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selective reduction of insulin mrna in islets infected with encephalomyocarditis virus. 19902177410
protein synthesis initiation factor modifications during viral infections: implications for translational control.infection of tissue culture cells with certain viruses results in the shutoff of host cell protein synthesis. we have examined virally infected cell lysates using two-dimensional gel electrophoresis and immunoblotting to ascertain whether initiation factor protein modifications are correlated with translational repression. moderate increases in eukaryotic initiation factor (eif)-2 alpha phosphorylation are detected in reovirus- and adenovirus-infected cells, as reported previously (samuel et al. ...19902188834
recombinant equine interferon-beta 1: purification and preliminary characterization.equine interferon-beta 1 (eqifn-beta 1) was purified from extracts of recombinant escherichia coli by sequential chromatography on hydroxylapatite, anion-, and cation-exchangers. the resulting protein was greater than 98% pure as determined by sodium dodecylsulfate gel electrophoresis, gel permeation hplc, and reverse-phase hplc. amino-terminal amino acid sequencing revealed that essentially all molecules contained an additional amino-terminal methionine. the specific antiviral activity of eqifn ...19902200832
cytoplasmic expression system based on constitutive synthesis of bacteriophage t7 rna polymerase in mammalian cells.a mouse cell line that constitutively synthesizes the bacteriophage t7 rna polymerase was constructed. fluorescence microscopy indicated that the t7 rna polymerase was present in the cytoplasmic compartment. the system provided, therefore, a unique opportunity to study structural elements of mrna that affect stability and translation. the in vivo activity of the bacteriophage polymerase was demonstrated by transfection of a plasmid containing the chloramphenicol acetyltransferase (cat) gene flan ...19902204064
theiler's murine encephalomyelitis virus--characterization of newly isolated viruses from japanese mouse colonies.the hemagglutinating-inhibition (hi) test was used to detect antibodies for theiler's murine encephalomyelitis virus (tmev), and the virus was isolated from sero-positive mice derived from colonies in japan. hi antibody was detected in conventional mice (38.7%; 137/354) at titers ranging from 1:8 to 1:512, but it not in spf mice (0/90). to isolate the virus, weanling mice inoculated intracerebrally with samples obtained from sero-positive mice were sacrificed and 10% brain homogenates were subcu ...19902242766
mildiomycin: a nucleoside antibiotic that inhibits protein synthesis.mildiomycin, a new nucleoside antibiotic, selectively inhibits protein synthesis in hela cells, and is less active in the inhibition of rna or dna synthesis. an increased inhibition of translation by mildiomycin is observed in cultured hela cells when they are permeabilized by encephalomyocarditis virus. this observation suggests that this antibiotic does not easily pass through the cell membrane, as occurs with other nucleoside and aminoglycoside antibiotics. the inhibition of translation is al ...19852409064
analogue inhibitor of 2-5a action: effect on the interferon-mediated inhibition of encephalomyocarditis virus replication.chemically synthesised ch3sp(a2'p)2a2'pp3'och3 has been used to assess the importance of the ppp(a2'p)na (n greater than or equal to 2: 2-5a) system in the antiviral action of interferon against encephalomyocarditis virus (emc). it inhibits activation of the 2-5a-dependent rnase by 2-5a in intact mouse l929 cells and cell-free systems. in interferon-treated, emc-infected l929 cells it inhibits 2-5a-mediated rrna cleavage and partially restores emc rna synthesis and virus yield. activation of the ...19852410258
monoclonal antibodies as structural probes for oligomeric human interferon-gamma.monoclonal antibodies (mab) b1 and b3, specific for human interferon-gamma (ifn-gamma) failed to immunoprecipitate heat-inactivated human ifn-gamma in solution. however, both mab retained some reactivity with denatured ifn-gamma immobilized on vinyl plates. the two mab have been employed in a sensitive immunoradiometric assay (irma). in this irma one mab was bound to polystyrene beads and used as immunoadsorbent. the second mab, labeled with 125i, was used as the tracer to quantitate the amount ...19852414374
antiviral activity of prostaglandin a on encephalomyocarditis virus-infected cells: a unique effect unrelated to interferon.antiviral effects of prostaglandins of the a series (pgas) on sendai, vaccinia and vesicular stomatitis viruses have previously been reported and a relationship between the antiviral actions of pgas and interferons has been suggested. we have investigated the antiviral activity of pgas on encephalomyocarditis (emc) virus. using single-cycle assays of virus replication our results indicate that pgas only inhibit when present in the culture medium after the cells are infected, and that they are mo ...19852414395
antiviral and antiproliferative effects of interferons in quiescent fibroblasts are dissociable.quiescent mouse swiss 3t3 cells or human fibroblasts treated with interferon for only 2 hr before the addition of serum are effectively protected against virus infection for up to 24 hr after the addition of serum and the removal of interferon. in sharp contrast, exposure of quiescent fibroblasts to interferon only before addition of serum or the peptides epidermal growth factor and insulin, has no inhibitory effect on cell proliferation. further, even when interferon is added after the addition ...19852416119
[interferonogenicity of the bacterial lysates in human and murine cell cultures].the antibacterial jrs vaccine was found to be capable of inducing interferon production in human peripheral blood leukocytes and mouse bone marrow cells. the vaccine induced no interferon in l-929 cells or human diploid m-19 cells. interferon appeared in the culture fluid within 4-6 hours after induction and reached the maximum levels in 18-24 hours. one-hour contact of the vaccine with leukocytes was sufficient for interferon induction. the interferon generated in human blood leukocytes was par ...19852420072
levels of 2',5'-oligoadenylates in the tissues of pathogen-free mice.2',5'-oligoadenylate (2-5a) has been reported to exist in a variety of cells and tissues. since it has been suggested that these compounds play a role in normal cell metabolism as well as in the interferon response, we sought to determine the levels of 2-5a in healthy mouse tissue. methodology developed to recover 2-5a from tissue included tca extraction, fractionation on silica and and c18 cartridges and hplc. the 2-5a content in hplc fractions was determined by an enzyme-linked immunoassay. th ...19852421302
studies on interferon-sensitive cells derived from the interferon-resistant nih 3t3 clone 1 line.from the nih 3t3 clone 1 line which is normally unprotected by interferon (ifn) against lytic virus infection we have selected subclones which show high sensitivity to ifn. the selection procedure was based on encephalomyocarditis virus (emcv) as selection agent. in the ifn-sensitive subclones thus obtained emcv replication was inhibited by ifn to a similar degree as observed in l929 cells. like in the original nih 3t3 clone 1 line, however, replication of vesicular stomatitis virus (vsv) and ce ...19852421304
the 2-5a system in control and interferon-treated k/balb cells infected with encephalomyocarditis virus. 19852421309
immunochemistry, physical chemistry and biology of 2',5'-oligoadenylates.monoclonal antibodies directed against 2-5a were developed and characterized. 2',5'-oligoadenylate-protein complexes possess at least three distinct antigenic surfaces defined primarily by the ribose-phosphate backbone. a schematic model for the three epitopes is presented. antibodies directed against 2-5a, in conjunction with other techniques, were employed to quantify 2-5a in various tissues of pathogen-free mice. levels of 2-5a were in the range of 400-800 fmole/gm. mice injected with poly(i) ...19852421316
vaccinia-mediated rescue of encephalomyocarditis virus from the inhibitory effects of interferon.coinfection of mouse l cells with vaccinia virus rescues encephalomyocarditis virus (emc) from the inhibitory effect of interferon (ifn). the vaccinia-mediated rescue of emc growth increases the yield of emc as much as 1000-fold and is optimum when vaccinia is used at a multiplicity of infection of 1. this rescue correlates with a vaccinia-dependent stimulation of emc gene expression. evidence is presented to indicate that the rescue by vaccinia does not involve a block of the 2'-5'a synthetase ...19862424172
the inhibition of nucleic acid synthesis in encephalomyocarditis virus-infected l929 cells: effects on nucleoside transport.picornavirus infection induces a profound inhibition of labelling of newly synthesized rna in some cell lines. emc virus blocks transcription in l929 cells, particularly at early times during infection. this inhibition is not dependent on virus gene expression, since it occurs with uv-inactivated virus and also in the presence of translation inhibitors. the inhibition can be largely accounted for by the blockade of [3h]nucleoside transport, as suggested by the transport kinetics and incorporatio ...19862425245
potentiation by levamisole, methisoprinol, and adenine or adenosine of the inhibitory activity of human interferon against encephalomyocarditis virus.the antiviral action of different human interferons against encephalomyocarditis virus in hela cell cultures was analyzed. cell treatment with levamisole (200 micrograms/ml), methisoprinol (1 mg/ml), or adenine or adenosine (33 or 100 micrograms/ml, respectively) potentiated the anti-encephalomyocarditis virus activity of human interferon by 8- to 32-fold. a higher level of potentiation (256-fold) was achieved either by combined treatments with levamisole plus methisoprinol or by treatment with ...19862428301
effect of encephalomyocarditis (emc) virus on murine foetal and placental growth monitored by quantification of maternal plasma levels of pregnancy-associated murine protein-2 and alpha-fetoprotein.the present study demonstrates that pregnant mice seem to be more sensitive to encephalomyocarditis (emc) infection than non-pregnant mice, and the infection results in significantly increased maternal plasma levels of insulin and pregnancy-associated murine protein-2 (pamp-2), of placental origin, and alpha-fetoprotein (afp), of foetal origin. maternal plasma levels of pamp-2 and afp are correlated with placental and foetal growth respectively. this indicates that the emc infection and the incr ...19862431595
antigen-specific suppressor t cells prevent cardiac injury in balb/c mice infected with a nonmyocarditic variant of coxsackievirus group b, type 3.two variants of coxsackievirus group b, type 3 (cvb3o and cvb3m) infect balb/c cardiac tissue equally, but only one variant (cvb3m) induces myocarditis. various studies indicate that disease resistance in cvb3o-infected mice results from generation of suppressor cells. low-dose cyclophosphamide (50 mg/kg body weight) treatment enhances inflammation in both cvb3m and cvb3o-infected animals, which clearly demonstrates that cvb3o has the capacity to induce disease, but inhibitory factors must exist ...19862432792
trypanosoma brucei rhodesiense infection in mice prevents virus-induced diabetes: possible role of interferon and immunological mechanisms.b10.br, dba/2, and balb/c by j mice were infected with trypanosoma brucei rhodesiense (lou tat clone 1). subsequent infection with the d variant of encephalomyocarditis virus (emc-d) resulted in no diabetes or encephalitis, even in the susceptible dba/2 and balb/c by j strains. low levels of circulating interferon (ifn) were detected in trypanosome-infected mice at the time of emc-d infection. all strains were severely immunosuppressed as a result of trypanosome infection, as evidenced by decrea ...19862433362
loss of (2'-5')oligoadenylate synthetase activity by production of antisense rna results in lack of protection by interferon from viral infections.an expression vector was constructed that carries part of the human bk papovavirus with 0.5 kilobases of (2'-5')oligoadenylate (2-5a) synthetase cdna inserted in inverted orientation downstream from the virion proteins (vp) promoter and the neomycin-resistance gene neo under the control of a simian virus 40 promoter. cells transfected with this vector and selected for resistance to the neomycin derivative g418 synthesized rna complementary to 2-5a synthetase mrna. these cells lacked 2-5a synthet ...19872433688
[comparative study of interferon inducers obtained from natural sources].interferon-inducing and antiviral effects of natural dsrna preparations of phage phi 6 and yeast cells were studied in the culture of murine cells l-929 and on random bred albino mice. both the preparations showed interferon inducing activity in the cell culture. however, for realization of their effect modification of the surface cell membrane by polycation exchange resin (deae-dextran) was required. the interferon-inducing activity of both of the natural dsrna in the mice was high. the maximum ...19872436574
accumulation of 2',5'-oligoadenylates in encephalomyocarditis virus-infected mice.levels of 2',5'-oligoadenylates (2-5a) in various tissues of murine encephalomyocarditis virus (emcv)-infected mice were determined and compared with those found in pathogen-free mice and in mice treated with the interferon inducer poly(i).poly(c). in control, pathogen-free mice, liver, spleen, brain, and kidney tissues possessed levels of 2-5a below 1 pmol/g of tissue, demonstrating that 2-5a was not a major component of uninfected mouse tissue. all control tissues had low basal levels (0.3 to ...19872437319
antigenic comparison of the polypeptides of foot-and-mouth disease virus serotypes and other picornaviruses.the cross-reactivity of proteins coded for by the seven serotypes of foot-and-mouth disease virus (fmdv) was assessed by reaction of infected cell lysates with polyclonal and monospecific antisera against the structural and nonstructural proteins of fmdv type a12 strain 119ab. it was shown that the homologous polypeptides from most serotypes are antigenically related. the least cross-reactivity occurred between vp1, vp3, and the protease (3c) of type a12 and south african territories types 1 and ...19872437694
the influence of high temperature on human cells in culture, their sensitivity to viruses and their interferon-producing capacity.the influence of extremely high temperatures on the course of virus infection in vitro was studied. it has been shown that exposure of human cells (continuous cell line of embryonal skin-muscle tissue, donor blood leukocytes) to 43 degrees c leads to a significant increase in their sensitivity to cytopathic action of the viruses tested. noteworthy, the reproduction of these viruses under tested conditions did not differ from their reproduction in control cells. a dramatic inhibitory effect of hi ...19872437783
helper-inducer t-lymphocytes mediate diabetes in emc-infected balb/c byj mice.diabetes mellitus developing in balb/c byj mice infected with the m variant of encephalomyocarditis (emc) virus is dependent on thymic immune mechanisms. we treated mice with the anti-t-lymphocyte monoclonal anti-l3t4 and anti-lyt2.2 antibodies before virus inoculation and monitored the infection and occurrence of diabetes thereafter. mice depleted of l3t4+ cells exhibited a reduced incidence and severity of diabetes compared with both untreated and anti-lyt2.2-treated animals. all mice sustaine ...19872438180
class ii-restricted t cell responses in theiler's murine encephalomyelitis virus (tmev)-induced demyelinating disease. i. cross-specificity among tmev substrains and related picornaviruses, but not myelin proteins.following intracerebral inoculation of theiler's murine encephalomyelitis virus (tmev), susceptible mouse strains develop a chronic demyelinating disease characterized by mononuclear cell-rich infiltrates in the central nervous system. current evidence strongly supports an immune-mediated basis for myelin breakdown, with an effector role proposed for tmev-specific, major histocompatibility class ii-restricted delayed-type hypersensitivity, which temporally correlates with disease onset and remai ...19872438327
sensitivity of human germ-cell-tumor cell lines to human interferons.we examined the sensitivity of four human germ-cell-tumor cell lines exhibiting different stages of differentiation to human interferons (ifns) in vitro. the cell lines were derived from two embryonal carcinomas (nec 8 and nec 14), a choriocarcinoma (ima), and a yolk-sac tumor (huot). treatment with poly i:c induced ifn production in ima and huot cells, but not in nec-8 and nec-14 cells. in the two embryonal-carcinoma cell lines, the addition of ifn-alpha, ifn-beta, and ifn-gamma did not prevent ...19872439404
rapid decrease in the levels of the double-stranded rna-dependent protein kinase during virus infections.the double-stranded rna-dependent protein kinase from human cells is a 68,000 molecular weight protein (p68 kinase), the level of which is enhanced significantly in cells treated with interferon. with a monoclonal antibody specific for p68 kinase, here we show the phosphorylation and steady-state levels of p68 kinase during virus infection. the p68 kinase is phosphorylated in interferon-treated cells during infection with encephalomyocarditis virus (emcv), vesicular stomatitis virus (vsv), and v ...19872440179
role of interferon, antibodies and macrophages in the protective effect of corynebacterium parvum on encephalomyocarditis virus-induced disease in mice.treatment of mice with corynebacterium parvum enhances their resistance to encephalomyocarditis (emc) virus infection. in emc-virus-infected mice, pretreated with c. parvum, neither interferon production nor antibody responses were increased. a decrease of virus recovery was observed in cultures of macrophages taken from the peritoneum of mice early after injection of c. parvum and infected with emc-virus in vitro. the data suggest that c. parvum acts by increasing intrinsic antiviral activity o ...19872440381
interferon induces a 15-kilodalton protein exhibiting marked homology to ubiquitin.immunochemical methods were used to examine the effect of viral infection on the dynamics of intracellular ubiquitin pools. infection of either the human lung carcinoma line a-549 or the mouse fibroblast line l929 with encephalomyocarditis virus had little effect on either the distribution or fractional level of intracellular ubiquitin conjugates. in contrast, viral infection resulted in a significant decline in the steady state content of the mono-ubiquitin conjugate to histone 2a (uh2a). prior ...19872440890
interferon inducibility and sensitivity of human teratocarcinoma-derived cell lines.three cell lines tera i, tera ii, and pa1, derived from human teratocarcinomas were tested for their capacity to produce interferon (ifn) and for their sensitivity to both human ifn-alpha and ifn-beta. when treated with newcastle disease virus or sendai virus, or a synthetic polyribonucleotide, poly(ri):poly(rc), tera i cells produced no ifn and the 2',5'-oligoadenylate (2-5a) synthetase enzymatic pathway was not activated, although there was an increase in protein kinase. in contrast, tera ii a ...19872440957
clonal derivatives of the rd-114 cell line differ in their antiviral and gene-inducing responses to interferons.the human rhabdomyosarcoma cell line rd-114 is partially responsive to interferons (ifns). in these cells, alpha interferon (ifn-alpha) or gamma interferon (ifn-gamma) inhibits the replication of some viruses but not of others. similarly, some of the ifn-inducible mrnas are induced poorly, whereas others are induced well. here we report the isolation of clonal derivatives of this line which display different spectra of responses to ifns. among the eight extensively characterized clonal lines, on ...19872441075
selection and characterization of interferon-sensitive cells derived from an interferon-resistant nih 3t3 line.we have developed a selection protocol to isolate interferon (ifn)-sensitive subclones directly from an ifn-resistant cell population. the protocol uses encephalomyocarditis virus (emcv) as a selection agent in combination with pretreatment with low doses of ifn and subsequent growth in the presence of virus-neutralizing antiserum. we have applied this protocol to the partially ifn-resistant nih 3t3 clone 1 line and have obtained a number of ifn-sensitive subclones. sensitivity to ifn was restri ...19872445907
tunicamycin enhances virus replication and inhibits antiviral activity of interferon in mice: correlation with natural killer cells.earlier we reported that tunicamycin (tm) treatment enhances semliki forest virus (sfv) and encephalomyocarditis virus (emcv) replication in swiss mice. interferon (ifn) mediated antiviral protection was also inhibited in mice treated with tm. the in vitro natural killer (nk) cell reactivity of mice was significantly decreased after in vivo administration of tm; however, tm treatment did not affect the response of the same cells to mitogens. tm also inhibited the boosting of nk reactivity by ifn ...19872445942
antibody-nucleic acid interactions. antibodies to psoralen-modified rna as probes of rna structure.antisera elicited by immunization of rabbits with 4'-aminomethyl-trioxsalen (amt)-modified poly(a,u) complexed with methylated bovine serum albumin was characterized in competition radioimmunoassays (ria) and enzyme-linked immunosorbent assays (elisa). amt-poly(a,u) was over 10,000-fold more reactive than unmodified poly(a,u) or amt alone. the antiserum cross-reacted to varying extents with amt-modified-rna's and -dna's. the presence of amt-uridine usually assured strong reactivity. the amino gr ...19872446261
physical dependence to morphine diminishes the interferon response in mice.morphine pellet implantation in mice was demonstrated to diminish resistance to encephalomyocarditis virus infections. the variations in the response to three different interferon (ifn) inducers--newcastle disease virus, escherichia coli lipopolysaccharide and a tilorone analogue--were evaluated. a close relationship between morphine dependence and ifn response was detected. a clear inhibition in ifn induction appeared as a concomitant phenomenon with the syndrome of morphine dependence. in the ...19872448267
antiviral effects of recombinant human tumor necrosis factor.the antiviral action of recombinant human tumor necrosis factor (tnf) was studied using assay systems to determine inhibition of viral cytopathic effect (cpe), as well as suppression of virus growth measured by plaque assays. tnf was cloned and prepared by asahi chemical industry, japan. antiviral activity against human herpes simplex virus (hsv) types 1 and 2, cytomegalovirus (cmv), varicella-zoster virus (vz), vesicular stomatitis virus (vsv) and encephalomyocarditis virus (emc), was demonstra ...19872448553
[potentiation of the antiviral activity of human interferons by virazole in in vitro experiments].combination of interferon and virazole results in potentiation of their antiviral activity. this was demonstrated with all three types of natural interferons and the recombinant rl-2-interferon. this effect is retained at a temperature of 37 degrees c and increases when the chemical drug is combined with a mixture of alpha- and gamma-interferon.19872448957
a fast and sensitive method for detecting specific viral rna in mammalian cells.a quick and sensitive method to quantitate viral rna synthesis has been developed. utilizing glutaraldehyde to fix infected cells onto nitrocellulose paper, viral rna can be probed directly in situ. viral message can be detected from as few as 10(4) infected cells. this technique can be used to study viral gene expression and can be adapted to screen the activity of antiviral agents such as interferon.19882450208
hiv-1-specific production of ifn-gamma and modulation by recombinant il-2 during early hiv-1 infection.specific cellular immune responses to human immunodeficiency virus type 1 (hiv-1) were assessed in mononuclear leukocyte cultures from homosexual men with documented, early phase hiv-1 infection. cell cultures from men with a mean duration of 1.3 yr (range, 0.3 to 2.2 yr) of hiv-1 infection were treated with uv-inactivated, whole, purified hiv-1 ag together with various concentrations of ril-2. cell supernatants were harvested after 5-day incubation and assayed for ifn activity against encephalo ...19882452186
inhibition of transcription of herpes simplex virus immediate early genes in interferon-treated human cells.the effect of interferon (ifn) treatment on the early stages of herpes simplex virus type 1 (hsv-1) replication in three types of human cells was investigated. interferon pretreatment was shown to reduce the steady state levels of both total and polysomebound hsv-1 immediate early alpha mrnas. using the nuclear run-off transcription assay, we showed that ifn selectively inhibited transcription of the hsv-1 genes, with no effect on transcription of total cellular rna or that of the beta-tubulin r ...19882455018
the interaction of interferon-alpha and -gamma: regulation of (2-5)a synthetase activity.the interaction of ifn-alpha and ifn-gamma on the induction of antiviral, growth inhibitory, and (2-5)a synthetase activities was investigated in t98g and a549 cells. synergistic or inhibitory effects which were host-cell dependent were seen with both simultaneous and sequential ifn treatments. interestingly, ifn-gamma 1 pretreatment affected the levels of ifn-alpha-induced (2-5)a synthetase activity differently in the two cell types. in t98g cells, sequential treatment resulted in an overall de ...19882455384
isolation and characterization of interferon-resistant variants from s49 mouse lymphoma.s49 mouse lymphoma cells were found to be extremely sensitive to the antiproliferative activity of interferon. these characteristics were studied to select for ifn-resistant cell variants. some 0.6% of the parental s49 cell population were resistant to the antiproliferative and cytotoxic activities of ifn. the resistant cells were cloned and analyzed for their responses to several of the activities of ifn, namely, inhibition of encephalomyocarditis (emc) virus, murine leukemia virus (mulv) repli ...19882455652
discrimination of determinant specificity of two encephalomyocarditis virus neutralizing monoclonal antibodies by competition, mixed neutralization and anti-idiotypic antibodies.to investigate the epitope(s) on encephalomyocarditis virus (emcv) involved in neutralization, two neutralizing monoclonal antibodies (mas) (ma um 21.1 and ma um 21.2) were tested in a competition binding assay (cba), a mixed neutralization test and an enzyme immunoassay (eia) with specificity for the detection of idiotypes on mas. with a cba in cell culture, using emcv infected l cell monolayers as binding antigen, strong homologous competition was observed between unlabelled mas and horse radi ...19882456299
distinct domains of recombinant human ifn-gamma responsible for anti-viral effector function.a panel of 21 independently isolated neutralizing mab directed against the human rifn-gamma (rhuifn-gamma) was used to characterize those epitopes that are involved in the antiviral function of the rhuifn-gamma. a sandwich competition assay was developed to determine the cross-reactivities between the mab. the 125i-labeled mab were allowed to compete with varying amounts of unlabeled mab for binding to rhuifn-gamma under ag-limiting conditions, and the 50% inhibition endpoints were determined fo ...19882459212
coxsackievirus b-3-induced myocarditis. virus and actinomycin d treatment of myocytes induces novel antigens recognized by cytolytic t lymphocytes.balb/c mice inoculated with 6 x 10(4) plaque-forming units of a myocarditic variant of coxsackievirus, group b, type 3 (cvb3m) developed three distinct ctl populations recognizing putative virion (virus specific ctl, vctl), normally expressed heart (autoreactive ctl, actl), and aberrant metabolic (mctl) ag. induction of the mctl-specific ag on cardiocytes correlated with the ability of the myocarditic viruses and actinomycin d to interfere with cellular metabolism as measured by 3h-uridine and 3 ...19882459248
[effect of inhibitors that destroy cytoskeleton structures on the antiviral and antiproliferative activity of interferons].the effect of a number of drugs (vincristine, vinblastine, cytochalasin b, colcemid, colchamine) destroying cytoskeleton structures (microtubules and microfilaments) in combination with homologous interferon was studied in l920 and caov cells. the above substances were shown to inhibit the antiviral and enhance (from additivity to synergism) the antiproliferative effect of interferons under study.19882459850
enhancement of viral pathogenesis in mice maintained in an antiorthostatic suspension model: coordination with effects on interferon production.both rodents and men returning from spaceflight and the attendent microgravity or weightlessness conditions have exhibited alterations in immune responses and, in particular, interferon production. we have utilized a model for antiorthostatic (20 degrees head-down tilt). hypokinetic, hypodynamic suspension of mice that simulates some aspects of weightlessness. female swiss/webster mice that are normally resistant to infection with the d variant of encephalomyocarditis virus showed a marked incre ...19872461049
[effect of virus-induced interferon on mast cell resistance to the degranulating action of immune complexes].regularities of endogenous interferon (ifn) induction with newcastle disease virus (ndv) in rats and the effect of this process of the resistance of mast cells to the degranulating effect of immune complexes are described. increased resistance of mast cells to the damaging effect of immune complexes for 72 hours after a single induction of endogenous ifn with virus was demonstrated in experiments in vivo. inoculation of rats with ndv treated at ph = 2.0 did not induce the production of endogenou ...19882464242
effect of interferons and poly(i):poly(c) on the pathogenesis of the diabetogenic variant of encephalomyocarditis virus in different mouse strains.interferon (ifn) can either prevent or exacerbate the pathogenic effects of the diabetogenic variant of encephalomyocarditis (emc-d) virus. the effect seen is dependent upon the mouse strain and the time of ifn administration. for example, ifn-alpha beta protects swr/j but not icr swiss male mice against the diabetogenic effects of the virus. administration of either ifn-alpha beta or the ifn-inducer poly(i):poly(c) 4 days post infection, results in an exacerbation of the infection in icr swiss ...19882466089
properties of interferons produced by different cell populations. 19882469281
inhibited interferon production after space flight.several studies have been performed in our laboratories indicating that interferon production may be impaired in rodents after space flight. using an antiorthostatic suspension model that simulates some of the effects of microgravity seen during space flight, we have shown that interferon-alpha/beta production was inhibited. the inhibition was not due solely to the stress of suspension. the inhibited interferon production was transient, as suspended animals returned to normal caging recovered th ...19882469283
interferon production by the preimplantation sheep embryo.ovine trophoblast protein-1 (otp-1), the major product secreted by the trophectoderm of the sheep conceptus between days 13 and 21 of pregnancy, is considered to mediate maternal recognition of pregnancy by maintaining the function of the corpus luteum. its amino acid sequence has 40-55% identity with various mammalian interferons-alpha (ifn-alpha), and it has been shown to have antiviral activity. the present results confirm that otp-1, which at days 15-17 of pregnancy is produced by a single e ...19892469745
[interferonogenic activity of low-molecular compounds of plant origin]. 19882470203
the antiviral activity of tumor necrosis factor in hela cells is not mediated by interferons. studies with tnf-resistant variants.tumor necrosis factor (tnf) has a relatively modest antiviral activity in hela cells, when compared to that of interferon (ifn). addition of antisera neutralizing ifn-alpha or beta did not reduce the antiviral activity of tnf. furthermore, we determined with a sensitive hybridization assay that less than one molecule of ifn-beta 1 mrna could be present per tnf-treated cell. hela cell variants resistant to the tnf cytocidal activity were selected. these variants had tnf receptors with a dissociat ...19882474237
rapid bioassay of human interferon by direct enzyme immunoassay of encephalomyocarditis virus in hep-2 cell monolayers after a single cycle of infection.multiplication of encephalomyocarditis virus (emcv) in human hep-2 cells, and its suppression by interferon (ifn), was demonstrated by direct enzyme immunoassay (eia) in cell culture. emcv was detected in glutaraldehyde fixed hep-2 cell monolayers, in wells of 96-well plates, with a horse radish peroxidase (hrpo) labelled emcv specific monoclonal antibody. multiplication of emcv (multiplicity of infection: 50) was indicated by a steep rise of absorbance values measured against infected monolayer ...19892474560
differing attachment of diabetogenic and nondiabetogenic variants of encephalomyocarditis virus to beta-cells.the d variant of encephalomyocarditis (emc-d) virus does not induce the production of interferon (ifn) and produces an insulin-dependent diabetes mellitus (iddm)-like syndrome in certain mouse strains. in contrast, the b variant (emc-b) virus, which is serologically identical to emc-d virus, is a good inducer of ifn and is nondiabetogenic. it has been postulated that ifn may play a major role in determining the ability of these two viruses to infect pancreatic beta-cells. however, recent studies ...19892475377
competition binding assay in cell culture for identification of epitopes on enveloped and naked viruses.virus infected monolayers, in wells of 96-well plates, could be used as antigen in competition binding assays to identify epitopes on respectively semliki forest virus, encephalomyocarditis virus and mumps virus.19892476138
antisense oligonucleotide inhibition of encephalomyocarditis virus rna translation.we report the inhibition of encephalomyocarditis virus (emcv) rna translation in cell-free rabbit reticulocyte lysates by antisense oligonucleotides (13-17-base oligomers) complementary to (a) the viral 5' non-translated region, (b) the aug start codon and (c) the coding sequence. our results demonstrate that the extent of translation inhibition is dependent on the region where the complementary oligonucleotides bind. non-complementary and 3'-non-translated-region-specific oligonucleotides had n ...19892476310
murine cell-mediated immune response recognizes an enterovirus group-specific antigen(s).splenocytes taken from mice inoculated with coxsackievirus b3 (cvb3) (nancy) developed an in vitro proliferative response against cvb3 antigen. this response could not be detected earlier than 8 days postinoculation but could be detected up to 28 days after exposure to cb3. cvb3-sensitized splenocytes responded not only to the cvb3 antigen but to other enteroviruses as well. this response was found to be enterovirus specific in that no response was detected to a non-enteroviral picornavirus, enc ...19892476566
constitutive expression of a 2',5'-oligoadenylate synthetase cdna results in increased antiviral activity and growth suppression.the interferon (ifn)-induced enzyme 2',5'-oligoadenylate (2-5a) synthetase has been implicated in the development of antiviral activity in human and animal cells. however, its role in ifn-mediated growth inhibition remains unclear. to elucidate the function of 2-5a synthetase, we have stably introduced a human 2-5a synthetase cdna into a human glioblastoma cell line (t98g). constitutive expression of the cdna in these cells is associated with increased levels of resistance to infection by enceph ...19892481699
the role of interferon in the protection of icr swiss male mice by the nondiabetogenic variant of encephalomyocarditis virus against virus-induced diabetes mellitus.the production of murine diabetes mellitus by the diabetogenic variant of encephalomyocarditis virus (emcv-d) is prevented in mice preinfected for 24 h with nondiabetogenic virus (emcv-b). it has been suggested that the protection of the animals is due to the induction of interferon (ifn) by emcv-b. the present study was done to investigate further the role of ifn in the protection of male icr swiss mice against the diabetogenic effects of emcv-d virus. the results show that this mouse strain is ...19892481700
influence of flavonoids on combined experimental infections with emc virus and staphylococcus aureus in mice.activity of elected flavonoids in emc virus and staphylococcus aureus infected mice were investigated, to determine the influence on mortality rate. some of the flavonoids: quercetin, hypoletin, hesperidin, rutin and quercitrin showed significant protective effect given before single as well as combined viral-bacterial infections.19892482663
different antiviral activity and cell specificity of interferon preparations produced by mouse peritoneal cells at 37 degrees c and at 26 degrees c.three sublines of mouse l cells and mouse embryo fibroblasts were used for determination of the antiviral activity of mouse interferons produced by nonadherent peritoneal exudate cells incubated either at 37 degrees c or at 26 degrees c. ifn produced at 37 degrees c or at 26 degrees c had the same antiviral activity in l borgen, l929 cells. however, in mec ifn-37 degrees had relatively higher activity than ifn-26 degrees. of the interferon investigated only ifn-37 degrees exhibited antiviral act ...19892484831
experimental encephalomyocarditis virus infection in mongolian gerbils (meriones unguiculatus).two strains of mongolian gerbils (meriones unguiculatus), tumble brook (tum) and japan medical science (jms), were intraperitoneally inoculated with the d variant of encephalomyocarditis virus (emc-d) and killed 3 days later. mortality was significantly higher in females than in males. evidence of viral replication was detected in the heart of both strains and in the pancreas of the tum strain. histopathological alterations were found in the heart and pancreas. heart lesions involved foci of nec ...19892536510
myocardial uptake of antimyosin monoclonal antibody in a murine model of viral myocarditis.the myocardial uptake of 125i- and 131i-antimyosin monoclonal antibody fab in experimental myocarditis in balb/c mice induced by encephalomyocarditis virus was studied. the biodistribution of 125i-antimyosin demonstrated that the highest ratio of radioactivity appears in the heart of infected mice on day 14 (the ratio of percent dose per gram for the organ to percent dose per milliliter for blood; 9.75 +/- 2.79 vs. 1.27 +/- 0.78 at 24 hours in inoculated mice vs. control mice). there was no stat ...19892536600
proteolytic cleavage of encephalomyocarditis virus capsid region substrates by precursors to the 3c enzyme.picornavirus protease 3c is normally released from its p3 precursor by two successive self-cleavage reactions. the free enzyme can then catalyze most of the remaining processing events within the viral polyprotein. to investigate the role of the 3c precursors in the processing cascade, we constructed cdna clones which expressed genetically altered forms of the encephalomyocarditis p3 region in vitro. site-specific substitutions were introduced into the gln-gly residues at the 3b-3c and 3c-3d jun ...19892536819
molecular identification of diabetogenic viral gene.the best evidence that viruses have a causative role in the pathogenesis of insulin-dependent diabetes mellitus comes from experiments in mice infected with encephalomyocarditis (emc) virus. when sjl/j male mice were inoculated with a highly diabetogenic emc-d virus, diabetes developed in 95% of the animals. in contrast, none of the mice inoculated with a nondiabetogenic emc-b virus became diabetic. tissue culture experiments showed that emc-b induces considerable amounts of interferon, whereas ...19892537245
initiation of protein synthesis by internal entry of ribosomes into the 5' nontranslated region of encephalomyocarditis virus rna in vivo.expression vectors that yield mono-, di-, and tricistronic mrnas upon transfection of cos-1 cells were used to assess the influence of the 5' nontranslated regions (5'ntrs) on translation of reporter genes. a segment of the 5'ntr of encephalomyocarditis virus (emcv) allowed translation of an adjacent downstream reporter gene (cat) regardless of its position in the mrnas. a deletion in the emcv 5'ntr abolishes this effect. poliovirus infection completely inhibits translation of the first cistron ...19892538648
cloning and synthesis of infectious cardiovirus rnas containing short, discrete poly(c) tracts.mengovirus rna transcripts with 5' noncoding poly(c) tracts of c8, c12, and c13uc10 have been synthesized in vitro from cdna clones and shown to be infectious to hela cells. a chimeric clone has also been constructed which links the 5' end from one mengovirus clone (299 nucleotides, containing c13uc10) to a 7,424-base fragment derived from the 3' end of encephalomyocarditis (emc) virus. progeny virus isolated after transfection with the clone-derived rnas had the same poly(c) tracts, mengovirus- ...19892538661
viral myocarditis: immunopathogenesis and the effect of immunosuppressive treatment in a murine model.serial changes in lymphocyte subset were investigated in an animal model of encephalomyocarditis (emc) virus myocarditis in mice. the lymphocyte subset in the peripheral blood was measured by flow cytometry and, t cell subset in the myocardium was stained by labeled avidin-biotin technique. helper-inducer t cells (lyt 1 cells) decreased significantly on day 7, but there was no change in cytotoxic-suppressor t cells in the peripheral blood. during the acute stage a significant number of t cells ( ...19892541264
genomic differences between the diabetogenic and nondiabetogenic variants of encephalomyocarditis virus.plaque purification of the m variant of encephalomyocarditis (emc-m) virus resulted in the isolation of two stable variants. one is a highly diabetogenic d variant (emc-d) and the other is a nondiabetogenic b variant (emc-b). the cdna of emc-d and emc-b genomes were cloned and seven overlapping cdna clones were selected to cover the entire genome except the 5'-end 310 bases which were determined by rna-dependent dna sequencing and enzymatic rna sequencing. each clone was restriction-mapped, subc ...19892541543
production and in vivo biologic actions of recombinant mouse interferon alpha 2.we have expressed a recombinant mouse interferon alpha (r.mu-ifn alpha 2) in escherichia coli under the control of a tryptophan promoter using a synthetic adaptor formed by annealing two partially complementary oligonucleotides which introduced an atg start codon and re-established the complete coding sequence of the mature ifn alpha 2 protein in the expression vector. levels of up to 10(7) reference units of mu-ifn alpha 2 per liter of culture were obtained using this construction. this recombi ...19892544081
viral myocarditis and cardiomyopathy. 19892544753
di-octyl phthalate induced altered host resistance: viral and protozoal models in mice. 19892545652
reduced activity of the interferon-induced double-stranded rna-dependent protein kinase during a heat shock stress.previous studies have shown that the antiviral response induced by interferon in murine cells could be degraded after a heat shock. here we have confirmed that a similar effect occurs also in interferon-treated human hela cells subjected to a heat shock. in addition, we have investigated the fate of the interferon-induced, double-stranded rna-dependent protein kinase in heat-shocked cells. this protein kinase is a mr 68,000 protein (p68 kinase) which, when autophosphorylated, catalyzes phosphory ...19892545700
a serologic survey of encephalomyocarditis virus infection in pigs in italy.neutralizing antibodies to encephalomyocarditis virus (emcv) were found in 69.13% of the serum samples obtained from pigs from representative regions of italy. the antibodies are distributed fairly uniformly throughout the swine populations with all age groups being equally involved.19892546020
human infection with encephalomyocarditis virus in new south wales. 19892547141
[changes in the myocardium in encephalomyocarditis of pigs].the myocardial lesions of pigs (age from 2.5 to 3.5 month) with encephalomyocarditis virus infection are presented. the disease is caused by members of the genus cardiovirus (family picornaviridae). in greece it was first observed 1987 in two stables of pig-breeders with a mortality of 80%. the macroscopic changes are characterized by a myocardial degeneration with greyish pale linear or round foci and by an accumulation of a clear red to yellow fluid in the pericardium and the pleural cavity. t ...19892547556
conservation of the secondary structure elements of the 5'-untranslated region of cardio- and aphthovirus rnas.an analysis of published nucleotide sequences of the 5'-untranslated region (5'-utr) of 7 cardioviruses and 3 aphthoviruses has allowed us to derive a consensus secondary structure model that differs from that previously proposed for the 5'-utr of entero- and rhinoviruses, though all these viruses belong to the same family, picornaviridae. the theoretical model derived here was experimentally supported by investigating the accessibility of encephalomyocarditis virus rna to modifications with dim ...19892548167
cap-independent translation of mrna conferred by encephalomyocarditis virus 5' sequence improves the performance of the vaccinia virus/bacteriophage t7 hybrid expression system.a recombinant vaccinia virus that directs the synthesis of bacteriophage t7 rna polymerase provides the basis for the expression of genes that are regulated by t7 promoters in mammalian cells. the t7 transcripts, which account for as much as 30% of the total cytoplasmic rna at 24 hr after infection, are largely uncapped. to improve the translatability of the uncapped rna, the encephalomyocarditis virus (emcv) untranslated region (utr) was inserted between the t7 promoter and the chloramphenicol ...19892548200
regulation of macrophage growth and antiviral activity by interferon-gamma.interferons, in addition to their antiviral activity, induce a multiplicity of effects on different cell types. interferon (ifn)-gamma exerts a unique regulatory effect on cells of the mononuclear phagocyte lineage. to investigate whether the antiviral and antiproliferative effects of ifn-gamma in macrophages can be genetically dissociated, and whether ifn-alpha and ifn-gamma use the same cellular signals and/or effector mechanisms to achieve their biologic effects, we have derived a series of s ...19892549078
an unusual coordinated cleavage event in the processing of encephalomyocarditis virus polypeptides.during the translation of encephalomyocarditis virus rna in the rabbit reticulocyte lysate system, polypeptides 2b and 2c, encoded by the central region of the genome, appear simultaneously in the absence of any detectable 2bc precursor and at a time when translation has advanced into the region coding for polypeptide 3c. this implies the operation of closely coordinated proteolysis at two sites, with at least one cleaved by the virus-coded protease activity 3c.19892549719
tumor necrosis factor acts synergistically with autocrine interferon-beta and increases interferon-beta mrna levels in human fibroblasts.medium of untreated human fs-4 foreskin fibroblasts contained a factor which, upon the addition of exogenous tumor necrosis factor (tnf), inhibited encephalomyocarditis virus replication when neither medium alone nor tnf alone were effective. this antiviral activity was abolished by a monoclonal antibody to human interferon (ifn)-beta, suggesting that the active component in the medium from untreated fs-4 cells was ifn-beta, present at subeffective concentrations. in addition, we show that untre ...19892550437
treatment of encephalomyocarditis virus-induced central nervous system demyelination with monoclonal anti-t-cell antibodies.infection of balb/c mice with the m variant of encephalomyocarditis virus resulted in the development of a paralytic syndrome in 7 to 10 days. the paralysis was maximal during the period of viral clearance; most of the animals recovered from the initial deficit and showed no delayed recurrences. pathologically, the white matter of brain and spinal cord showed well-demarcated areas of perivascular cuffing, demyelination, and, during recovery, remyelination by oligodendrocytes--all suggestive of p ...19892550666
identification and production of monoclonal antibodies against a discriminating protein molecule between b and d variants of encephalomyocarditis virus.the protein profiles of two emc virus variants b and d in the infected l929 fibroblast lysates were examined using one- and two-dimensional gel electrophoresis. both variants yielded a protein molecule of similar molecular weight but differing in its isoelectric point (pi). the b variant lysate yielded a molecule with pi congruent to 7.5 whereas the same molecule from the d lysate focused at pi congruent to 5.2. a monoclonal antibody (mca) produced against pi congruent to 5.2 fraction of the d v ...19892551748
degradation of cellular proteins during poliovirus infection: studies by two-dimensional gel electrophoresis.picornaviruses encode for their own proteinases, which are responsible for the proteolytic processing of the polyprotein encoded in the viral genome to produce the mature viral polypeptides. the two poliovirus proteinases, known as proteins 2a and 3c, use the poliovirus-encoded polyprotein as a substrate. the possibility that these poliovirus proteinases also degrade cellular proteins remains largely unexplored. high-resolution two-dimensional gel electrophoresis indicates that a few cellular pr ...19892552149
susceptibility of four species of small rodents to encephalomyocarditis (emc) virus infection.the d variant of encephalomyocarditis virus (10(1)-10(5) pfu/head) was intraperitoneally inoculated into 4 species of small rodents, rats, mice, syrian hamsters, and mongolian gerbils, and the susceptibility of these animals to emc virus was examined virologically and histopathologically 3 days after infection. viral replication was detected in the brain (mice), in the heart (mice and gerbils), and in the pancreas (mice, hamsters, and gerbils). no viral replication was detected in rats. histopat ...19892553452
anti-interferon antibodies to interferon-alpha 2b: results of comparative assays and clinical perspective.previous studies have reported a low (less than 3%) incidence of anti-interferon (ifn) serum neutralizing antibodies following treatment with ifn-alpha 2b. since this result contrasts with a higher incidence reported with ifn-alpha 2a, the question has been raised whether differences in assay techniques and patient comparability rather than inherent differences in the molecules might account for the reported differences in antibody incidence. in this report two patient groups, 151 hairy cell leu ...19892553829
hydrolysis of a series of synthetic peptide substrates by the human rhinovirus 14 3c proteinase, cloned and expressed in escherichia coli.the 3c proteins of several picornaviruses, including poliovirus, foot-and-mouth disease virus (fmdv) and encephalomyocarditis virus (emcv), have been demonstrated to be cysteine-type proteinases, involved in the processing of the respective polyproteins expressed by the monocistronic rna genome. nucleotide sequencing data have indicated that the human rhinovirus 14 (hrv-14) rna genome encodes a homologous 3c protein. the hrv-14 3c protein was purified to homogeneity from escherichia coli express ...19892555433
tropism and histopathology of the d, b, k, and mm variants of encephalomyocarditis virus.variants of encephalomyocarditis virus (emcv), which are immunologically indistinguishable by hyperimmune serum, produce different disease syndromes in mice. for instance, in icr swiss male mice, emcv-b produces no overt illness, emcv-mm produces severe neurological signs followed by death, emcv-d destroys pancreatic beta cells producing a disease syndrome resembling insulin-dependent diabetes mellitus, and emcv-k is lethal but produces no overt signs of infection. the present study was done to ...19892555446
inducible expression of encephalomyocarditis virus 3c protease activity in stably transformed mouse cell lines.an inducible expression vector system has been developed to facilitate the study of the effects of individual virus gene products on cell function. the vector utilizes the mouse metallothionein promoter carried on the bovine papillomavirus genome. conditions which optimize the induced expression of open reading frames inserted downstream from the mouse metallothionein promoter have recently been described. in this communication we describe the use of this system to clone and express the encephal ...19892555538
pathogenic properties of encephalomyocarditis virus isolates in swine fetuses.the pathogenicity of 5 different encephalomyocarditis (emc) virus isolates was investigated in swine fetuses following injection of each virus in utero. laparotomies were performed on 3 pregnant sows in early mid-third (39-40 days) of gestation and on 5 sows in the late mid-third (70-72 days) of gestation, and groups of fetuses were inoculated with different viruses into the amniotic sacs. the uninoculated fetuses served as controls. thirty-five (71.4%) of 49 infected and 1 of 26 control fetuses ...19892558630
sex-dependent, early cytokine production by nk-like spleen cells following infection with the d variant of encephalomyocarditis virus (emcv-d).spleen cell cultures from diabetes-resistant icr swiss females exhibited an increase in expression of ia antigens 24 hours post-infection (pi) with emcv-d while comparable spleen cell cultures from diabetes-susceptible males of this strain did not exhibit this increase in ia antigens expression. a monoclonal antibody specific for mouse interferon-gamma (ifn gamma) eliminated this increase in ia antigens expression. interferon-gamma (ifn gamma) and interleukin 2 (il-2) production by emcv-d-infect ...19892560916
serologic, virologic, and histopathologic observations of encephalomyocarditis virus infection in mummified and stillborn pigs.stillborn and mummified swine fetuses from swine farms experiencing reproductive problems were investigated for evidence of infection with encephalomyocarditis (emc) virus by fetal serology, virus isolation, and histopathologic examination. fetal sera or thoracic fluids of 478 abnormal fetuses collected during january through december 1987 were tested for the presence of antibody specific to emc virus. of 478 samples tested, 175 (36.6%) had emc virus serum neutralizing antibody titers of 1:64 or ...19892562190
serological survey for viral diseases in the cayo santiago rhesus macaque population.the free-ranging population of rhesus monkeys (macaca mulatta) on cayo santiago was sero-surveyed for human measles, simian virus 40, b virus (herpes simiae), rhesus cytomegalovirus, human and simian retroviruses and encephalomyocarditis virus to determine the prevalence of these viruses in the colony. the results of this study indicate that the colony is free of sv40, htlviii (hiv-1), stlviii (siv) and srv1; has a low prevalence of measles and emcv; and high prevalence rates for b virus, cmv an ...19892571176
the preparation of antiidiotypic antibodies against human beta-interferon. 19892576603
role of sex and early interferon production in the susceptibility of mice to encephalomyocarditis virus.adult female swiss mice showed a greater resistance to intraperitoneal (i.p.) infection with encephalomyocarditis virus (emcv) than male mice. this difference was not observed in weanling mice, in castrated adult mice or in adult mice injected intracerebrally. administration of antibody to mouse interferon alpha/beta enhanced the virulence of emcv for both sexes and no difference was then observed in susceptibility between male and female mice. six h after emcv infection, serum interferon titres ...19852580047
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