna-binding domains (rbds). it is a major regulator of alternative splicing and also stimulates translation initiation at picornavirus iress (internal ribosome entry sites). the sites of interaction of each rbd with two picornaviral iress have previously been mapped. to establish which rbd-ires interactions are essential for ires activation, point mutations were introduced into the rna-binding surface of each rbd. thr ...201121518806
microbiological safety of porcine islets: comparison with source pig.pig islet donors intended for clinical xenotransplantation for the treatment of diabetes must meet stringent conditions. among others, viruses with the potential to cross the species barrier should be excluded from the herd: this list includes encephalomyocarditis virus (emcv), hepatitis e virus (hev), porcine cytomegalovirus (pcmv) and porcine γ-lymphotropic herpesvirus (plhv). as an islet product is isolated from the pancreas and then subjected to culture before implantation, the question is r ...201121496116
immunogenicity and safety of virus-like particle of the porcine encephalomyocarditis virus in pig.abstract:201121492483
autophagy promotes the replication of encephalomyocarditis virus in host cells.a growing number of studies have demonstrated that autophagy has a diverse role in the infection process of different pathogens. however, to date, it is unknown whether autophagy is activated in encephalomyocarditis virus (emcv)-infected host cells, and if so, what its role is in this process. in the present study, we first demonstrated that emcv infection significantly increases the number of double- and single-membrane vesicles in the cytoplasm of host cells. it was then confirmed that these o ...201121460631
possible role of phosphoinositide-3-kinase in mx1 protein translation and antiviral activity of interferon-omega-stimulated hela cells.interferon ? (ifn-?), a cytokine released during innate immune activation, is well known for promoting direct antiviral responses; however, the possible signal pathways that are initiated by ifn-? binding to the type i ifn receptors have not been fully studied. here, we provide evidence that activation of phosphoinositide-3-kinase/protein kinase b (pi3k/akt) signaling plays a pivotal role in the generation of ifn-?-mediated biological responses. we found that ly294002 (pi3k inhibitor)-attenuated ...201121430412
rna sensor-induced type i ifn prevents diabetes caused by a ß cell-tropic virus in mice.viral infections have been linked to the onset of type i diabetes (t1d), with viruses postulated to induce disease directly by causing ß cell injury and subsequent release of autoantigens and indirectly via the host type i interferon (ifn-i) response triggered by the virus. consistent with this, resistance to t1d is associated with polymorphisms that impair the function of melanoma differentiation associated gene-5 (mda5), a sensor of viral rna that elicits ifn-i responses. in animal models, tri ...201121403398
efficient co-expression of bicistronic proteins in mesenchymal stem cells by development and optimization of a multifunctional plasmid.local synthesis of interferon within b16 tumors mediates anti-tumor effects. based on reports that stem cells are recruited to tumors, and because systemic administration of interferon causes dose-limiting undesirable side effects, we wanted to improve the anti-tumor effects of interferon while simultaneously minimizing its systemic side effects by employing mesenchymal stem cells (mscs) as tumor-localized ectopic producers of interferon. many vectors exist to fulfill this purpose, but their tra ...201121401924
prevalence and risk factors for encephalomyocarditis virus infection in peru.although encephalomyocarditis virus (emcv) infection has been commonly documented among domestic animals, less is known about emcv transmission among humans. recently, we described the isolation of emcv from two febrile patients in peru. to further investigate emcv transmission in peru, we screened febrile patients reporting to health clinics in peru for serological evidence of recent emcv infection. we also conducted a serological survey for emcv-neutralizing antibodies in the city of iquitos, ...201121395427
in vitro and in vivo comparison of viral and cellular internal ribosome entry sites for bicistronic vector expression.bicistronic vectors are essential to achieve efficient expression of multiple genes in gene therapy protocols and biomedical applications. internal ribosome entry site (ires) elements have been utilized to initiate expression of an additional protein from a bicistronic vector. the ires element commonly used in current bicistronic vectors originates from the encephalomyocarditis virus (emcv). as ires-mediated translation is dependent on availability of ires trans-acting factors, which vary betwee ...201121368899
encephalomyocarditis virus mortality in semi-wild bonobos (pan panicus).fatal myocarditis from encephalomyocarditis virus (emcv) infection has previously been identified in sporadic and epidemic forms in many species of captive non-human primates probably including one bonobo (pan paniscus).201121323673
the irf-3/bax-mediated apoptotic pathway, activated by viral cytoplasmic rna and dna, inhibits virus replication.induction of apoptosis in cells infected by sendai virus (sev), which triggers the cytosolic rig-i pathway, requires the presence of interferon regulatory factor 3 (irf-3). independent of irf-3's transcriptional role, a novel irf-3 activation pathway causes its interaction with the proapoptotic protein bax and its mitochondrial translocation to induce apoptosis. here we report that two other rna viruses, vesicular stomatitis virus (vsv) and encephalomyocarditis virus (emcv), may also activate th ...201121307205
common conformational changes induced in type 2 picornavirus iress by cognate trans-acting factors.type 2 internal ribosomal entry sites (iress) of encephalomyocarditis virus (emcv), foot-and-mouth disease virus (fmdv) and other picornaviruses comprise five major domains h-l. initiation of translation on these iress begins with specific binding of the central domain of initiation factor, eif4g to the j-k domains, which is stimulated by eif4a. eif4g/eif4a then restructure the region of ribosomal attachment on the ires and promote recruitment of ribosomal 43s pre-initiation complexes. in additi ...201121306989
the nlrp3 inflammasome detects encephalomyocarditis virus and vesicular stomatitis virus infection.inflammasomes are cytosolic protein complexes that regulate caspase-1 activation and the secretion of interleukin-1ß (il-1ß) and il-18. several different inflammasome complexes have been identified, but the nlrp3 inflammasome is particularly notable because of its central role in diseases of inflammation. recent work has demonstrated an essential role for the nlrp3 inflammasome in host defense against influenza virus. we show here that two other rna viruses, encephalomyocarditis virus (emcv) and ...201121289120
mitochondrial membrane potential is required for mavs-mediated antiviral signaling.mitochondria, dynamic organelles that undergo cycles of fusion and fission, are the powerhouses of eukaryotic cells and are also involved in cellular innate antiviral immunity in mammals. mitochondrial antiviral immunity depends on activation of the cytoplasmic retinoic acid-inducible gene i (rig-i)-like receptor (rlr) signaling pathway and the participation of a mitochondrial outer membrane adaptor protein called mavs (mitochondrial antiviral signaling). we found that cells that lack the abilit ...201121285412
recognition of cytoplasmic rna results in cathepsin-dependent inflammasome activation and apoptosis in human macrophages.dsrna is an important pathogen-associated molecular pattern that is primarily recognized by cytosolic pattern-recognition receptors of the innate-immune system during virus infection. this recognition results in the activation of inflammasome-associated caspase-1 and apoptosis of infected cells. in this study, we used high-throughput proteomics to identify secretome, the global pattern of secreted proteins, in human primary macrophages that had been activated through the cytoplasmic dsrna-recogn ...201121257972
pandemic 2009 h1n1 influenza virus is resistant to the antiviral activity of several interferon alpha subtypes.interferons (ifns) are critically important in the control of influenza a virus infections. to better understand the pathogenic characteristics of the pandemic 2009 h1n1 influenza virus (ph1n1) from an innate immunity viewpoint, we investigated whether in vitro ph1n1 is sensitive to the antiviral activity of ifn beta, leukocyte ifn alpha, and several ifn alpha subtypes in a human lung adenocarcinoma epithelial cell line under single-growth cycle conditions. the results showed that 50% inhibitory ...201121235413
a novel role for ifn-stimulated gene factor 3ii in ifn-γ signaling and induction of antiviral activity in human cells.type i (e.g., ifn-α, ifn-β) and type ii ifns (ifn-γ) have antiviral, antiproliferative, and immunomodulatory properties. both types of ifn signal through the jak/stat pathway to elicit antiviral activity, yet ifn-γ is thought to do so only through stat1 homodimers, whereas type i ifns activate both stat1- and stat2-containing complexes such as ifn-stimulated gene factor 3. in this study, we show that ifn-stimulated gene factor 3 containing unphosphorylated stat2 (isgf3(ii)) also plays a role in ...201021178011
mutational analysis of the emcv 2a protein identifies a nuclear localization signal and an eif4e binding site.cardioviruses have a unique 2a protein (143 aa). during genome translation, the encephalomyocarditis virus (emcv) 2a is released through a ribosome skipping event mitigated through c-terminal 2a sequences and by subsequent n-terminal reaction with viral 3c(pro). although viral replication is cytoplasmic, mature 2a accumulates in nucleoli shortly after infection. some protein also transiently associates with cytoplasmic 40s ribosomal subunits, an activity contributing to inhibition of cellular ca ...201021145089
exendin-4, a glucagon-like peptide-1 receptor agonist, suppresses pancreatic β-cell destruction induced by encephalomyocarditis virus.viral infection is one of the important factors for the pathogenesis of type 1 diabetes. particularly, in fulminant type 1 diabetes, rapid β-cell destruction is suggested to be triggered by viral infection. recently, glucagon-like peptide 1 (glp-1) receptor agonists have been reported to have direct beneficial effects on β-cells, such as anti-apoptotic effect, increasing β-cell mass, and improvement of β-cell function. however, their effects on β-cell destruction induced by viral infections have ...201021144822
alkylated porphyrins have broad antiviral activity against hepadnaviruses, flaviviruses, filoviruses, and arenaviruses.we screened ∼2,200 compounds known to be safe in people for the ability to reduce the amount of virion-associated hepatitis b virus (hbv) dna in the culture medium of producer cells. these efforts led to the discovery of an alkylated porphyrin, chlorophyllide, as the compound that achieved the greatest reduction in signal. here we report that chlorophyllide directly and quantitatively disrupted hbv virions at micromolar concentrations, resulting in the loss of all detectable virion dna, without ...201021135183
the burden of obesity on infectious disease.the world is now experiencing an epidemic of obesity. although the effects of obesity on the development of metabolic and cardiovascular problems are well studied, much less is known about the impact of obesity on immune function and infectious disease. studies in obese humans and with obese animal models have repeatedly demonstrated impaired immune function, including decreased cytokine production, decreased response to antigen/mitogen stimulation, reduced macrophage and dendritic cell function ...201021127339
anti-infective activities of pelargonium sidoides (eps® 7630): effects of induced no production on leishmania major in infected macrophages and antiviral effects as assessed in a fibroblast-virus protection assay.eps® 7630 is an aqueous-ethanolic extract of the roots of pelargonium sidoides, employed in the treatment of upper respiratory tract infections. its anti-infective activity is supposed to be associated with the activation of the nonspecific immune system. using leishmania major gfp-infected murine bmmφ, the no production of eps® 7630-activated macrophages was correlated with the reduction of the gfp signal measured at single cell levels using flow cytometry. the anti-infectious effect of eps® 76 ...201021104606
further observations on the virus of encephalomyocarditis. 194621064731
antiviral effects of a transgenic rna-dependent rna polymerase.transgenic expression of the rna-dependent rna polymerase 3d(pol) inhibited infection of theiler's murine encephalitis virus (tmev), a picornavirus from which it was derived. here, we infected 3d(pol) transgenic mice with another picornavirus, as well as an alphaherpesvirus and a rhabdovirus. 3d(pol) transgenic fvb mice had significantly lower viral loads and survived longer after infection with all three types of viruses than nontransgenic fvb mice. viral inhibition among three different types ...201020962089
viral induction of zac1b through tlr3- and irf3-dependent pathways.zinc finger protein regulator of apoptosis and cell cycle arrest (zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. in spite of the important potential functions attributed to zac1, little is known of its physiological regulation and biological function. we discovered that variant zac1b was expressed in murine embryonic fibroblasts (mefs) treated with polyriboinosinic polyribocytidylic acid [poly(i:c)], a synthetic double-stranded rna. th ...201020947170
nucleoporin phosphorylation triggered by the encephalomyocarditis virus leader protein is mediated by mitogen-activated protein kinases.cardioviruses disrupt nucleocytoplasmic transport through the activity of their leader (l) protein. we have shown that hyperphosphorylation of nuclear pore proteins (nucleoporins or nups), including nup62, nup153, and nup214, is central to this l protein function and requires one or more cytosolic kinases. in this study, potential cellular enzymes involved in encephalomyocarditis virus (emcv) l-directed nup phosphorylation were screened with a panel of specific, cell-permeating kinase inhibitors ...201020881039
polypyrimidine tract-binding protein stimulates the poliovirus ires by modulating eif4g binding.tethered hydroxyl-radical probing has been used to determine the orientation of binding of polypyrimidine tract-binding protein (ptb) to the poliovirus type 1 (mahoney) (pv-1(m)) internal ribosome entry site/segment (ires)-the question of which rna-binding domain (rbd) binds to which sites on the ires. the results show that under conditions in which ptb strongly stimulates ires activity, a single ptb is binding to the ires, a finding which was confirmed by mass spectrometry of ptb/ires complexes ...201020859255
antiviral activity of bignoniaceae species occurring in the state of minas gerais (brazil): part 1.to evaluate the antiviral activity of bignoniaceae species occurring in the state of minas gerais, brazil.201020840554
sumoylation promotes pml degradation during encephalomyocarditis virus infection.the promyelocytic leukemia (pml) protein is expressed in the diffuse nuclear fraction of the nucleoplasm and in matrix-associated structures, known as nuclear bodies (nbs). pml nb formation requires the covalent modification of pml to sumo. the noncovalent interactions of sumo with pml based on the identification of a sumo-interacting motif within pml seem to be required for further recruitment within pml nbs of sumoylated proteins. rna viruses whose replication takes place in the cytoplasm and ...201020826694
synthesis of double-layered rotavirus-like particles using internal ribosome entry site vector system in stably-transformed drosophila melanogaster.we established a bicistronic expression system using an encephalomyocarditis virus (emcv)-derived internal ribosomal entry site (ires) element to generate stably transformed drosophila melanogaster schneider 2 (s2) cells expressing human rotavirus wa capsid proteins, vp2 and vp6, for the synthesis of vp2/6 double-layered virus-like particle (dvlp). the emcv-derived ires permitted bicistronic translation of recombinant vp6. recombinant vp2 and vp6 were detected in extracellular fractions of stabl ...201120820877
generation of stable cell lines expressing gfp-tubulin and photoactivatable-gfp-tubulin and characterization of clones.a bicistronic expression vector can be used to generate stable cell lines expressing green fluorescent protein (gfp)-tubulin and photoactivatable (pa)-gfp-tubulin. this vector, pires (originally available from bd biosciences/clontech), expresses the gene of interest (gfp-tubulin) and a selection marker from the same promoter. the vector uses an internal ribosome entry site (ires) derived from the encephalomyocarditis virus and translates two open-reading frames from one mrna. the gene of interes ...201020810628
role of substance p in viral myocarditis in mice.substance p (sp) is widely expressed in the central nervous system and in peripheral tissues such as myocardial nerves. we examined sp in viral myocarditis in mice induced by encephalomyocarditis virus (emcv). localization of sp in the hearts was examined immunohistochemically, and concentrations of sp in hearts and sera were measured by enzyme immunoassay. substance p levels and density of sp-containing cells in murine hearts on day 6 after emcv inoculation were decreased compared with those in ...201020676845
translation driven by picornavirus ires is hampered from sindbis virus replicons: rescue by poliovirus 2a protease.alphavirus replicons are very useful for analyzing different aspects of viral molecular biology. they are also useful tools in the development of new vaccines and highly efficient expression of heterologous genes. we have investigated the translatability of sindbis virus (sv) subgenomic mrna bearing different 5'-untranslated regions, including several viral internal ribosome entry sites (iress) from picornaviruses, hepatitis c virus, and cricket paralysis virus. our findings indicate that all th ...201020643140
efficacy and safety of a modified vaccinia ankara (mva) vectored plague vaccine in mice.the efficacy and safety of plague vaccines based on the modified vaccinia ankara (mva) viral vector was evaluated. mva recombinants were constructed expressing yersinia pestis antigens under the translational control of the encephalomyocarditis virus (emcv) internal ribosomal entry site (ires) and/or fused to the tissue plasminogen activator (tpa) secretory signal. a mva/y. pestis recombinant that expressed a truncated version of the low-calcium response v antigen (mva/ires/tpa/v(307)), conferre ...201020638759
inhibition of encephalomyocarditis virus and poliovirus replication by quinacrine: implications for the design and discovery of novel antiviral drugs.the 9-aminoacridine (9aa) derivative quinacrine (qc) has a long history of safe human use as an antiprotozoal and antirheumatic agent. qc intercalates into dna and rna and can inhibit dna replication, rna transcription, and protein synthesis. the extent of qc intercalation into rna depends on the complexity of its secondary and tertiary structure. internal ribosome entry sites (iress) that are required for initiation of translation of some viral and cellular mrnas typically have complex structur ...201020631142
oncolytic targeting of renal cell carcinoma via encephalomyocarditis virus.apoptosis is a fundamental host defence mechanism against invading microbes. inactivation of nf-kappab attenuates encephalomyocarditis virus (emcv) virulence by triggering rapid apoptosis of infected cells, thereby pre-emptively limiting viral replication. recent evidence has shown that hypoxia-inducible factor (hif) increases nf-kappab-mediated anti-apoptotic response in clear-cell renal cell carcinoma (ccrcc) that commonly exhibit hyperactivation of hif due to the loss of its principal negativ ...201020623734
[the interferon-induced and antiviral activities of dipeptides].five phosphodipeptides were synthesized; two of them (h-lys-ala(p) and h-pro-ala(p) had interferon-induced activity. these dipeptides at millimolar concentrations (10(-4)) and 10(-5) m) induced the synthesis of late (40-hour) interferon in human peripheral blood lymphocytes. the dipeptides h-lys-ala(p) and h-pro-ala(p) showed a protective antiviral activity in in vivo studies when singly intraperitoneally administered to mice 2 hours before inoculation with murine encephalomyocarditis virus.201020608081
experimental encephalomyocarditis virus infection in small laboratory rodents.encephalomyocarditis virus (emcv) is a cardiovirus that belongs to the family picornaviridae. emcv is an important cause of acute myocarditis in piglets and of fetal death or abortion in pregnant sows. small rodents, especially rats, have been suspected to be reservoir hosts or carriers. this virus also induces type 1 diabetes mellitus, encephalomyelitis, myocarditis, orchitis and/or sialodacryoadenitis in small laboratory rodents. this paper reviews the pathology and pathogenesis of experimenta ...201120594559
the effects of a pparalpha agonist on myocardial damage in obese diabetic mice with heart failure.recent studies have confirmed that pparalpha agonists have not brought the anticipated benefits to patients with type 2 diabetes and potentially fatal heart disease. we hypothesized that such agonists may have a cardio-suppressive effect in treating such disorders, therefore, we inoculated diabetic kkay mice with encephalomyocarditis virus (emcv) to induce a diabetic model with severe myocardial damage. wy14643, a potent pparalpha agonist, was administered intraperitoneally either simultaneously ...201020558911
exacerbation of acute viral myocarditis by tobacco smoke is associated with increased viral load and cardiac apoptosis.exposure to tobacco smoke is known to have deleterious cardiovascular effects. in this study, we tested whether exposure to tobacco smoke exacerbates the severity of viral myocarditis in mice. viral myocarditis was generated in 4-week-old male balb/c mice by injection of encephalomyocarditis virus (emcv). four groups were studied: (1) control (c, no smoke and no virus); (2) smoke only (s, exposure to cigarette smoke for 90 min/day for 15 days); (3) virus only (v); and (4) exposure to smoke for 5 ...201020555426
enhancement of antiviral immunity by small molecule antagonist of suppressor of cytokine signaling.suppressors of cytokine signaling (socss) are negative regulators of both innate and adaptive immunity via inhibition of signaling by cytokines such as type i and type ii ifns. we have developed a small peptide antagonist of socs-1 that corresponds to the activation loop of jak2. socs-1 inhibits both type i and type ii ifn activities by binding to the kinase activation loop via the kinase inhibitory region of the socs. the antagonist, pjak2(1001-1013), inhibited the replication of vaccinia virus ...201020543109
antiviral properties of structural fragments of the peptide selank. 201020506839
src family kinases participate in the regulation of encephalomyocarditis virus-induced cyclooxygenase-2 expression by macrophages.src family kinases (sfks) are non-receptor tyrosine kinases that have been implicated as regulators of the inflammatory response. in this study, the role of sfk activation in the inflammatory response of macrophages to encephalomyocarditis virus (emcv) infection was examined. virus infection of macrophages stimulates the expression of cyclooxygenase-2 (cox-2), interleukin (il)-1beta and inducible nitric oxide synthase (inos). inhibition of sfk attenuates emcv-induced cox-2 expression and prostag ...201020505008
hepatitis c virus controls interferon production through pkr activation.hepatitis c virus is a poor inducer of interferon (ifn), although its structured viral rna can bind the rna helicase rig-i, and activate the ifn-induction pathway. low ifn induction has been attributed to hcv ns3/4a protease-mediated cleavage of the mitochondria-adapter mavs. here, we have investigated the early events of ifn induction upon hcv infection, using the cell-cultured hcv jfh1 strain and the new hcv-permissive hepatoma-derived huh7.25.cd81 cell subclone. these cells depend on ectopic ...201020485506
[sequencing and analysis of the complete genome of encephalomyocarditis virus strain gxlc isolated from swine].the complete genome of encephalomyocarditis virus (emcv)strain gxlc isolated from swine was sequenced and analyzed. five overlapped gene fragments covering the entire open reading frame (orf) were amplified by rt-pcr, and the 3'-untranslated region (utr) and 5'-utr were amplified by the 3'-rapid amplification of cdna ends (race) and 5'-race method, respectively. the genome sequences of strain gxlc were obtained by assembling the sequences of rt-pcr-generated cdna fragments. the length of the com ...201020480643
protein kinase r contributes to immunity against specific viruses by regulating interferon mrna integrity.cytosolic viral rna recognition by the helicases rig-i and mda5 is considered the major pathway for ifn-alpha/beta induction in response to rna viruses. however, other cytoplasmic rna sensors, including the double-stranded rna-binding protein kinase r (pkr), have been implicated in ifn-alpha/beta production, although their relative contribution and mechanism have been unclear. using cells expressing nonfunctional pkr or reduced levels of kinase, we show that pkr is required for production of ifn ...201020478537
immune responses and expression of the virus-like particle antigen of the porcine encephalomyocarditis virus.virus-like particles (vlps) are particles that consist of viral capsid proteins and are structurally similar to authentic virus. to express vlps of the porcine encephalomyocarditis virus (emcv) and investigate their efficacy and immuno response in vivo, a plasmid (p12a3c-pci) containing the p12a and 3c genes of the emcv-k3 viral strain was constructed. the vlps of emcv-k3 were successfully assembled in 293ft cells on 3 days after transfection with p12a3c-pci and were identified as particles of a ...201020378136
phosphatidylinositol 3-kinase regulates macrophage responses to double-stranded rna and encephalomyocarditis virus.virus infection of macrophages stimulates the expression of proinflammatory and antiviral genes interleukin-1 (il-1), inducible nitric oxide synthase (inos) and cyclooxygenase-2 (cox-2). in this study, we show that phosphatidylinositol 3-kinase (pi3k) is required for the inflammatory response of macrophages to virus infection. when macrophages are infected with encephalomyocarditis virus (emcv) there is a rapid and transient activation of pi3k and phosphorylation of its downstream target akt. in ...200920375625
rats as indicators of the presence and dispersal of pathogens in cyprus: ectoparasites, parasitic helminths, enteric bacteria, and encephalomyocarditis virus.rodents play an active role in the transmission of a number of zoonoses by harboring and disseminating the pathogens involved, either through their biological materials or via their ectoparasites. hence, the spatial and seasonal distribution of potential agents of zoonoses may be studied by examining their distribution in the rodent vectors and their ectoparasites. a surveillance was conducted in wild rodents in 51 different areas of cyprus, an island ecosystem, to monitor the reemergence of ech ...201020370433
effects of free immunoglobulin light chains on viral myocarditis.in recent work, we have demonstrated a crucial role of mast cells in the development of viral myocarditis. viral infection could lead to increased synthesis of free immunoglobulin light chains (flc) and our earlier work showed that flc can trigger mast cell activation.201020360247
evidence for translational regulation by the herpes simplex virus virion host shutoff protein.the herpes simplex virus (hsv) virion host shutoff protein (vhs) encoded by gene ul41 is an mrna-specific rnase that triggers accelerated degradation of host and viral mrnas in infected cells. we report here that vhs is also able to modulate reporter gene expression without greatly altering the levels of the target mrna in transient-transfection assays conducted in hela cells. we monitored the effects of vhs on a panel of bicistronic reporter constructs bearing a variety of internal ribosome ent ...201020357089
encephalomyocarditis virus infection in an italian zoo.a fatal encephalomyocarditis virus (emcv) infection epidemic involving fifteen primates occurred between october 2006 and february 2007 at the natura viva zoo. this large open-field zoo park located near lake garda in northern italy hosts one thousand animals belonging to one hundred and fifty different species, including various lemur species. this lemur collection is the most relevant and rich in italy. a second outbreak between september and november 2008 involved three lemurs. in all cases, ...201020298561
antiviral activity of solanum paniculatum extract and constituents.solanum species are traditionally employed as antiherpes and anticancer agents in different countries. s. paniculatum has widespread ethnomedical uses in brazil, including the treatment of viral infections. this paper reports on the isolation of neotigogenin (1) and the new compound delta25(27)-tigogenin-3-o-beta-d-glucopyranoside (2), obtained as a mixture of r and s diastereoisomers at c22 from an ethanol extract of s. paniculatum leaves, along with the determination of their cytotoxicity agai ...200920158151
plakophilin 1 stimulates translation by promoting eif4a1 activity.plakophilins 1-3 (pkp1-3) are desmosomal proteins of the p120(ctn) family of armadillo-related proteins that are essential for organizing the desmosomal plaque. recent findings identified pkps in stress granules, suggesting an association with the translational machinery. however, a role of pkps in controlling translation remained elusive so far. in this study, we show a direct association of pkp1 with the eukaryotic translation initiation factor 4a1 (eif4a1). pkp1 stimulated eif4a1-dependent tr ...201020156963
lgp2: positive about viral sensing. 201020133887
seroprevalence of encephalomyocarditis virus in intensive pig farms in china. 201020118474
difference in susceptibility to mxa protein between a coxsackievirus b1 isolate and prototype, impact of serial cell culture passage.human enteroviruses (evs) cause a broad spectrum of acute and chronic diseases including meningitis and myocarditis. the type i interferon-induced mxa protein has been shown to inhibit the replication of an ev, coxsackievirus b4 (cvb4), but not cardioviruses such as encephalomyocarditis virus and mengo virus, members of the picornaviridae family. evs consist of more than 60 distinct serotypes against which the antiviral activity of mxa was not investigated yet. the main aim of this study was to ...201020087945
lgp2 is a positive regulator of rig-i- and mda5-mediated antiviral responses.rna virus infection is recognized by retinoic acid-inducible gene (rig)-i-like receptors (rlrs), rig-i, and melanoma differentiation-associated gene 5 (mda5) in the cytoplasm. rlrs are comprised of n-terminal caspase-recruitment domains (cards) and a dexd/h-box helicase domain. the third member of the rlr family, lgp2, lacks any cards and was originally identified as a negative regulator of rlr signaling. in the present study, we generated mice lacking lgp2 and found that lgp2 was required for r ...201020080593
influence of the hepatitis c virus 3'-untranslated region on ires-dependent and cap-dependent translation initiation.translation of hepatitis c virus (hcv) genomic rna is directed by an internal ribosome entry site (ires) in the 5'-untranslated region (5'-utr), and the hcv 3'-utr enhances ires activity. since the hcv 3'-utr has a unique structure among 3'-utrs, we checked possible communication between the 5'- and the 3'-utr of hcv during translation using chimeric reporter rnas. we show that translation directed by the hcv ires and by the hcv-like ires of porcine teschovirus (ptv) which belongs to a quite dis ...201020079737
cytosolic rna recognition pathway activates 14-3-3 protein mediated signaling and caspase-dependent disruption of cytokeratin network in human keratinocytes.the skin is the primary boundary between the body and the environment. in addition to its properties as a physical barrier, skin keratinocytes actively participate in many defense mechanisms. viral double-stranded rna (dsrna) is the most important viral structure involved in activation of immune response. intracellular detection of dsrna by cytoplasmic receptors activates well-characterized antiviral response, as well as pro-inflammatory response and apoptosis of virus-infected cells. here, we h ...201020070120
factors modifying host resistance to virus infection: ii. enhanced susceptibility of mice to encephalomyocarditis virus infection during pregnancy. 196819971047
immunostimulatory rna blocks suppression by regulatory t cells.the role of immune suppression by regulatory t (treg) cells in the maintenance of immune homeostasis is well established. however, little is known about how treg cell function is inhibited on viral infection to allow the development of a protective immune response. as viral rna is a crucial mediator for activation of antiviral immunity, we examined the effects of immunostimulatory rna and infection with rna viruses on treg cell function. we show that synthetic rna oligonucleotides potently inhib ...201019966212
hiv- 1 protease inhibits cap- and poly(a)-dependent translation upon eif4gi and pabp cleavage.a number of viral proteases are able to cleave translation initiation factors leading to the inhibition of cellular translation. this is the case of human immunodeficiency virus type 1 protease (hiv-1 pr), which hydrolyzes eif4gi and poly(a)-binding protein (pabp). here, the effect of hiv-1 pr on cellular and viral protein synthesis has been examined using cell-free systems. hiv-1 pr strongly hampers translation of pre-existing capped luc mrnas, particularly when these mrnas contain a poly(a) ta ...200919956697
direct cd1d-mediated stimulation of apc il-12 production and protective immune response to virus infection in vivo.cd1d-restricted nkt cells rapidly stimulate innate and adaptive immunity through production of th1 and/or th2 cytokines and induction of cd1d(+) apc maturation. however, therapeutic exploitation of nkt cells has been hampered by their paucity and defects in human disease. nkt cell-apc interactions can be modeled by direct stimulation of human apcs through cd1d in vitro. we have now found that direct ligation with multiple cd1d mabs also stimulated bioactive il-12 release from cd1d(+) but not cd1 ...201019949077
Refresh
firstprev
12345678910...
nextlast
Displaying items 201 - 300 of 2665