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antiviral pyrimidine derivatives: binding with biopolymers and photosensitization.two antiviral pyrimidine derivatives, known to partially inhibit rna dependent rna polymerase of mengo virus in a cell-free system, were found to bind with biopolymers. the antiviral compounds, at concentration of 100 and 50 mum and lower, showed complete inhibition of the virus-induced cytopathic effect and plaque reduction. both compounds showed fluorescence emission with a maximum at about 500 nm under the influence of uv light of the wavelength of 366 nm. the fluorescence intensity increased ...197825007
effect of 3-bis-(2-hydroxyethyl)-amino-acetophenone-4.5-diphenyl-oxazolyl-(2)-hydrazone (imet 98/69) on lethal mengo virus encephalitis.3-bis-(2-hydroxyethyl)-amino-acetophenone-4.5-diphenyl-oxazolyl-(2)-hydrazone (imet 98/69) was found to afford maximum "rates of protection" in intraperitoneally (i.p.) or intranasally (i.n.) induced mengo virus encephalitis in mice when administered once daily at doses of 1 mmole/kg (456.5 mg/kg) subcutaneously (s.c.) or 4 mmoles/kg (1 826 mg/kg) perorally (p.o.). three days of treatment were sufficient if started on the day before or at the time of virus inoculation. initiation of treatment 6 ...197825008
replication of mengovirus in ehrlich ascites carcinoma cell suspension cultures. 2. obtaining high titer partially purified virus suspensions. 197827896
antiviral activity of dipyridamole derivatives.among 46 novel pyrimido 5.4-d pyrimidine derivatives, 26 compounds were found to exhibit antiviral activity as revealed in a test programme against mengo, coxsackie b1, fowl plague, vaccinia and pseudorabies viruses, as concerns inhibition of plaque formation and of infectious virus yield. attempts to disclose structure-activity relationships by discriminant analysis pointed to a possible importance of hydrophobic substitution for the antiviral effectiveness against mengo virus of the derivative ...197829467
antiviral activity of certain isatinisothiosemicarbazones against mengo and vaccinia virus infections in mice.among eleven isatinisothiosemicarbazones (iits) examined only 1-ethylisatin-s-n-butylisothiosemicarbazone (zimet 189/69) proved to be significantly effective against lethal mengo and neurovaccinia virus-induced encephalitis in mice when administered subcuaneously (s.c.) in doses of 1 mmole/kg body weight per day. with peroral (p.o.) administration all the drugs failed to prevent mortality in mengo virus-infected mice. against this virus zimet 189/69 was effective over a concentration range from ...197935958
comparison of antiviral properties in mice of bis-pyrrolidinoacetamido-fluorenone (mlu-b75), bis-dipropylaminoacetamido-fluorenone (mlu-b76), and tilorone hydrochloride.like tilorone . hcl, its analogues, bis-pyrrolidinoacetamido-fluorenone (mlu-b75), and bis-dipropylaminoacetamido-fluorenone (mlu-b76), significantly protected mice against intraperitoneal challenge with a lethal dose of mengo virus when administered prophylactically in a single oral dose of 250 mg per kg body weight. at lower doses the antiviral activity of mlu-b75 and mlu-b76 decreased more rapidly than that of tilorone. hcl. at the dose of 250 mg per kg the degree of antiviral protection and ...197939439
physiological characterization of temperature-sensitive mutants of mengovirus.twenty-four temperature-sensitive mutants of mengovirus were characterized physiologically with respect to phenotype. the mutants were separated into four classes on the basis of viral rna synthesis. l-67-s cells infected with five of the mutants synthesized little viral rna at 39.5 c. these mutants are designated rna-. one mutant is designated rna* since its rna synthesis is altered at both 39.5 and 31.5 c. the other mutants were divided into two groups, rna plus or minus (25 to 49% of wild-ty ...1975163356
host-dependent restriction of mengovirus replication. iv. effect of some quaternary ammonium ions on the restricted replication of mengovirus in madin-darby bovine kidney cells.the quaternary ammonium ions, choline, hexamethonium, and tetraethylammonium, partially reliev the restricted replication of mengovirus in madin-darby bovine kidney cells.1975163914
host-dependent restriction of mengovirus replication. ii. effect of host restriction on late viral rna synthesis and viral maturation.restricted mengovirus replication in mandin-darby bovine kidney (mdbk) cells is characterized by a 400-fold reduction in infectious virus yield and a 40-fold increase in the production of noninfectious virus. using conditions which insure that all mdbk cells are infected, virus-specific rna and protein synthesis were measured in the restrictive host and in a permissive host for mengovirus, hela cells. labeling kinetics and sucrose gradient analysis of mengovirus-specific rna from mdbk cells show ...1975163923
stable polypeptides associated with the 250s mengovirus-induced rna polymerase structure.one host polypeptide (40,000 daltons) synthesized prior to infection is associated with the 250s rna polymerase structure partially purified by a combination of velocity sedimentation and isopycnic separation. a series of pulse-chase experiments have shown that a 56,000 dalton polypeptide made during the eclipse phase of infection is inserted into the 250s viral rna polymerase structure. this 56,000 dalton polypeptide is bound in a stable manner since labeled 56,000 dalton polypeptide is not rem ...1975164160
evidence for control of translation of the viral genome during replication of mengo virus and poliovirus. 1975169625
[antiviral thiosemicarbazone and related compounds. iii. quantitative relationships between structure and antiviral activity of isantin-beta-isothio-semicarbazone against mengo virus].the virostatic activity of isatin-beta-isothiosemicarbazones can be described quantitatively by hydrophobic, electronic, and steric substituent constants using multivariate regression analysis. a preceding free-wilson analysis allows data smoothening, and thus improved adaptation. predictions made on the basis of the quantitative structure-action relationships obtained could be confirmed experimentally by synthesizing and testing the corresponding compounds.1975171890
[in vitro evaluation of antiviral inhibitors by means of a turbidity method (author's transl)].the paper presents a photometric method for the determination of virus-induced alterations (cytopathogenic effects) of cells based on nephelometric analysis. these were taken at varying time intervals after infection and with different multiplicity of infection. it was demonstrated that suppression of virus-induced cpe by the known inhibitors could also be followed by turbidity measurements. the in vitro experiments were carried out in the 2 following virus-cell-systems: pseudorabies virus in ch ...1975171906
antiviral 1,3,4-thiadiazoles. ii. effects on cellular and viral rna synthesis in mengo-virus-infected fl cells.three antiviral 1,3,4-thiadiazoles caused, when incubated together with 3h-uridine, a reduction of the incorporation rate into acid-insoluble material of fl cells. using the method of prelabelling cellular rna synthesis was not remarkably influenced. however, the substances tested act as specific inhibitors of the virus-induced rna synthesis.1976176014
cellular protein synthesis shutoff by mengovirus: translation of nonviral and viral mrna's in extracts from uninfected and infected ehrlich ascites tumor cells.the mechanism whereby picornaviruses inhibit host protein synthesis while their own synthetic processes proceed unabated has remained elusive. one of our approaches to this problem was to study the ability of cell-free extracts derived from uninfected and mengovirus-infected ehrlich ascites tumor cells to translate viral and nonviral mrna's under various conditions of incubation. our results indicate that viral messengers (from mengovirus and encephalomyocarditis virus) and cellular messengers [ ...1976176460
interferon-sensitive mutants of mengovirus. i. isolation and biological characterization. 1976176792
isolation and partial characterization of temperature-sensitive mutants of mengo virus. 1976176801
considerations on structure-activity relationships with mengovirus of substituted 5-amino-4-cyanopyrazoles.in a screening program using the agar diffusion-plaque inhibition test, 22 out of 27 substituted aminopyrazoles tested showed marked antiviral activity against mengovirus in fl cell cultures. the efficacy of the different derivatives was compared by determining their effect on the yield of infectious virus after a one-step growth cycle. the antiviral activity against mengovirus correlated with the chain length of the substituents and increased or decreased according to the position of the side c ...1976176931
mode of action in vitro against mengovirus of substituted 5-amino-4-cyanopyrazoles.substituted amino pyrazoles were found to exhibit plaque reduction and inhibition of the cytopathic effect of mengovirus on fl cells. their antiviral activity was not caused by a virucidal effect or by inhibition of viral adsoprtion or penetration but by suppression of the virus multiplication. during a one-step growth cycle maximum suppression of virus yield occurred after compound addition from 0 to 2 h after infection. progressively less viral inhibition appeared when compound was applied dur ...1976176932
processing of mengovirus precursor polypeptides in the presence of zinc ions and sulfhydryl compounds.the effect of zinc ions on the post-translational cleavage of mengovirus polypeptides has been examined. the cleavage of the "a" precursor, which gives rise to the capsid proteins, was the most sensitive at concentrations of zinc chloride from 0.1 to 1.0 mm. beta-mercaptoethanol and dithiothreitol antagonized the zinc-promoted inhibtion of clevage. our results indicate that zinc ions interfere with the proper folding of the nascent polypeptide precursor rather than inhibit the proteases responsi ...1976178929
further studies on the relative antiviral efficacies of interferons induced by poly i:c and mengo virus.mouse serum interferons induced by polyi:c, vesicular stomatitis virus (vsv), reovirus, and mengo virus were assayed in monolayers of mouse l-929 cells by the plaque-reduction method using both vsv and mengo as challenge viruses. titers obtained with mengo virus as challenge were all lower than with vsv. with the interferons induced by vsv, reovirus, and ployi:c, the reductions were of the order of two- to three-fold. with mengo virus-induced interferon the reduction was much greater (about 17-f ...1976179687
human fibroblast and leukocyte interferons show different dose-response curves in assay of cell protection.preparations of human fibroblast and leukocyte interferons of similar potency show markedly different dose-response curves in an assay which measures the degree of protection of tissue cultures against virus c.p.e. the effect is observed with both vesicular stomatitis virus (vsv) and mengovirus, and is not altered by purification of the interferons.1976180244
chromosomal dna replication: retarded fork progression and altered initiation in cells infected with mengovirus or newcastle disease virus. 1976180665
polyadenylic acid in the genomic rna of mengovirus.the polyadenylic acid contained in 35s mengovirus rna produced in infected bhk-21 cells contained approximately 94% amp and was estimated to contain an average of 50 to 55 nucleotides. the polyadenylic acid is placed at the 3'-end of the genomic rna based on the presence of significant levels of [3h]adenosine in complete alkali or rnase t2 digests of polyadenylic acid from [3h]adenosine-labeled 35s viral rna.1976183022
testing of antiviral compounds against mengo virus infection of mice. a 2-step procedure of in vivo screening.a 2-step procedure of screening of antiviral compounds in vivo is presented on the basis of standardized methods of both experimental examination and statistical analysis. the procedure uses the "rate of protection" r as the sole criterion of activity. in the first step, requiring a total of 40 mice, compounds with significant r are detected. drugs producing r less than 15% are discarded. compounds eliciting r larger than or equal to 15%, without significance, are examined in a second step, usin ...1976184604
a comparison of the prophylactic and therapeutic effects of poly i:c and endotoxin in mice infected with mengo virus.we have compared the protective effect in akr mice of poly i:c and bacterial endotoxins against lethal doses of mengo virus. administered intravenously or intraperitoneally, both interferon inducers protected mice to about the same extent from virus challenges of 2-3 ld50's. endotoxin, however, was unable to protect the mice effectively against higher challenge doses of virus. evidence is presented that the level of protection afforded by both inducers is related to the level of circulating inte ...1976184902
dipyridamole, an inhibitor of mengovirus replication in fl and l cells.dipyridamole showed an antiviral activity aganinst mengovirus in fl cells using the agar diffusion plaque inhibition test, plaque reduction test, tube titration test, and virus yield test after one replication cycle. with the last two tests mentioned above the inhibitory action was also confirmed in l cells. in consequence of the known transport inhibition of uridine into the cell in presence of dipyridamole only a very small incorporation of 3h-uridine into acid-insoluble material could be demo ...1977189976
protein synthesis in postnuclear supernatants from mengovirus-infected ehrlich ascites tumor cells.the effect of mengovirus infection on the protein synthetic capacity of ehrlich ascites tumor cells cultured in vitro was studied in vivo and in vitro employing postnuclear supernatants prepared at various times post-infection in the absence and in the presence of 1% triton x-100. the amino acid incorporating activities of extracts obtained in the presence of the detergent were reduced by about 30% compared with the capacities of the corresponding postnuclear supernatants prepared in the absence ...1976190103
the size and location of the poly(a) tract in emc virus rna.encephalomyocarditis (emc) virus rna, selected by its affinity for oligo(dt)-cellulose, contains poly(a) of size : (i) about 14 nucleotide residues long, based on the percentage of radioactivity in the rna resistant to digestion by a mixture of pancreatic and t1 rnases; (ii) about 15 residues long, as measured by the ratio of the amount of terminal adenosine to internal adenylic acid in isolated poly(a); and (iii) in the range 12 to 45 residues, the majority of tracts being about 16 to 18 residu ...1977190347
factors affecting composition and thermostability of mengovirus virions.the composition of mengovirus virions produced by infected cells varies with the incubation temperature. virons produced at 37.0 or 39.5 degrees contain four major polypeptides (alpha, beta, gamma, and delta) and one minor polypeptide (beta'). virons produced at 31.5 degrees c contain two additional polypeptides (d1 and e). the virions of two temperature-sensitive (ts) and thermolabile mutants of mengovirus (ts25 and ts88) contain an increased amount of polypeptide beta', with a corresponding de ...1977191648
antiviral activity of certain hetarylhydrazones in mengo virus infected mice.out of a series of eleven related hetarylhydrazones four derivatives (zimet 124/73, zimet 38/74, zimet 44/69, and imet 98/69), after subcutaneous administration (0.5 mmole/kg per injection), were found to possess significant antiviral activity against rapidly progressing and highly lethal mengo virus encephalitis in mice. after peroral administration (2 mmole/kg per injection) only with imet 98/69 significant protection was achieved. drug treatments were given twice daily for 5 days. the effecti ...1977193309
shutoff of histone synthesis by mengovirus infection of ehrlich ascites tumor cells.the histone synthesizing capacity of mengovirus-infected ehrlich ascites tumor cells and of their corresponding postnuclear supernatants was investigated as a funcion of time post-infection. in addition, histone synthesis was compared with the synthesis of other basic host proteins under identical conditions. in the scope of mengovirus infection of ehrlich ascites tumor cells the less complex fraction comprising basic protein, separated from the acidic proteins by carboxymethyl cellulose chromat ...1977193773
studies of l cells persistently infected with vsv: factors involved in the regulation of persistent infection.infection of interferon-treated l cells with vsv led frequently to the establishment of l cells persistently infected with vsv (lvsv cells). these cells were characterized by the following properties; (i) no supplement of antiviral factors such as anti-vsv antiserum, interferon, was required for their maintenance; (2) virus antigens were detected in about 5 to 30% of the cells by immunofluorescence staining; (3) the cells were not only resistant to superinfection by homologous virus, but also re ...1977195007
alteration of the intracellular energetic and ionic conditions by mengovirus infection of ehrlich ascites tumor cells and its influence on protein synthesis in the midphase of infection.mengovirus infection of ehrlich ascites tumor cells caused a change of the intracellular atp concentration. it increased by 35% within the first 3 h postinfection and then declined to zero within the next 5 h. the decrease in the atp concentration was due, at least in part, to leakage of atp into the medium, where it could be demonstrated by the luciferin-luciferase assay. gross leakage of atp was observed at 4.5 h postinfection, concomitant with the production of the first intracellular, infect ...1977195079
purineless death: ribosomal rna turnover in a purine-starved ade- mutant of chinese hamster cells.when v79 pur 1, a purine-requiring auxotroph of a chinese hamster cell line, is deprived of adenine, nucleic acid and protein synthesis decline rapidly. however, on continuous starvation rna and dna synthesis recommences to reach approximately 30% of the normal level between 12 to 24 h starvation. this is accompanied by a rise in the intracellular nucleotide pool. utilizing mengovirus, which gives a productive infection in v79 pur 1 cells even under conditions of starvation, we can show that rrn ...1977195948
the genomic rna of mengovirus. i. location of the poly(c) tract. 1977196394
dna synthesis in mengovirus-infected cells: mechanism of inhibition. 1977200711
fate of histone messenger rna in mengovirus-infected ehrlich ascites tumor cells.histone mrna was isolated from mengovirus-infected ehrlich ascites tumor cells at various times postinfection and quantitated in a reticulocyte cell-free protein-synthesizing system. the amount of translatable histone mrna decreases during the first hour postinfection by 30%, rises during the following 1-1.5 h by 10-15%, drops progressively in the further course of infection, and reaches 20% of the control at the end of the infectious cycle (8-9 h postinfection). on the basis of the relative his ...1977202458
parameters of rna-dependent rna polymerase activity in a mengovirus-infected ehrlich ascites carcinoma cell-free system.virus-specific rna polymerase activity of mengovirus-infected ehrlich ascites carcinoma (eac) cells was maximal 7 hours after infection in a one-step growth cycle. in a cell-free system with the mitochondrial-microsomal fraction (mmf) derived from mengovirus-infected eac cells in a nucleoside-triphosphate medium, polymerase activity increased up to 60 min (when mmf was obtained by a homogenizer) or 120 min (when mmf was prepared by sodium deoxycholate disruption). subsequently rna polymerase act ...1977203090
identification and partial characterization of a new (50 s) subviral particle in mengo virus-infected l cells. 1978206009
assessment of cell-mediated hypersensitivity against coxsackievirus b3 viral-induced myocarditis utilizing hypertonic salt extracts of cardiac tissue.hypertonic kcl extracts prepared from heart tissues of adolescent cd-1 mice inoculated with coxsackievirus b3 (cvb3) were tested for antigenicity in evaluating cell-mediated sensitivity to cvb3 virus utilizing the agarose droplet cell-migration-inhibition assay. immune mouse peritoneal exudate cells (impec) from mice immunized against cvb3 virus and freund's complete adjuvant were specifically inhibited in the cell-migration-inhibition assay with graded doses of kcl-extracted antigen and purifie ...1978207775
the genomic rna of mengovirus. ii: comparative analysis of the standard and denser virions. 1978208232
saltatory thermal denaturation of double-stranded viral rnas.the double-stranded rnas from bacteriophage phi6 and the replicative form of mengovirus denature upon heating in a series of abrupt steps which resemble the subtransitions (thermalites) observed within the high resolution profiles of small, naturally occurring dna molecules. such rna thermalites are approximately an order of magnitude narrower than typical thermal subtransitions of nominally single-stranded rna. we conclude that the same features of nucleotide sequence that give rise to cooperat ...1978208611
[ribonucleic acid of mengo virus. part i. the isolation of mengovirus ribonucleic acid by gel chromatography]. 1978211709
[ribonucleic acid of mengo virus. part ii. characterization of native mengo virus ribonucleic acid]. 1978211710
in vitro translation of mengovirus rna deprived of the terminally-linked (capping?) protein. 1978215460
dephosphorylation of histone h1 after mengovirus infection of ehrlich ascites tumor cells.the effect of mengovirus infection on the extent of phosphorylation of histone h1 was studied in ehrlich ascites tumor cells. after prelabeling of the nuclear protein with [32p] orthophosphate, the excorporation of radioactivity was followed as a function of time postinfection. employing high-resolution polyacrylamide gradient slab gel electrophoresis and autoradiography, it was found that, compared to a relatively slow turnover of phosphate groups in histone h1 in mock-infected cells, in mengov ...1978216903
lipid-saccharide intermediates and glycoprotein biosynthesis in a temperature-sensitive chinese hamster cell mutant.the characterization of a temperature-sensitive chinese hamster cell mutant has been continued with the aim of localizing the apparent defect in glycoprotein synthesis (tenner et al., '77). although the mutation is lethal, a demonstration of the ability of the mutant cells to support proliferation of mengo virus at the nonpermissive temperature indicates that the general metabolic processes of the cells remain intact at a time when glycoprotein synthesis is severely depressed. a quantitative stu ...1979217883
[ribonucleic acid from mengo virus. iii. the different forms of ribonucleic acid]. 1979218340
location of enhanced ribonuclease activity and of a phosphoprotein kinase in interferon-treated mengovirus-infected cells. 1979218359
selective inhibition of protein synthesis in virus-infected mammalian cells.a number of translation inhibitors were tested for their effects on both control and encephalomyocarditis virus-infected mouse 3t6 cells. the virus-infected cells were specifically inhibited by gougerotin, edeine, and blasticidin s, whereas these drugs failed to penetrate into uninfected cells. inhibition of infected cells by gougerotin became apparent when the synthesis of viral proteins commenced, suggesting that the latter process is accompanied by a permeability change in the cells that allo ...1979219211
specific protein phosphorylation in interferon-treated uninfected and virus-infected mouse l929 cells: enhancement by double-stranded rna.the enhanced phosphorylation of specific protein(s) observed in extracts from interferon-treated cells (in the presence of atp and double-stranded [ds] rna) was also seen in intact mouse l929 cells upon treatment with dsrna, polyriboinosinic.polyribocytidylic acid [poly(ri.rc)] or reovirus dsrna, using 32pi as radiolabel. labeling of a 65,000-dalton protein(s) with 32p was greatly increased in interferon-treated cells in the presence of added dsrna, suggesting that the expression in vivo of the ...1979219224
infectivity of mengovirus replicative form. iv. intracellular conversion into replicative intermediate. 1979223306
protection of mice against infection with wild-type mengo virus and an interferon sensitive mutant (is-1) by polynucleotides and interferons.single-stranded polynucleotide preparations [trna, poly(ri) plus poly(ho5c)-copolymer] which protect mice against picornavirus infections without inducing interferon, protected mice equally against infection with an interferon-sensitive mutant (is-1) of mengo virus and with wild-type virus (is+). poly(ri) . poly(rc), and mouse macrophage interferon [i.e. serum from mice treated with poly(ri) . poly(rc)] protected mice equally against infections with the two viruses, but fibroblast interferon pro ...1979227997
mengovirus-induced inhibition of cell protein synthesis and subsequent recovery of cellular activity in interferon-pretreated cells. 1979228479
dimethyl-10,12-benz(a)acridine; evidence for differential effects on the synthesis of rna of mammalian or avian fibroblasts and some rna viruses.we have studied the differential effect of dimethyl-10,12-benz(a)acridine (dbmacr) on the synthesis of rna of chicken or mouse fibroblasts in culture and that of some rna-containing viruses such as rous sarcoma virus and mengovirus. dmbacr at low concentrations blocks the cell multiplication of both normal and rous sarcoma virus-transformed chicken fibroblasts in culture; it affects transformed cells more than normal ones. the cell growth inhibiting effect of dmbacr is reversible after short per ...1979219894
enhancement of the antiviral activity of pyrimidine derivatives against mengovirus by visible light.eleven pyrimido-pyrimidine derivatives, seven with significant antiviral activity against mengovirus, five against coxsackie b1 virus and four antiviral negative compounds were tested for their photosensitizing ability. all seven compounds with antiviral activity in vitro showed an enhanced antiviral action against mengovirus under irradiation with visible light, a fact that may be caused by photodynamic processes. it was tried to correlate the oxidation potentials of sensitizers with their phot ...1979232339
specific binding of messenger rna and methionyl-trnafmet by the same initiation factor for eukaryotic protein synthesis.affinity chromatography on columns containing globin mrna, r17 phage mrna, or double-stranded rna linked to cellose is used to demonstrate unequivocally that the eukaryotic initiation factor (eif-2) that forms a ternary complex with met-trnaf and gtp also binds tightly to these rna species. affinity chromatography of reticulocyte ribosomal wash yields over 100-fold purification of met-trnaf-binding factor. this factor is eluted as one of the most tightly bound proteins, and is active in protein ...1978272636
mengovirus-induced capping of virus receptors on the plasma membrane of ehrlich ascites tumour cells.mengovirus particles adsorbed to ehrlich ascites tumour cells are redistributed into patches and caps without the action of antibodies. thus capping may be an early signal in picornavirus infection.1979217969
properties of morphologically variant haploid frog cells formed by combined treatment with mengo virus and the polyene antibiotic mediocidin.comparisons have been made of cell surface glycoproteins, concanavalin a agglutinability, and cloning efficiencies in liquid media of icr 2a (haploid frog cells), icr 2a m (three cloned populations of haploid frog cells resistant to 5 microgram per ml of the polyene antibiotic mediocidin), and icr 2a m/mv cells (five cloned populations of morphologically variant haploid frog cells produced by exposure of the parental cells to the combined effects of mediocidin and an rna mammalian virus, mengo v ...1978216628
translation of animal virus rna in the cytoplasm of a plant cell.isolated acetabularia crenulata nuclei were injected with mengo virus rna solution and then implanted into anucleate posterior acetabularia mediterranea cell fragments or fused with acetabularia ryukyuensis cytoplasts. the injected animal virus rna was actively translated in the plant cell cytoplasm. mengo virus proteins were detected and localized in acetabularia cytoplasts by use of an immunofluorescence method on the first to fifth day after injection.1978214792
differential inhibition of host cell rna synthesis in several picornavirus-infected cell lines.patterns of cellular rna synthesis during poliovirus (types 1,2 and 3) and mengovirus infections in hela, hep-2, vero and l-cells were investigated by means of high-resolution autoradiography, kinetics of 3h-uridine incorporation, and sucrose gradient centrifugation. only mengovirus-infected l-cells showed an early and exponential inhibition of hnrna and rrna synthesis. the other cell lines tested, whether infected with polio- or mengovirus, exhibited a slowly and linearly decreasing cellular rn ...1978210138
effect of treatment with certain flavonoids on mengo virus-induced encephalitis in mice.among the four flavonoids tested quercetin and morin proved to be significantly effective against lethal mengo virus-induced encephalitis in mice when the drugs were adminsitered orally (p.o.). with subcutaneous (s.c.) administration all four drugs failed to prevent mortality in the infected mice. quercetin produced maximum protective response in intraperitoneally (i.p.) or intranasally (i.nas.) infected mice when administered twice daily at doses of 20 mg/kg for a period of not less than four d ...1978209770
sequence and structural elements that contribute to efficient encephalomyocarditis virus rna translation.the nucleotide sequence of the 5' nontranslated region of encephalomyocarditis virus (emcv-rueckert) was determined, and a consensus rna structural model for this sequence (850 bases) and three other poly(c)-containing cardioviruses (mengovirus, emcv-b, and emcv-d) was created through reiterative use of a minimum-free-energy folding algorithm. the rna elements within this region which contribute to translation of emcv proteins were mapped in cell-free reactions programmed with cdna-derived rna t ...19921310768
enhanced phosphorylation of ribosomal protein s6 and other cytoplasmic proteins after mengovirus infection of ehrlich ascites tumor cells.after mengovirus infection of ehrlich ascites tumor cells, an increased incorporation of radioactive phosphate into ribosomal protein s6 was detected. as judged from the shape of the radioautography spot and the location of the modified protein on the two-dimensional polyacrylamide gel, it must be concluded that more than one phosphate group was incorporated into ribosomal protein s6. concomitantly, multiple cytoplasmic proteins, particularly those with high affinity for ribosomes, were phosphor ...1978208946
changes in the microheterogeneity of histone h1 after mengovirus infection of ehrlich ascites tumor cells.employing high-resolution polyacryl-amide gradient slab-gel electrophoresis in 6m urea and 6% acetic acid, a distinct change in the microheterogeneity of histone h1 was detected after mengovirus infection of ehrlich ascites tumor cells. whereas in uninfected cells the band multiplicity was found to be 6, it was reduced to 4 in the course of the infectious cycle (8 to 9 h). it could be deomonstrated that, while the electrophoretically slowly moving subspecies h1e and h1f disappeared from the band ...1978208945
molecular and structural basis of hemagglutination in mengovirus.the molecular and structural basis of mengovirus hemagglutination (ha) was investigated by the comparison of nucleotide sequences of the entire capsid coding regions of an ha+ variant, two ha- mutants, 205 and 280, and two ha+ revertants of 205. the mutants were selected after acridine mutagenesis of mengovirus-37a, a heat-stable and ha+ variant that is neurotropic in mice. ha+ revertants of mutant 205 were isolated from brain tissue of mice inoculated with mutant 205. the nucleotide sequences w ...19921326807
virus-specific effects of recombinant porcine interferon-gamma and the induction of mx proteins in pig cells.interferon-alpha (ifn-alpha) and -gamma differed in their action against influenza virus and vesicular stomatitis virus (vsv) on pig cells. recombinant ifn-alpha severely impaired the cytopathic effect of vsv on pk-15 cells, whereas recombinant porcine ifn-gamma did not. ifn-alpha impaired also the replication of vsv and of influenza virus in primary pig kidney cells in contrast to ifn-gamma, which failed to induce an efficient antiviral state against both viruses. otherwise, the ifn system seem ...19921337754
purification of mengovirus by freon extraction and chromatography on protein-coated controlled pore glass.mengovirus, extracted from infected l-cell cultures with freon 113 and concentrated from the aqueous phase with polyethyleneglycol, was chromatographed on protein-coated controlled pore glass (cpg). the covalent binding of protein to cpg is described. further purification and concentration of mengovirus was achieved by isopycnic density gradient centrifugation in solutions of either cscl or salts of iodinated benzoic acid derivatives. the described procedure is superior to conventional methods f ...1978206230
localization of host poly(a)+ mrna in the ribosome profile of mengovirus-infected ehrlich ascites tumor cells.the distribution of poly(a)+ mrna among polysomes, monosomes, and ribosome-free supernatant fractions after mengovirus infection of ehrlich ascites tumor (eat) cells was investigated employing sucrose gradient centrifugation of their corresponding postnuclear supernatants. poly(a)+ mrna was isolated from sucrose gradient fractions and quantitated in a cell-free protein synthesizing system from uninfected eat cells. it was also localized by annealing [3h]-poly(u) to the poly(a)-tracts of mrna pre ...1978205776
cell microfilaments disorganization is an early cytopathic effect in mengo virus replication.the effect of mengo virus replication on cell morphology and cytoskeletal organization has been studied in lw murine fibroblasts. cell modifications were followed by scanning electron microscopy. the cytoskeleton was stained by immunofluorescence using antitubulin antibodies for microtubules, antivimentin antibodies for intermediate filaments and rhodamine-conjugated phalloidin for microfilaments. cytopathic effects began in the early phase of virus infection amd were correlated with broad modif ...19911649961
selective translation of mengovirus rna over host mrna in homologous, fractionated, cell-free translational systems from ehrlich-ascites-tumor cells.the selective translation of viral rna in mengovirus-infected ehrlich ascites tumor cells was investigated using fractionated translational systems whose macromolecular components were derived entirely from uninfected or virus-infected cells. both systems translate host mrna from uninfected cells, host mrna from virus-infected cells, and mengovirus rna. in competition experiments, where viral rna and host mrna were translated together in systems from uninfected cells, the relative amounts of vir ...1978204478
translation of ascites and mengovirus rna in fractionated cell-free systems from uninfected and mengovirus-infected ehrlich-ascites-tumor cells.we have prepared homologous, fractionated, cell-free translational systems from uninfected and mengovirus-infected ehrlich ascites tumor cells in order to determine what alterations occur following virus infection in the translational machinery of the host cell. two major differences distinguish the system developed from infected cells. first, it has a 40% lower rate of protein synthesis, primarily a consequence of the rate of chain elongation, which is depressed to 60 amino acids/min from 90 am ...1978204477
characterization of mengo virus neutralization epitopes.a set of four monoclonal antibodies which neutralized the infectivity of mengo virus was used to select 20 non-neutralizable (escape) mutants. altered amino acids were identified by sequence analyses of the capsid-coding regions of the mutant virus genomes. mutations were found predominantly in proteins vp2 and vp3, while mutations in vp1 were detected only as second mutations. the mengo virus vp2 mutations at amino acid residues 2144, 2145, 2147, and 2148 align with site nlm ii in human rhinovi ...19911704653
cellular rna synthesis in normal and mengovirus-infected l-929 cells.cellular rna synthesis was studied in mouse l-929 cells and in these cells infected with mengovirus. rna polymerases i, ii, and iii were partially purified and their chromatographic properties were analyzed by deae-sephadex a-25 chromatography. rna polymerase ii was purified from mouse liver and its subunit structure was compared to that of normal and virus-infected l-929 cells by two-dimensional gel electrophoresis. by these criteria, the enzymes from all three sources were identical. the rna s ...1978201639
coding capacity of poly(a)+mrna isolated from mengovirus-infected ehrlich ascites tumor cells.total poly (a)+mrna was isolated from mengovirus-infected ehrlich ascites tumor cells at various times postinfection and quantitated in a cell-free system derived from uninfected ascites cells. basic proteins were separated from acidic proteins by carboxymethyl cellulose chromatography. at the end of the infectious cycle, 8h postinfection, the cellular contents of most mrnas coding for basic ribosomal proteins are still between 70 and 90 percent of those measured at the beginning of infection or ...1977199833
an investigation of the stability of messenger rnas in cell-free, translational systems from uninfected and mengovirus-infected ehrlich ascites tumor cells.the stabilities and translation of ehrlich ascites tumor cell poly(a)-containing mrna and mengovirus rna in fractionated cell-free protein synthesizing systems from uninfected and mengovirus-infected ehrlich ascites tumor cells were studied. during incubation of the systems about 20% of the input rna is reduced in size and associated with ribosomes engaged in polypeptide synthesis; the remainder is rapidly degraded by rnases. at the end of active translation, both mrna and nascent proteins are b ...1977196186
functional aspects of the capsid structure of mengo virus.the three-dimensional structure of the mengo virus capsid has been determined at a resolution of 3.0 a. this achievement is discussed in an historical context, and the general features of picornavirus capsid design are presented. the dynamic functional aspects of the mengo virus capsid--namely its ability to interact with specific receptors on host cells, to dissociate and release the viral genomic rna into the cellular cytoplasm, to assemble with progeny rna molecules and form new virions, and ...19901965133
the role of viruses and environmental factors in the induction of diabetes.the development of iddm results from the destruction of pancreatic beta cells. genetic factors, various immune system alterations, and environmental factors have been studied as the possible causes of iddm. the concordance rate for developing iddm between monozygotic twins approaches 50%, suggesting that genetic factors are necessary, but nongenetic factors such as various immune system alterations and environmental factors also influence the clinical expression of genetic susceptibility. enviro ...19902073786
attenuation of mengo virus through genetic engineering of the 5' noncoding poly(c) tract.the murine cardioviruses, such as the mengo and encephalomyocarditis viruses, and the bovine aphthoviruses, such as foot-and-mouth disease virus, are distinguished among positive-strand rna viruses by the presence of long homopolymeric poly(c) tracts within their 5' noncoding sequences. although the specific lengths (60-350 bases) and sequence discontinuities (for example, uridine residues) that sometimes disrupt the homopolymer have served to characterize natural viral isolates, the biological ...19902153940
inhibition of cellular and viral protein synthesis by 3-methyleneoxindole.the effect of 3-methyleneoxindole (mo) on mengovirus and l-cell protein synthesis was investigated. mo was found to inhibit mengovirus multiplication and the incorporation of radioactive amino acids into both viral and cellular proteins. these results suggest that the antiviral effect of this compound is not specific but rather stems from its inhibition of the cellular translational machinery upon which mengovirus depends. we have also found that mo inhibits natural messenger ribonucleic acid (m ...1977193438
conformational variability of a picornavirus capsid: ph-dependent structural changes of mengo virus related to its host receptor attachment site and disassembly.the structure of mengo virus had been determined from crystals grown in the presence of 100 mm phosphate buffer at ph 7.4. it is shown that mengo virus is poorly infectious at the phosphate concentration similar to that in which it was crystallized. maximal infectivity is achieved at 10 mm phosphate or less in physiological saline. the phosphate effect is ameliorated when the ph is lowered to 4.6. although it has not been possible to study the crystal structure of the virus at low phosphate conc ...19902155508
structural refinement and analysis of mengo virus.the structure of mengo encephalomyelitis virus was refined at 3 a resolution with a final r-factor of 0.221 and a root-mean-square deviation from idealized bond lengths of 0.019 a for 10 a to 3 a data with f greater than or equal to 3 sigma(f). the hendrickson-konnert refinement was restrained by the phases derived from the molecular replacement averaging procedure and constrained by the icosahedral symmetry of the virus. the virus consists of 60 protomers each having three major subunits, vp1, ...19902156078
the inhibition of mouse l-cell 45 s ribosomal rna processing is a highly uv-resistant property of vesicular stomatitis virus.in mouse l cells infected with vesicular stomatitis virus (vsv), the synthesis of 45 s rrna and its conversion to 28 s and 18 s rrna are inhibited during the course of infection. evidence is presented that the lack of accumulation of stable rrna species results not only from the decreased transcription and processing of 45 s rrna, but also from an increased breakdown of pre-rrna or stable rrna during processing. in cells prelabeled with [3h]uridine and then infected, the 28 s and 18 s rrna speci ...19902162117
the use of a complementary dna probe to detect accumulation of mengo rna in infected cells pretreated with interferon.complementary dna (cdna) from mengo virus rna has been synthesized and used as a probe to measure the synthesis and accumulation of viral rna in mengo infected l cell cultures, treated or untreated with interferon. under experimental conditions used (200 units interferon/ml and 50 virus plaque-forming units/cell) results show that there is some synthesis of mengo virus rna in cells treated with interferon. one hour after infection, treated cells contain three times less viral rna than untreated ...1977192326
ph 2 instability of a mutant of mengovirus is related to its interferon sensitivity.the is-1 mutant of mengovirus is 100 times more sensitive to interferon (ifn) than wild type, as measured by a yield reduction assay in the g3 line of mouse l cells, and is also much more readily inactivated at ph 2. neither isolated nor encapsidated rna is degraded under these conditions, which suggests that the ph-sensitive region resides on the virus coat. one-third of the viruses selected for resistance to low ph also showed enhanced resistance to ifn. attempts to isolate ifn resistant strai ...19902172408
effects of pyrimidine derivatives on rna-dependent rna polymerase of mengovirus-infected fogh and lund (fl) cells.two newly synthesized pyrimidine derivatives were found to possess antiviral activity against mengovirus in fogh and lund (fl) cells and in a cell-free system. the inhibitory effect on rna-dependent rna polymerase of mengovirus-infected fl cells was assayed using 14c-utp as precursor. addition of 50 or 100 mum of the inhibitors in a cell-free system of crude enzyme and nucleoside triphosphate medium for 60 min incubation at 37 degrees c resulted in about 40 to 60% lower counting rates for drug-t ...1977188980
comparative studies on (2'-5')oligoadenylate-related enzyme systems and the antiviral effect of interferon in two mouse cell lines which differ in (2'-5')oligoadenylate sensitivity of their protein synthesizing system.effect of (2'-5')oligoadenylate (2-5a) on cellular and viral protein and rna syntheses was investigated with two mouse cell lines, l929 and lz (a subclone of l929). the oligonucleotide was introduced into the cells either by using calcium phosphate coprecipitation technique or by microinjection method. in l929 cells protein and viral rna syntheses were severely inhibited by 2-5a, whereas in lz cells, both were only slightly inhibited. the activities of 2-5a synthetase and double-stranded (ds)rna ...19852418128
antiviral activity of a chemically stabilized 2-5a analog upon microinjection into hela cells.2-5a[ppp(a2'p)n5'a] has been implicated as a mediator in the antiviral action of interferon. its direct evaluation as an indicator of virus replication is hampered by two limitations: its inability to penetrate intact cells, and its rapid intracellular degradation by (2'-5')phosphodiesterase. these problems could be overcome by using a microinjection technique whereby a phosphodiesterase-resistant analog of 2-a, in which the 2'-terminals adenosine residue is replaced by 2-(9-adenyl)-6-hydroxy-me ...19862420642
effect of actinomycin d on plaque formation by mengovirus.treatment of l cell monolayers with actinomycin d resulted in an increase in both the size and number of mengovirus plaques when compared to untreated cells. addition of the drug to the agar overlay was as effective as pretreatment provided the addition was immediately after virus adsorption. the increased plaque number observed was apparently not due to rescue of defective particles or inhibition of interferon production. the data indicate that more mengovirus particles can successfully complet ...1976185498
influence of certain immunodepressants on experimental flavivirus and enterovirus infections in mice.the effects of cyclophosphamide and 1,3-(piperidinomethyl)-5-phenyl-5-ethylbarbituric acid on certain flavi- and enterovirus infections in mice were studied. differential enhancement of mortality rates after extraneural and, less markedly, intracerebral virus inoculation was noted. while depression of humoral and/or cell-mediated immunity is considered to be responsible for the effects observed in flavivirus infections, impaired function of the reticuloendothelial system seems to contribute main ...1975172474
poly(a) on mengovirus rna.the content and size of the poly(a) on mengovirus rna grown in both mouse l cells and hela cells have been examined. virion rna from either cell line could bind to poly(u) filters and contained rnase-resistant stretches of poly(a) which could be analyzed by electrophoresis in polyacrylamide gels. the size of the poly(a) on the mengovirus rna was independent of the host cell and averaged from 50 to 70 nucleotides.1975170414
a model for the hepatitis b virus core protein: prediction of antigenic sites and relationship to rna virus capsid proteins.the sequences of the core proteins from several serotypes of human hepatitis b virus and related mammalian and avian hepadnaviruses are aligned with the vp3 capsid protein of mengo virus, a picornavirus. the homology indicates an eight-stranded antiparallel beta-barrel fold for the hepatitis protein, as observed in the tertiary structure of the picornavirus protein. the locations of known antigenic sites and other modifications are consistent with this structure for the core protein. the predict ...19882456212
the isolation of mengo virus stable non-capsid polypeptides from infected l cells and preliminary characterization of an rna polymerase activity associated with polypeptide e.isolation of the mengo virus stable non-capsid virus polypeptides e, f, g and i from infected l cells has been achieved. unstable precursors were eliminated by incubation in the presence of pactamycin and capsid polypeptides were removed by ultracentrifugation and affinity chromatography. subsequent sodium dodecyl sulphate (sds)-hydroxylapatite chromatography resolved the non-capsid proteins into two major peaks which comprised f plus g and e plus i, respectively. the individual polypeptide spec ...1979230290
pathogenicity of mengo virus to mice. iii. potentiation of infection by immunosuppressants.mengo virus has been described to cause, in dependence on the virus dose, lethal panencephalomyelitis and exocrine pancreatitis in mice after i.p. inoculation. two immunosuppressive agents, cyclophosphamide and 1,3-bis(piperidinomethyl)-5-ethyl-5-phenyl-barbituric acid (zimet 176/68), were shown to potentiate mengo virus infection as demonstrated by histopathology and enhanced mortality. organotropism of mengo virus did not change under the drug treatment. however, the histological lesions in br ...1979228963
trichomonas vaginalis resistance to mengo virus infection.we have investigated the susceptibility of trichomonas vaginalis to mengo virus infection by comparing the outcome of mengo virus or purified mengo virus rna infection in t. vaginalis and in ccl-1 mouse fibroblasts. while the adsorption and entry of mengo virus into t. vaginalis occurred in the same manner as in fibroblasts, the uncoating was much slower. in addition, mengo virus infection of t. vaginalis displayed no eclipse nor any subsequent production of infectious virus. purified rna failed ...1979226694
studies of two temperature-sensitive mutants of mengo virus.studies of the synthesis of viral ribonucleates and polypeptides in cells infected with two rna- ts mutants of mengo virus (ts 135 and ts 520) have shown that when ts 135 infected cells are shifted from the permissive (33 degrees c) to the nonpermissive (39 degrees c) temperature: (i) the synthesis of all three species of viral rna (single stranded, replicative form, and replicative intermediate) is inhibited to about the same extent, and (ii) the posttranslational cleavage of structural polypep ...1979224989
translational control: recognition of the methylated 5' end and an internal sequence in eukaryotic mrna by the initiation factor that binds methionyl-trnafmet.structural analogs of the methylated 5' end (cap) of eukaryotic mrna, such as 7-methylguanosine 5'-monophosphate, specifically inhibit both gtp-dependent binding of met-trnafmet and binding of globin mrna to eukaryotic initiation factor 2 (eif-2). addition of purified eif-2 effectively relieves the cap analog-induced inhibition of globin mrna translation. the analog competitively inhibits the function of eif-2 and of mrna in protein synthesis. binding to eif-2 of capped mrna as well as noncapped ...1978273228
[use of direct calorimetry for continuously following the course of experimental infections in the mouse].to obtain information about early symptoms of infection measurements of heat production were performed in experimentally infected animals. as a model mengo virus-infected mice were used. construction and physical properties of the flow calorimeter device are described. fever was not detected by method used. however, deviations from normal behaviour of the animals were demonstrated as a result of the relationship between motoric activity and heat produced. furthermore, the method may be particula ...19892551106
inhibition of ribonucleases by ribonucleotides and transition state analogs in cell-free extracts from ehrlich ascites tumor cells.we investigated the ribonucleolytic breakdown of poly(u), poly(a), rna trascribed from calf thymus dna with e. coli rna polymerase, ribosomal rna, trna and mengovirus rna by an enzyme fraction obrained from a postribosomal supernatant of ehrlich ascites tumor cells. the single-stranded homopolyribonucleotides are preferentially degraded by the enzyme fraction with the production of ribonucleoside 5'-monophosphates. the rnase activity is completely dependent on the presence of mg2+ ions and is hi ...1977324884
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