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comparative effects of losartan, captopril, and enalapril on murine acute myocarditis due to encephalomyocarditis virus.losartan, a recently developed nonpeptide angiotensin ii (aii) receptor antagonist, was orally administered for 14 days to mice with viral myocarditis, beginning 7 days after encephalomyocarditis virus inoculation. the angiotensin-converting enzyme inhibitors (acei) captopril and enalapril were also administered in the same manner to compare the therapeutic effects of these three drugs on the degree of myocarditis, acute heart failure, and left ventricular (lv) hypertrophy. heart weight and the ...19957564367
involvement of the double-stranded-rna-dependent kinase pkr in interferon expression and interferon-mediated antiviral activity.the signaling mechanisms responsible for the induced expression of interferon (ifn) genes by viral infection or double-stranded rna (dsrna) are not well understood. here we investigate the role of the interferon-induced dsrna-dependent protein kinase pkr in the regulation of ifn induction. biological activities attributed to pkr include regulating protein synthesis, mediating ifn actions, and functioning as a possible tumor suppressor. since binding of dsrna is required for its activation, pkr h ...19957568028
retroviral coexpression of a multidrug resistance gene (mdr1) and human alpha-galactosidase a for gene therapy of fabry disease.human alpha-galactosidase a (alpha-gal a; ec.3.2.1.22) is a lysosomal exoglycosidase encoded by a gene on xq22. deficiencies of this enzyme result in fabry disease, an x-chromosome-linked recessive disorder that leads to premature death in affected males. for treatment of genetic diseases, we have developed a retroviral vector system, psxlc/pha, that enables coexpression of drug-selectable markers with a second nonselectable gene as part of a bicistronic message using the promoter from the harve ...19957578409
m7gpppg cap dependence for efficient translation of drosophila 70-kda heat-shock-protein (hsp70) mrna.to investigate whether preferential translation of the heat-shock mrnas occurs via cap-independent translation, the requirement for the m7gpppg cap structure for efficient translation of 70-kda heat-shock-protein (hsp70) mrna was quantified by in vitro translation and by in vivo translation following electroporation. hsp70 mrna was transcribed in vitro with and without a cap structure. translation in the rabbit reticulocyte or wheat germ lysate was reduced about 70% when the cap was absent. for ...19957588716
phage rna polymerase vectors that allow efficient gene expression in both prokaryotic and eukaryotic cells.we have developed expression vectors that direct the synthesis of proteins from a common set of signals in both prokaryotic and eukaryotic cells. to allow transcription from a common promoter the vectors rely upon a phage rna polymerase (rnap). to direct initiation of translation to the same start codon the vectors utilize an internal ribosome entry site (ires) from encephalomyocarditis virus (emcv) that has been modified to include a prokaryotic ribosome-binding site (rbs) at an appropriate dis ...19957590325
cloning and expression of the vp1 major capsid protein of diabetogenic encephalomyocarditis (emc) virus and prevention of emc virus-induced diabetes by immunization with the recombinant vp1 protein.the development of diabetes in mice induced by encephalomyocarditis (emc) virus provides the best experimental evidence that viruses have an aetiological role in the pathogenesis of this disease. the major capsid protein (vp1) of emc virus is important for both the attachment of the virus to pancreatic beta cells and for the determination of antigenicity. this experiment was initiated to clone the gene for the major capsid protein, vp1, of the diabetogenic emc (emc-d) virus, express the vp1 prot ...19957595359
iodine-mediated inactivation of lipid- and nonlipid-enveloped viruses in human antithrombin iii concentrate.human plasma-derived protein concentrates intended for clinical use must be treated for viral inactivation to ensure patient safety. this study explored the use of liquid iodine for inactivation of several lipid- and nonlipid-enveloped viruses in an antithrombin iii (at-iii) concentrate. iodine at levels of 0.01% to 0.02% caused between 43% and 94% loss of at-iii activity, as well as degradation of at-iii as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (sds-page) and wester ...19957606009
picornavirus-specific cd4+ t lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies.picornaviruses are a family of positive-strand rna viruses that are responsible for a variety of devastating human and animal diseases. an attenuated strain of mengovirus (vmc24) is serologically indistinguishable from the lethal murine wild-type mengovirus and encephalomyocarditis virus (emcv). immunogen-specific stimulation of vmc24-immune splenocytes in vitro demonstrates preferential activation of cd4+ lymphocytes. vmc24-immune splenocytes adoptively transferred to naive recipients conferred ...19957609060
effect of combination therapy with ok432 and recombinant human interferon-alpha a/d on atrial natriuretic peptide gene expression in mice with viral myocarditis.the effects of combination therapy with the immunomodulators ok432 (derived from the su strain of streptococcus pyogenes a3; 1 unit corresponds to 0.1 mg of dried streptococci dissolved in 0.1 ml of saline) and human recombinant interferon-alpha a/d (ifn) on cardiac atrial natriuretic peptide (anp) gene expression and myocardial hypertrophy were examined in a murine model of viral myocarditis with congestive heart failure. therapy was started 24 h after inoculation with encephalomyocarditis viru ...19957616436
stringent chemical and thermal regulation of recombinant gene expression by vaccinia virus vectors in mammalian cells.we developed a stringently regulated expression system for mammalian cells that uses (i) the rna polymerase, phi 10 promoter, and t phi transcriptional terminator of bacteriophage t7; (ii) the lac repressor, lac operator, rho-independent transcriptional terminators and the gpt gene of escherichia coli; (iii) the rna translational enhancer of encephalomyocarditis virus; and (iv) the genetic background of vaccinia virus. in cells infected with the recombinant vaccinia virus, reporter beta-galactos ...19957624318
poliovirus protease 3c mediates cleavage of microtubule-associated protein 4.poliovirus infection results in a number of host cell changes, including specific alterations in cellular proteins. this study further characterizes the cleavage of a cytoskeletal protein, microtubule-associated protein 4 (map-4) and investigates the identity of the viral protease which mediates its cleavage. map-4 cleavage by poliovirus was previously identified using a monoclonal antibody (m. joachims and d. etchison, 1992, j. virol. 66, 5997-5804). in this study, map-4 cleavage was found to o ...19957645249
the role of interferon beta in human cytomegalovirus-mediated inhibition of hla dr induction on endothelial cells.human cytomegalovirus (hcmv), a member of the virus family herpesviridae that is associated with extensive worldwide morbidity and mortality in immunocompromised hosts, inhibits interferon-gamma (ifn gamma)-mediated induction of human leukocyte antigen (hla) class ii antigens on endothelial cells. in this study, the ability of hcmv-infected endothelial cells to synthesize interferon-beta (ifn beta), and the role of ifn beta in hcmv-mediated inhibition of hla class ii induction, was investigated. ...19957646336
cloning and characterization of a rnase l inhibitor. a new component of the interferon-regulated 2-5a pathway.the 2-5a/rnase l system is considered as a central pathway of interferon (ifn) action and could possibly play a more general physiological role as for instance in the regulation of rna stability in mammalian cells. we describe here the expression cloning and initial characterization of rli (for rnase l inhibitor), a new type of endoribonuclease inhibitor. rli cdna codes for a 68-kda polypeptide whose expression is not regulated by ifn. its expression in reticulocyte extracts antagonizes the 2-5a ...19957539425
synergistic effects of tacrolimus and human interferon-alpha a/d in murine viral myocarditis.the effects of interferon-alpha a/d (ifn) therapy in combination with various immunosuppressants were investigated in a murine model of viral myocarditis. viral infection is an important cause of morbidity in immunocompromised hosts and transplant recipients. human ifn therapy reduces viral replication, reducing the virus-induced myocardial destruction. groups consisting of 25 c3h/he mice received i.p. injections of prednisolone, azathioprine, 15-deoxyspergualin, cyclosporine or tacrolimus (fk50 ...19957542339
hemin inhibits the interferon-beta-induced antiviral state in established cell lines.hemin and other metalloporphyrins are known as very versatile compounds in nature, because they are able to carry out numerous functions in a free state or in association with specific proteins. when friend murine erythroleukemia cells are treated with ifn-beta plus 100 microm hemin, the antiviral state is not observed, whereas the antiviral effect of ifn-gamma is unaffected by hemin treatment. this inhibitory effect of hemin is not restricted to erythroid cells. in fact, it is also observed in ...19957544231
high avidity ifn-neutralizing antibodies in pharmaceutically prepared human igg.this paper demonstrates and characterizes naturally occurring antibodies to interferon (ifn) in human igg preparations. in vitro neutralization of the antiviral effect of ifn alpha and ifn beta, but not ifn gamma, was observed in 12 of 15 normal igg preparations. the neutralizing capacity was higher against rifn alpha 2a and rifn alpha 2c than against lymphoblastoid ifn alpha and ifn beta. frühsommer meningoencephalitis hyperimmune igg and hepatitis-b hyperimmune igg showed potent neutralization ...19957738163
chronic effect of losartan in a murine model of dilated cardiomyopathy: comparison with captopril.the long-term effects of losartan, an angiotensin ii subtype-i receptor antagonist, were compared with those of captopril in a murine model of dilated cardiomyopathy caused by encephalomyocarditis virus. four weeks after viral inoculation, 42 dba/2 mice were given oral losartan 1.2 mg/kg/day (n = 8), 12 mg/kg/day (n = 8) or 60 mg/kg/day (n = 8) or captopril 7.5 mg/kg/day (n = 8) in drinking water or distilled water (n = 10). mice were killed at the end of the 12-wk treatment period. heart weight ...19957752100
early development of encephalomyocarditis (emc) virus-induced orchitis in syrian hamsters.lesions associated with encephalomyocarditis (emc) virus in the testes of syrian hamsters were investigated. histopathologic changes were first detectable by light microscopy at 3 days postinoculation (dpi). immunohistochemically, virus antigens were detected in the cytoplasm of germ cells and sertoli cells in some seminiferous tubules beginning at 2 dpi. the following ultrastructural changes were observed: 1) swelling of mitochondria and dilatation of endoplasmic reticulum in germ cells, 2) lar ...19957771059
targeted disruption of the p50 subunit of nf-kappa b leads to multifocal defects in immune responses.nf-kappa b, a heterodimeric transcription factor composed of p50 and p65 subunits, can be activated in many cell types and is thought to regulate a wide variety of genes involved in immune function and development. mice lacking the p50 subunit of nf-kappa b show no developmental abnormalities, but exhibit multifocal defects in immune responses involving b lymphocytes and nonspecific responses to infection. b cells do not proliferate in response to bacterial lipopolysaccharide and are defective i ...19957834752
encephalomyocarditis viruses with short poly(c) tracts are more virulent than their mengovirus counterparts.we have constructed three cdna clones of encephalomyocarditis virus strain r (emcv-r) with poly(c) tracts of c4, c9, and c20. rna transcribed from these cdnas was infectious to hela cells, and the resultant viruses grew well in this system, albeit with plaque sizes that were proportional to the poly(c) length. when injected into mice, the progeny viruses were only slightly less pathogenic than emcv-r, and the observed degree of attenuation was not nearly as dramatic as for equivalent mengoviruse ...19957884926
localization of binding site for encephalomyocarditis virus rna polymerase in the 3'-noncoding region of the viral rna.we previously showed that encephalomyocarditis (emc) virus rna-dependent rna polymerase (3dpol) binds specifically to 3'-terminal segments of emc virus rna. this binding, which depends on both the 3'-noncoding region (3'-ncr) and 3'-poly (a) tail [together denoted 3'-ncr(a)], may be an important step in the initiation of virus replication. in this paper, the 3'-ncr and 3'-poly(a) were separately transcribed then mixed, but no complex with 3dpol was obtained, showing that covalent attachment of t ...19957885833
detection of reverse transcriptase by a highly sensitive assay in sera from persons infected with human immunodeficiency virus type 1.in an ultrasensitive assay for reverse transcriptase (rt), an in vitro-transcribed heteropolymeric rna sequence was used as a template and polymerase chain reaction (pcr) amplification with southern blot hybridization served as a detection system for the cdna reaction product. the assay, called amp-rt, detected 9 tested retroviruses in unconcentrated culture supernatants diluted 10(2)- to 10(5)-fold. a comparative analysis using human immunodeficiency virus type 1 (hiv-1) revealed that amp-rt wa ...19957538549
translation of encephalomyocarditis virus rna by internal ribosomal entry.picornavirus 5' ncrs contain ires elements that have been divided into two groups, exemplified by pv (type 1) and emcv (type 2). these elements are functionally related and have an intriguing level of structural and sequence similarity. some conserved rna sequences and/or structures may correspond to cis-acting elements involved in ires function, so that there may also be similarities in the mechanism by which the two types or ires promote initiation. the function of both types of ires element a ...19957555090
characterization of insulin-dependent diabetes mellitus induced by a new variant (dk-27) of encephalomyocarditis virus in dba/2 mice.a murine diabetes mellitus induced with a new diabetogenic variant (dk-27) which we isolated from the m variant of the encephalomyocarditis (emc) virus was characterized. male dba/2 mice (9.5 weeks old) were infected with various infectious doses of dk-27 intraperitoneally. blood glucose and insulin levels were examined in association with the viral replication. pancreatic pathology and hormone contents and stable hemoglobin a1c (st-a1c) levels were also examined on the final day of observation ...19957556422
[relation between structure and anti-viral activity in interferon system].the interferons (ifn) were discovered in 1957 as biological agents interfering with viral replication. ifns were initially classified according to their sources as leukocyte, fibroblast and immune ifns. both leukocyte and fibroblast ifns are designated as type i ifns and immune ifn as a type ii ifn. there are almost twenty related ifns which belong to the group of type i ifn. ifn-alpha 2 and ifn-omega 1 are described as members of the large group of type i ifn. both natural ifn-alpha 2 and ifn-o ...19957595866
initiation of protein synthesis by the eukaryotic translational apparatus on circular rnas.the ribosome scanning model predicts that eukaryotic ribosomal 40s subunits enter all messenger rnas at their 5' ends. here, it is reported that eukaryotic ribosomes can initiate translation on circular rnas, but only if the rnas contain internal ribosome entry site elements. long-repeating polypeptide chains were synthesized from rna circles with continuous open reading frames. these results indicate that ribosomes can translate such rna circles for multiple consecutive rounds and that the free ...19957536344
encephalomyocarditis (emc) virus infection in the common vole, microtus arvalis.encephalomyocarditis (emc) virus infection in the common vole was examined for the first time. sixteen 8-week-old males inoculated intraperitoneally with 10(5) plaque-forming units (pfu)/animal of the d variant of emc virus were killed 3 and 7 days after inoculation (3 and 7 dai). viral replication was detected in the brain (10(5) pfu/g), heart (10(4) pfu/g) and pancreas (10(7) pfu/g) of all 8 animals at 3dai. it was found in the pancreas (10(3) pfu/g) of all 8 animals and in the brain (10(4) pf ...19957603005
interaction between the 5'-terminal cloverleaf and 3ab/3cdpro of poliovirus is essential for rna replication.on the basis of sequence alignments and secondary structure comparisons of the first 100 nucleotides of enterovirus and rhinovirus rnas, chimeric constructs in which this region of poliovirus type 1 mahoney [pv1(m)] is replaced with that of human rhinovirus type 2 (hrv2) or hrv14 have been engineered. these chimeric constructs contain the internal ribosomal entry site of either poliovirus or encephalomyocarditis virus. independent of the internal ribosomal entry site elements, only the construct ...19957745714
mutational analysis of the j-k stem-loop region of the encephalomyocarditis virus ires.cap-independent translation of encephalomyocarditis virus (emcv) rna is controlled by a segment of the 5' untranslated region termed the internal ribosomal entry site, or ires. the ires contains a series of stem-loop structural elements. the j and k stems (emcv bases 682 to 795), near the center of the ires, are well conserved among all cardio-, aphtho-, and hepatoviruses. we have examined the biological roles of these elements by constructing mutations within the j-k sequences of emcv and testi ...19957769702
a retrospective serological survey of the encephalomyocarditis virus among pigs in chiba prefecture, japan.one thousand two hundred and forty pigs' sera collected from 1975 to 1992 on 240 farms in chiba prefecture were subjected to a neutralization test for the encephalomyocarditis (emc) virus. seven (23.3%) of 30 pigs in 1975 had neutralizing antibodies against the emc virus. the antibody positive rates each year ranged from 16.7% (1976) to 56.3% (1981). the differences of antibody positive rates between districts were not great after 1985. these serological results suggested that the emc virus infe ...19958519923
defective point mutants of the encephalomyocarditis virus internal ribosome entry site can be complemented in trans.point mutations were introduced at random into cdna corresponding to nucleotides 260-833 of the encephalomyocarditis virus (emcv) 5' noncoding region. this region contains the internal ribosome entry site (ires). the mutations were identified by sequence analysis and the effect on the activity of the ires was determined using in vitro translation reactions in rabbit reticulocyte lysate. significantly defective mutants each contained multiple point mutations. these mutants were constructed into a ...19958525641
direct evidence that polypyrimidine tract binding protein (ptb) is essential for internal initiation of translation of encephalomyocarditis virus rna.the requirement of ptb, polypyrimidine tract binding protein, for internal initiation of translation has been tested using an rna affinity column to deplete rabbit reticulocyte lysates of ptb. the affinity column was prepared by coupling cnbr-activated sepharose with the segment of the 5'-untranslated region of encephalomyocarditis virus (emcv) rna previously shown to bind ptb. lysates passed through this column were devoid of ptb, and were incapable of internal initiation of translation depende ...19958548657
[internal initiation of translation in eukaryotes. chemical probing of the encephalomyocarditis virus rna ires-element in the 48s preinitiation complex].using in vitro t7 polymerase system, the transcript containing the ires-element (nts 315-833), and the initial part of the coding sequence of encephalomyocarditis virus (emcv) rna (nts 834-1155) was prepared. its complex with the 40s ribosomal subunit (48s preinitiation complex) was then isolated by sucrose gradient sedimentation from ascites carcinoma krebs2 cell extracts after preincubation with the transcript. the complex was treated with dimethylsulphate (dms), a common reagent for chemical ...19958552069
differential sensitivities of viruses in red cell suspensions to methylene blue photosensitization.previous studies explored the feasibility of using the photosensitizer methylene blue (mb) as a virucidal agent in red cell suspensions. under treatment conditions (5 microm [5 mumol/l] mb, 3.4 x 10(4) j/m2) that resulted in more than 6 log10 inactivation of vesicular stomatitis virus (vsv) or of the enveloped bacteriophage phi 6, red cell membrane alterations were observed. increased red cell ion permeability and the binding of plasma proteins to the red cell surface were the most sensitive ind ...19948023394
the encephalomyocarditis virus 3c protease is a substrate for the ubiquitin-mediated proteolytic system.the encephalomyocarditis virus 3c protease has been shown to be rapidly degraded in infected cells and in vitro in rabbit reticulocyte lysate. the in vitro degradation, at least, is accomplished by a virus-independent, atp-dependent proteolytic system. here we identify this proteolytic system as the ubiquitin-mediated system. incubation of the 3c protease in rabbit reticulocyte or cultured mouse cell lysate preparations, alone or in the presence of added ubiquitin or methylated ubiquitin, result ...19947961784
a search for candidate viruses in type 1 diabetic pancreas using the polymerase chain reaction.in order to investigate a possible viral aetiology for type 1 diabetes the polymerase chain reaction (pcr) technique was used. pancreatic tissue from type 1 diabetic subjects was examined for the presence of a panel of common viruses. primers specific for mumps, measles, cytomegalovirus, and epstein barr virus, as well as primers located in a highly conserved region of the enterovirus genome which are capable of detecting all of the following family members: coxsackie b, echovirus, polio, mengov ...19947955973
an angiotensin ii receptor antagonist reduces myocardial damage in an animal model of myocarditis.recently, an angiotensin-converting enzyme inhibitor was shown to have a beneficial effect on virus-induced myocardial injury. we investigated the effect of a new angiotensin ii type 1 receptor antagonist, (+-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-([2'-(1h-tetrazol-5-yl)biphenyl-4-yl]methyl)-1h-benz imi dazole-7- carboxylate (tcv-116), in an animal model of viral myocarditis induced by encephalomyocarditis virus.19947923693
equal transcription of wild-type and mutant p53 using bicistronic vectors results in the wild-type phenotype.somatic and germ-line mutations of p53 alleles inactivate the function of the protein. it has been suggested that mutant p53 can inactivate the wild-type protein and therefore have a trans-dominant negative effect. to investigate the interaction between wild-type and mutant proteins when both alleles are equally transcribed, we designed bicistronic vectors containing the internal ribosome entry site of the encephalomyocarditis virus and expressing wild-type and mutant p53. analysis of the transc ...19948313374
encephalomyocarditis (emc) virus-induced testicular lesion in balb/c mice.characteristics of encephalomyocarditis (emc) virus-induced testicular lesions were investigated in 4- and 8-week-old balb/c male mice after intraperitoneal (i.p.) and intratesticular (left) (i.t.) inoculation of the d variant of emc virus (emc-d). apart from variation in severity and incidence, the histopathological nature of the resultant testicular lesion was similar in all infected mice, and was characterized by degeneration and necrosis of germinal cells and spermatogonia with inflammatory ...19947830372
dicistronic polioviruses as expression vectors for foreign genes.we have made use of certain novel genetic elements of picornaviruses termed internal ribosomal entry sites (ires) to construct a viral rna with the following genetic order: pv 5' ntr-emcv ires-pv orf-3' ntr (pv, poliovirus; ntr, nontranslated region; emcv, encephalomyocarditis virus; orf, open reading frame). transfection of this rna into hela cells yielded a poliovirus (w1-pnenpo) that contained two heterologous ires elements (type 1 ires of pv; type 2 ires of emcv) in tandem. the insertion of ...19947865334
trans complementation by rna of defective foot-and-mouth disease virus internal ribosome entry site elements.a region of about 435 bases from the 5' noncoding region of foot-and-mouth disease virus rna directs internal initiation of protein synthesis. this region, termed the internal ribosome entry site (ires), is predicted to contain extensive secondary structure. precise deletion of five predicted secondary structure features has been performed. the mutant ires elements have been constructed into vectors which express bicistronic mrnas and assayed within cells. each of the modified ires elements was ...19948289373
expression of hepatitis a virus precursor protein p3 in vivo and in vitro: polyprotein processing of the 3cd cleavage site.hepatitis a virus (hav) cdnas encoding the p3 region proteins were expressed in vivo and in vitro to characterize the hav 3d protein and to identify the cleavage site between 3c and 3d. protein coding sequences were placed under control of a t7 promoter and an emcv translational initiation signal. t7 rna polymerase was provided by simultaneous infection of transfected bs-c-1 cells with a recombinant vaccinia virus vtf7-3 (t. r. fuerst et al., proc. natl. acad. sci. usa 83, 8122-8126, 1986). effi ...19948291234
production of single-stranded dna in mammalian cells by means of a bacterial retron.msdna-ec67, a peculiar multicopy single-stranded dna of a specific sequence was produced in nih3t3 mouse cells. retron-ec67, a retroelement from escherichia coli, was introduced under the t7 polymerase promoter and the non-translated 5'-region of the encephalomyocarditis virus. the construct was then transfected into the nih3t3 cells constitutively producing t7 rna polymerase. forty-eight hours after transfection, msdna-ec67 was detected in the cells by means of southern blot hybridization and r ...19947507924
reproductive failure in sows following experimental infection with a belgian emcv isolate.in this study, a transplacental infection with fetal death was demonstrated following inoculation of pregnant sows with a belgian encephalomyocarditis virus (emcv) isolate. eight multiparus sows were inoculated between 60 and 92 days of gestation with this emcv-isolate to investigate its ability to cause reproductive failure in sows. virus persistence and antibody titre in their offspring were also studied. only the two sows inoculated at 60 days of gestation showed premature farrowing, but all ...19948203116
self-amplifying expression from the t7 promoter in 3t3 mouse fibroblasts.to increase the levels of exogenous or foreign gene expression in mammalian cells, this study sought to develop an 'autogene' that will self-amplify. an autogene plasmid, pt7-g1, containing the t7 phage rna polymerase-encoding modified gene (g1) under control of its cognate t7 promoter, was only obtained when the plasmid contained the encephalomyocarditis (emc) untranslated sequence. in vitro transcription and translation studies confirmed that both the t7 promoter and the g1 gene were completel ...19948206381
the 5'-untranslated regions of picornavirus rnas contain independent functional domains essential for rna replication and translation.the role of the 5'-untranslated region (5'utr) in the replication of enteroviruses has been studied by using a series of poliovirus type 3 (pv3) replicons containing the chloramphenicol acetyltransferase reporter gene in which the 5'utr was replaced by the 5'utr of either coxsackievirus b4 or human rhinovirus 14 or composite 5'utrs derived from sequences of pv3, human rhinovirus 14, coxsackievirus b4, or encephalomyocarditis virus. the results indicate that efficient replication of an enteroviru ...19948207812
persistence of the d variant of encephalomyocarditis virus in the icr-swiss mouse.the d variant of encephalomyocarditis virus (emcv-d) is used in the murine model to study virus-induced, acute-onset diabetes mellitus (iddm) and myocarditis. in this model, viral replication and disease occur within seven days post infection (p.i.), and by day 10 p.i., no infectious virus is detectable. the present study examined the possibility that emcv-d persists in icr-swiss mice after the acute infection is resolved. the data show that viral antigen is detected at 28 days p.i. within the p ...19948108461
polioviruses containing picornavirus type 1 and/or type 2 internal ribosomal entry site elements: genetic hybrids and the expression of a foreign gene.a picornavirus hybrid genome was constructed in which the internal ribosomal entry site (ires) of encephalomyocarditis virus was inserted between the 5' non-translated region and the open reading frame of poliovirus (pv), type 1 (mahoney). upon transfection into hela cells, the hybrid rna replicated and yielded a derivative of pv (w1-pnenpo). the pv ires could be removed from ppnenpo, which resulted in a hybrid picornavirus (w1-p108enpo) in which the translation of the pv open reading frame norm ...19947509072
physiochemical and immunological characterization of hepatitis a virus nucleocapsids expressed in a vaccinia virus/t7/emcv system.expression of the entire open reading frame of hepatitis a virus was achieved in a vaccinia virus/t7/emcv hybrid system. the expressed antigens were characterized as particles with buoyant densities and sedimentation coefficients typical of empty capsids and pentamers of hav. this was further confirmed by electron microscopy. all capsid proteins were determined as components of the particles which raised neutralizing antibodies in an immunized rabbit.19947979980
involvement of the irf-1 transcription factor in antiviral responses to interferons.the mechanisms underlying interferon (ifn)-induced antiviral states are not well understood. interferon regulatory factor-1 (irf-1) is an ifn-inducible transcriptional activator, whereas irf-2 suppresses irf-1 action. the inhibition of encephalomyocarditis virus (emcv) replication by ifn-alpha and especially by ifn-gamma was impaired in cells from mice with a null mutation in the irf-1 gene (irf-1-/- mice). the irf-1-/- mice were less resistant than normal mice to emcv infection, as revealed by ...19948009222
radiation inactivation of human gamma-interferon: cellular activation requires two dimers.gamma-interferon (ifn-gamma) is a 17-kda broad-spectrum cytokine which exerts its effects on a variety of target cells through its interaction with the ifn-gamma receptor. although physicochemical studies of escherichia coli-derived ifn-gamma, as well as its crystal structure, demonstrate that it is a homodimer in solution (m(r) 34,000), previous radiation inactivation studies yielded a functional size for ifn-gamma of 63-73 kda in an antiviral assay. to understand the relationship between the s ...19948016072
expression of a functional human type i interferon receptor in hamster cells: application of functional yeast artificial chromosome (yac) screening.the previously cloned human interferon alpha/beta (hu-ifn-alpha/beta; type i interferon) receptor cdna appears to be only one component of a receptor complex since expression of the cdna in mouse cells confers sensitivity only to hu-ifn-alpha b2, but a monoclonal antibody against this cloned receptor subunit inhibits biological activities of hu-ifn-alpha a, hu-ifn-alpha b2, hu-ifn-omega, and hu-ifn-beta. here we report that a yeast artificial chromosome (yac) containing a segment of human chromo ...19948027072
myocardial beta-receptor and cardiac angiotensin alterations during the acute and chronic phases of viral myocarditis.recovery from viral myocarditis is usually excellent and complete although it occasionally results in sudden death during its acute stage. while neurohormonal mechanisms play an important role in the adaptation to heart diseases, little is known about the alteration of the neurohormonal system in viral myocarditis. therefore, we examined the myocardial beta-adrenergic receptor and cardiac angiotensin i and ii concentrations in a murine model of viral myocarditis induced by an encephalomyocarditi ...19948056011
treatment of virus-induced myocardial injury with a novel immunomodulating agent, vesnarinone. suppression of natural killer cell activity and tumor necrosis factor-alpha production.controversy still exists concerning the therapy for viral myocarditis which manifests a wide variety of clinical symptoms. vesnarinone, a quinolinone derivative that was developed as a positive inotropic agent with complex actions, including phosphodiesterase inhibition and cation channel modification, has recently been confirmed to improve the prognosis of patients with chronic heart failure. however, the precise mechanism of this beneficial effect is not yet clearly understood. in this study, ...19948083362
sublocalization of the human interferon-gamma receptor accessory factor gene and characterization of accessory factor activity by yeast artificial chromosomal fragmentation.a chromosomal fragmentation procedure was employed to produce a deletion set of yeast artificial chromosomes (yacs) from a parental yac, gart d142h8, known to map to human chromosome 21q and to encode the human interferon-gamma receptor (hu-ifn-gamma r) accessory factor gene as well as the phosphoribosylglycinamide formyltransferase (gart) gene. when expressed in chinese hamster ovary cells, these deleted yacs retain accessory factor activity, as judged by major histocompatibility complex class ...19948120065
identification and sequence of an accessory factor required for activation of the human interferon gamma receptor.human chromosomes 6 and 21 are both necessary to confer sensitivity to human interferon gamma (hu-ifn-gamma), as measured by induction of class i human leukocyte antigen (hla) and protection against encephalomyocarditis virus (emcv) infection. whereas human chromosome 6 encodes the hu-ifn-gamma receptor, human chromosome 21 encodes accessory factors for generating biological activity through the hu-ifn-gamma receptor. probes from a genomic clone were used to identity cdna clones expressing a spe ...19948124716
encephalomyocarditis virus internal ribosomal entry site rna-protein interactions.translational initiation of encephalomyocarditis virus (emcv) mrna occurs by ribosomal entry into the 5' nontranslated region of the emcv mrna, rather than by ribosomal scanning. internal ribosomal binding requires a cis-acting element termed the internal ribosomal entry site (ires). ires elements have been proposed to be involved in the translation of picornavirus mrnas and some cellular mrnas. internal ribosome binding likely requires the interaction of trans-acting factors that recognize both ...19948151781
characterization of nuclear factors involved in 202 gene induction by ifn-alpha, viruses or dsrna in murine leukemia cells.when treated with ifn-alpha, l1210 leukemia cells express high levels of the mouse 202 gene mrna after a few hours. three tandem copies of a 43 bp fragment (gabox) homologous to the ifn-stimulatable response element (isre), located in the 5'-flanking region of the 202 gene, were linked to the reporter cat gene and transiently transfected into l1210 cells. the data suggest that the ga box is sufficient to confer transcriptional inducibility upon ifn stimulation. binding assays, using the labeled ...19947861982
efficient expression of drug-selectable genes in retroviral vectors under control of an internal ribosome entry site.we describe a new retroviral vector system psxlc/pha that utilizes a putative internal ribosome entry site (ires) from encephalomyocarditis virus downstream from a multicloning site to co-express drug-selectable markers with a second non-selectable cdna in a eukaryotic expression vector. the positive drug-selectable marker, mdr1, and the positive-negative marker, herpes simplex virus thymidine kinase (hsv-tk), were successfully introduced and expressed in the psxlc/pha system. the psxlc-mdr and ...19947764914
binding of eukaryotic initiation factor-2 and trans-acting factors to the 5' untranslated region of encephalomyocarditis virus rna.the encephalomyocarditis virus 5' untranslated region (emc 5' utr) has a binding site for eukaryotic initiation factor eif-2. mutations in the 3' end or deletion of the 5' end of the internal ribosomal entry site had a negative effect on the binding of eif-2 to the emc 5' utr. the binding of eif-2 to the mutant 5' utrs was completely inhibited by the addition of competitor trna. cross-linking of the emc 5' utr with proteins from rabbit reticulocyte lysates showed binding of trans-acting factors ...19947893829
in vivo augmentation of ifn-gamma with a ril-12 human/mouse chimera: pleiotropic effects against infectious agents in mice and rats.a heterodimer containing the mouse 35 kda and human 40 kda subunit of il-12 was expressed in cos cells (cil-12). administration of 25-200 u of the cil-12-cos supernatant to mice twice daily for 2 days augmented spleen cell ifn-gamma production in response to il-2 and peritoneal macrophage activity (superoxide and nitrites) as compared to animals receiving mock transfected supernatants. cil-12 also increased levels of ifn-gamma in serum but most dramatically following an lps injection (50-fold ov ...19947914437
drug-selected coexpression of human glucocerebrosidase and p-glycoprotein using a bicistronic vector.bicistronic cassettes under control of a single promoter have recently been suggested as useful tools for coordinate expression of two different foreign proteins in mammalian cells. using the long 5' untranslated region of encephalomyocarditis virus as translational enhancer of the second gene, a bicistronic unit composed of cdna for human p-glycoprotein [the product of the multidrug resistance gene, mdr1 (also called pgy1)] as selectable marker and cdna for human glucocerebrosidase (gc; ec 3.2. ...19947909160
identification and characterization of the cell surface 70-kilodalton sialoglycoprotein(s) as a candidate receptor for encephalomyocarditis virus on human nucleated cells.the attachment of encephalomyocarditis (emc) virus to human nucleated cells susceptible to virus infection was examined with hela and k562 cell lines. both cell types showed specific virus binding competitively blocked by unlabeled virions. the number of binding sites for emc virus on hela and k562 cells were approximately 1.6 x 10(5) and 3.5 x 10(5) per cell, respectively, and dissociation binding constants were 1.1 and 2.7 nm, respectively. treatment of cells with cycloheximide after pretreatm ...19947933115
specific inhibition of aphthovirus infection by rnas transcribed from both the 5' and the 3' noncoding regions.rna molecules containing the 3' terminal region of foot-and-mouth disease virus (fmdv) rna in both antisense and sense orientations were able to inhibit viral fmdv translation and infective particle formation in bhk-21 cells following comicroinjection or cotransfection with infectious viral rna. antisense, but not sense, transcripts from the 5' noncoding region including the proximal element of the internal ribosome entry site and the two functional initiation augs were also inhibitory, both in ...19947933126
survey for selected diseases in nutria (myocastor coypus) from louisiana.thirty-two trapper-caught nutria (myocastor coypus) from east baton rouge, iberville, tangipahoa, and st. helena parishes in louisiana (usa) were sampled for several disease agents. antibodies against toxoplasma gondii, chlamydia psittaci, francisella tularensis, leptospira spp., and encephalomyocarditis virus were detected in 7%, 14%, 0%, 7%, and 0% of nutria, respectively. both animals seropositive for leptospirae were positive for l. interrogans serovar canicola. no salmonella spp. were isola ...19947933295
autoantibodies against vimentin in a murine model of myocarditis.the presence of autoantibodies in the sera of patients with myocarditis has suggested that autoimmunity is a sequela of myocarditis. in this study, we examined anti-vimentin antibodies in a murine model of myocarditis. four-week-old male dba/2 mice were inoculated intraperitoneally with 10 plaque-forming units of encephalomyocarditis (emc) virus. the surviving mice were killed on days 0 (n = 7), 2 (n = 6), 5 (n = 6), 7 (n = 6), 9 (n = 6), 14 (n = 5), 60 (n = 6) and 540 (n = 3) after virus inocul ...19947742476
construction and characterization of retroviral vectors expressing biologically active human interleukin-12.interleukin-12 (il-12) is a heterodimeric cytokine originally defined by its ability to induce the maturation of cytolytic lymphocytes and by its capacity to effectively synergize with il-2 in the induction of cytolytic activity. recent studies in mice have demonstrated the ability of il-12 to cause tumor regression and stimulate long-term antitumor immunity in treated animals. to examine the antitumor effect of direct gene transfer of il-12 into tumors, we have developed retroviral vectors that ...19947711142
vcam-1 is a receptor for encephalomyocarditis virus on murine vascular endothelial cells.murine vcam-1 has been identified as a receptor for the d variant of encephalomyocarditis (emc-d) virus on vascular endothelial cells from the heart. monoclonal antibodies to vcam-1 inhibited infection and lysis of endothelial cells with emc-d virus. cho cells transfected with the vcam-1 gene were susceptible to emc-d virus lysis, while control cho cells transfected with the elam-1 gene were resistant. similarly, 35s-labeled emc-d virus bound to cho-vcam cells, and binding was inhibited with ant ...19947514674
introduction of foreign sequences into the genome of influenza a virus.the ability to apply reverse genetics technologies to influenza virus now allows us to construct novel viruses containing heterologous sequences. we have engineered two neuraminidase (na) genes of influenza a/wsn/33 virus containing additional sequences which were inserted downstream of the open reading frame of the na. these na genes, na/emc and na/emc-ns1, possess a 546 and a 917 nucleotide (nt) insertion respectively. transfectant viruses were rescued following ribonucleoprotein (rnp) transfe ...19947525392
analysis of hepatitis a virus translation in a t7 polymerase-expressing cell line.hepatitis a virus (hav) exhibits several characteristics which distinguish it from other picornaviruses, including slow growth in cell culture even after adaptation, and lack of host-cell protein synthesis shut-down. like other picornaviruses, hav contains a long 5' nontranslated region (ntr) incorporating an internal ribosomal entry site (ires), which directs cap-independent translation. we compared hav ires-initiated translation with translation initiated by the structurally similar encephalom ...19948032260
the complete nucleotide sequence and construction of an infectious cdna clone of a highly virulent encephalomyocarditis virus.the nucleotide sequence of a highly variant of the encephalomyocarditis virus, pv21, was determined. discounting the poly(a) tail the viral genome is 7.861 kb in length, including a poly(c) region of 157 or 158 nucleotides. the sequence differs in 38 positions from another virulent emcv variant, emcv-r (1). however, the pv21 sequence shows only 85% identity with two nonlethal variants isolated in this laboratory (2). a cdna clone covering the complete virus sequence including a poly(c) region of ...19948053159
ires-controlled protein synthesis and genome replication of poliovirus.initiation of translation of the single-stranded genomic rnas of picornaviruses such as poliovirus (pv) and encephalomyocarditis virus (emcv) is cap-independent and controlled by a long segment within the 5' non-translated region (5'ntr), termed internal ribosomal entry site (ires). cellular rna-binding proteins have been identified that are involved in ires function in trans. one of these proteins (p57) has been found to be identical to the polypyrimidine tract binding protein (pptb), a nuclear ...19948032259
internal translation initiation on poliovirus rna: further characterization of la function in poliovirus translation in vitro.initiation of poliovirus rna translation by internal entry of ribosomes is believed to require the participation of trans-acting factors. the mechanism of action of these factors is poorly defined. the limiting amount of one of these factors, la protein, in rabbit reticulocyte lysates (rrl) has been postulated to partially explain the inefficient translation of poliovirus rna in this system. to further characterize la activity in translation and to identify other potential limiting factors, we a ...19948107217
translation of encephalomyocarditis virus rna: parameters influencing the selection of the internal initiation site.the initiation of encephalomyocarditis virus rna translation is by internal ribosome entry almost exclusively at the 11th aug codon from the 5'-end, which is the central of the three aug codons in the sequence..[sequence: see text].., and is located some 25 nt downstream from an oligopyrimidine tract conserved amongst related viruses. as the sequences between the oligopyrimidine tract and aug-10/11 are poorly conserved and thus possibly serve only as a spacer, the influence of this spacer length ...19948157006
pyrimidine tract binding protein strongly stimulates in vitro encephalomyocarditis virus rna translation at the level of preinitiation complex formation.cellular protein p57/58, now known to be identical to polypyrimidine tract binding protein (ptb), has earlier been shown to specifically bind to the internal ribosome entry sites (ires) of encephalomyocarditis virus (emcv) and some other picornaviral rnas. to elucidate its relevance to the internal initiation, the effect of cloned purified ptb on emcv ires directed translation was studied in cytoplasmic extracts of krebs-2 ascites carcinoma cells partially depleted of endogenous ptb. addition of ...19948082784
inactivation of lipid-enveloped and non-lipid-enveloped model viruses in normal human plasma by crosslinked starch-iodine.the purpose of this study was to evaluate an iodine-based method of activating potentially harmful viruses that might be found in normal human plasma.19948178330
therapeutic effect of anti-tumor necrosis factor-alpha antibody on the murine model of viral myocarditis induced by encephalomyocarditis virus.tumor necrosis factor-alpha (tnf-alpha) has been reported to have an antiviral effect in vitro; however, its in vivo effect remains to be clarified.19948313574
in vitro characterization of an internal ribosomal entry site (ires) present within the 5' nontranslated region of hepatitis a virus rna: comparison with the ires of encephalomyocarditis virus.the lengthy 5' nontranslated region (5'ntr) of hepatitis a virus (hav) forms a highly ordered secondary structure, which has been suggested to play an important role in controlling viral translation by allowing for translation initiation by internal ribosome entry. to test this hypothesis, synthetic bicistronic rnas, with all or part of the hav 5'ntr in the intercistronic space, were translated in rabbit reticulocyte lysates. in the presence of an upstream cistron designed to block ribosomal sca ...19948289336
detection by a solid phase independent enzyme immunoassay of monoclonal anti-idiotypic antibodies against monoclonal antibodies neutralizing semliki forest virus and encephalomyocarditis virus.neutralization inhibition enzyme immunoassay (ni-eia) was evaluated for its usefulness to detect monoclonal anti-idiotypic antibodies (ab2mabs) against idiotypic monoclonal antibodies (ab1mabs) neutralizing either semliki forest virus (sfv) or encephalomyocarditis virus (emcv). purified ab1mabs were coupled to keyhole limpet hemocyanin (klh) mixed with the adjuvant quil a and then injected intracutaneously into homologous balb/c mice. successful fusions were performed 5, 6 and 7 days after intra ...19938396153
experimentally produced nonantibody inhibitors of encephalomyocarditis virus in vitro activity. 19938385503
the encephalomyocarditis virus 3c protease is rapidly degraded by an atp-dependent proteolytic system in reticulocyte lysate.the encephalomyocarditis virus 3c protease has been observed to undergo rapid degradation, both in vivo in mouse cells and in vitro in reticulocyte lysate. experiments were carried out to characterize the turnover of the 3c protease in reticulocyte lysate. 3c protease prepared in reticulocyte lysate by in vitro translation and processing of a precursor polyprotein could be separated from the proteolytic activity responsible for its degradation. this implies the 3c protease is not directly involv ...19938382397
a serological survey of encephalomyocarditis virus infection in pigs in japan.a total of 1502 pig sera collected between 1990 and 1991 at 65 farms in 22 prefectures were subjected to neutralization test to encephalomyocarditis (emc) virus. of them, three hundred eighty seven pigs (25.8%) from the 55 farms (84.6%) had antibody against emc virus. the positive rates were rather high in ehime (53.1%), tottori (49.1%), shimane (44.4%) and nagasaki (38.7%). the positive rate and geometric mean titer of antibody tended to increase with the age. these serological results suggest ...19938384893
inhibition of proteolytic activity of poliovirus and rhinovirus 2a proteinases by elastase-specific inhibitors.a polyprotein cleavage assay has been developed to assay the proteolytic activities in vitro of the 2a proteinases encoded by poliovirus and human rhinovirus 14, which are representative members of the enterovirus and rhinovirus genera of picornaviruses, respectively. the elastase-specific substrate-based inhibitors elastatinal and methoxysuccinyl-ala-ala-pro-val-chloromethylketone (mpcmk) inhibited both 2a proteinases in vitro. the electrophoretic mobilities of both 2a proteinases were reduced ...19938392608
development of a radiolabeled nucleic acid probe for the detection of encephalomyocarditis virus of swine. 19938389600
experimental encephalomyocarditis virus infection in pigs.a field isolate of encephalomyocarditis (emc) virus was inoculated intravenously into 8 pigs. four animals died at post inoculation day (pid) 2, the remaining being sacrificed at pid 5, 7, 11 and 15. two control, in-contact pigs were sacrificed at pid 19. virus was isolated from leucocytes and nasal swabs until pid 4, from rectal swabs until pid 2 and, in the pigs found dead at pid 2, from several organs. emc virus was further isolated from brain and spleen of the pig sacrificed at pid 7. one of ...19938237207
the influence of viral coding sequences on the efficiency of internal initiation of translation of cardiovirus rnas.since internal initiation of translation of cardiovirus rnas requires the approximately 450-nt segment of the viral genome immediately upstream of the authentic initiation codon for viral polyprotein synthesis, the question arises as to whether the immediately adjacent sequences, the start of the polyprotein coding region, also influence the efficiency of internal initiation. therefore, a variety of constructs derived from encephalomyocarditis virus and theiler's murine encephalomyelitis virus r ...19938249303
internal ribosome entry site of encephalomyocarditis virus rna is unable to direct translation in saccharomyces cerevisiae.to evaluate the potential of the encephalomyocarditis virus (emcv) internal ribosome entry site (ires) to promote efficient expression of foreign genes in the yeast, s. cerevisiae, we have constructed e. coli-yeast shuttle vectors in which the emcv 5' non-coding region was fused to the reporter gene, human prothymosin alpha. efficiency of translation of corresponding rna transcripts in mammalian cell-free systems was highly dependent on the sequence context and/or position of the initiation codo ...19938253211
quercetin potentiates tnf-induced antiviral activity.tumor necrosis factor (tnf) produces a dose-dependent inhibition of vesicular stomatitis virus (vsv), encephalomyocarditis virus (emcv), and herpes simplex virus type 1 (hsv-1) replication in wish cells. the antiviral activity of tnf against vsv and emcv is greatly enhanced by combination with quercetin. induction of 2',5'-oligo-adenylate (2-5a) synthetase by tnf is also enhanced by quercetin. addition of polyclonal antibodies to human interferon (ifn)-beta completely blocked both enhancement of ...19938279819
hplc is an effective and fast method for analysis of viral proteins: a study of encephalomyocarditis virus mutants differing in pathogenicity.we investigated the use of hplc in analysis of picornavirus variants by comparing structural polypeptides of three stable mutants of encephalomyocarditis virus (emcv). the variants are known to differ in their pathogenicity for mice: plaque variant 2 (pv2) is diabetogenic, pv7 is non-diabetogenic and pv21 induces a generalized lethal infection. we first used hplc to separate the structural proteins at high purity levels. detailed analysis of these structural proteins by hplc-peptide mapping reve ...19938277283
detection of a shared idiotope on two encephalomyocarditis virus neutralizing monoclonal antibodies by neutralization inhibition enzyme immunoassay.idiotypic cross-reactivity between encephalomyocarditis virus (emcv) neutralizing monoclonal antibodies um 21.1 (igg2b) and um 21.3 (igg2a) was detected by neutralization inhibition enzyme immunoassay using polyclonal and monoclonal anti-idiotypic antibodies. one strongly cross-reactive anti-idiotypic monoclonal antibody, designated 21.1a5 (igg2b), might recognize a recurrent idiotope on emcv neutralizing antibodies but it did not induce emcv neutralizing anti-anti-idiotypic antibodies in homolo ...19938263123
does the gender difference in interferon production seen in picornavirus-infected spleen cell cultures from icr swiss mice have any in vivo significance?splenocyte cultures from female icr swiss mice produced greater interferon (ifn) levels, particularly ifn-gamma, than did cultures from males by 12 h post-infection (pi) with the d variant of encephalomyocarditis virus (emcv-d). this early ifn-gamma is produced by natural killer (nk)-like cells and is dependent on plastic adherent cells and ifn-alpha/beta. in this study, we evaluated the significance of this observation on the innate resistance of icr swiss females to emcv-d-mediated disease. tr ...19937512115
transgenic mice carrying interferon genes. 19937504924
a dominant negative mutant of 2-5a-dependent rnase suppresses antiproliferative and antiviral effects of interferon.2-5a-dependent rnase is the terminal factor in the interferon-regulated 2-5a system thought to function in both the molecular mechanism of interferon action and in the general control of rna stability. however, direct evidence for specific functions of 2-5a-dependent rnase has been generally lacking. therefore, we developed a strategy to block the 2-5a system using a truncated form of 2-5a-dependent rnase which retains 2-5a binding activity while lacking rnase activity. when the truncated rnase ...19937688298
analysis of the human t-cell response to picornaviruses: identification of t-cell epitopes close to b-cell epitopes in poliovirus.little is known about the nature and specificity of t-cell-mediated responses to picornaviruses in humans. in this study, the nature of the t-cell response to seven picornaviruses, including polioviruses, coxsackieviruses b3 and b4, human rhinovirus 14, and encephalomyocarditis virus, was determined. twenty-nine individuals responded to poliovirus type 3, coxsackievirus b3, and encephalomyocarditis virus by proliferation of t cells, and from such cultures, 130 virus-specific t-cell lines were es ...19937679749
antiviral action of trehalose dimycolate against emc virus: role of macrophages and interferon alpha/beta.preventive treatment of mice with trehalose 6,6' dimycolate (tdm), an immunomodulator of bacterial origin, enhances their resistance to encephalomyocarditis (emc) virus infection. the protective effect of tdm is totally abolished by the injection of silica particles in mice, demonstrating the role of macrophages in the antiviral action of tdm. in vitro, peritoneal macrophages from mice treated with tdm (tdm-pm) exhibit an intrinsic antiviral activity against emc virus, while resident peritoneal ...19937506511
gene targeting in human somatic cells. complete inactivation of an interferon-inducible gene.the role, if any, of the human interferon-inducible 6-16 gene in the establishment of a cellular antiviral state is unknown. to address this problem, and as part of a wider investigation of homologous recombination (hr) and its applications in somatic cells, we have been using hr to disrupt the 6-16 gene in human cell lines [itzhaki, j. e. & porter, a. c. g. (1991) nucleic acids res. 19, 3835-3842.] we describe here the design and use of insertion and replacement-type targeting constructs based ...19937505743
molecular identification of cardioviruses by enzymatic amplification.cardiovirus specific sequences located in the 5' ntr are used to amplify viral rna by pcr. general primers were selected for the amplification of cardioviruses, including encephalomyocarditis virus (emcv), mengovirus and theiler's murine encephalomyelitis virus (tmev. additionally, echo virus type 22, an atypical enterovirus, could also be detected with the general cardiovirus primers. an internal encephalomyocarditis virus specific probe and a general cardiovirus probe are used to discriminate ...19937511789
low-dose combination therapy with metoprolol and captopril for congestive heart failure in mice.we assessed the therapeutic efficacy of a low-dose combination of metoprolol and captopril given orally to c3h/hej mice that developed dilated and hypertrophied hearts after being inoculated with the encephalomyocarditis virus. mice were randomly assigned to one of six 8-week oral regimens: 1 mg/kg/day of metoprolol (group 1); 10 mg/kg/day of metoprolol (group 2); 1.2 mg/kg/day of captopril (group 3); 12 mg/kg/day of captopril (group 4); 1 mg/kg/day of metoprolol plus 1.2 mg/kg/day of captopril ...19938110623
polymyositis and dermatomyositis: no persistence of enterovirus or encephalomyocarditis virus rna in muscle.a persistent infection of enteroviruses and cardioviruses has been implicated in polymyositis and dermatomyositis, but conventional hybridisation studies of the presence of enterovirus rna and encephalomyocarditis (emc) virus rna in affected muscle have yielded conflicting results. to investigate further the possibility of viral persistence, the presence of viral rna in muscle from patients with adult onset polymyositis and dermatomyositis was investigated using a polymerase chain reaction (pcr) ...19938215618
biphasic disease of central nervous system induced in dba/2 mice by the d variant of encephalomyocarditis virus (emc-d).dba/2 mice infected with the d variant of encephalomyocarditis virus (emc-d) (10(1) pfu/head) developed biphasic hind limb paralysis. at 12 days post inoculation (12 dpi), 60% of the infected mice developed hind limb paralysis and two-thirds of them showed recovery by 33 dpi. thereafter, about 30% of the mice which once showed paralysis developed hind limb paralysis again by 56 dpi. histopathologically, the spinal cord lesion of paralysed mice was characterized by demyelination associated with i ...19938217784
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