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mutational analysis of the encephalomyocarditis virus primary cleavage.sixteen substitution mutations of the conserved dvexnpgp sequence, implicated in cardiovirus and aphthovirus primary polyprotein cleavage, were created in encephalomyocarditis virus cdna, expressed, and characterized for processing activity. nearly all the mutations severely decreased the efficiency of the primary cleavage reaction during cell-free synthesis of viral precursors, indicating a stringent requirement for the natural sequence in this processing event. when representative mutations we ...19968794329
enhancement by muramyl peptides of the protective response of interferon-alpha/beta against encephalomyocarditis virus infection.the use of interferon-alpha (ifn-alpha) in the treatment of infectious diseases has shown limited efficacy and dose-limiting toxicity. we have selected safe immunomodulators of the muramyl peptide family with the potential of enhancing the efficacy of ifn-alpha without resulting in increased toxicity. one of these synthetic muramyl dipeptide (mdp) derivatives, namely murabutide which is in a clinical stage of development, has been recently found to synergize with ifn-alpha 2a in the selective in ...19968796446
the immunogenic and pathogenic potential of short poly(c) tract mengo viruses.we have shown previously that genetically engineered mengo viruses with artificial deletions in their 5' noncoding polyribocytidylic acid (poly(c)) tracts are highly attenuated for the natural murine host and also for other animals such as baboons, macaques, and domestic pigs. the present report further characterizes select short poly(c) tract mengo viruses in the natural murine host. a positive correlation was found between the length of the poly(c) tract and murine virulence, as measured by vi ...19968806569
expression of intracellular interferon constitutively activates isgf3 and confers resistance to emc viral infection.the mechanism(s) by which interferon (ifn)-alpha confers resistance to viruses is currently being characterized. previous studies have shown that binding of ifn-alpha to its high-affinity receptor activates transcription factor interferon-stimulated gene factor 3 (isgf3), which positively regulates a number of antiviral genes including 2'-5'-oligoadenylate synthetase (2-5a synthetase). we show that mouse l cells expressing nonsecreted (intracellular) type i human ifn are less susceptible to ence ...19968836915
activity of nitric oxide-generating compounds against encephalomyocarditis virus.nitric oxide (no) generated by two no donors (sodium nitroprusside or s-nitroso-l-glutathione) was shown to exert a dose-dependent inhibition of encephalomyocarditis virus growth in l-929 cells. this activity was not due to the cytotoxic or direct virucidal effects of no donors. l-929 cells were shown to produce no endogenously, but this low level of production did not counter encephalomyocarditis virus replication.19968849231
protection of non-murine mammals against encephalomyocarditis virus using a genetically engineered mengo virus.genetically engineered mengo viruses with artificial deletions in the 5' noncoding poly(c) tracts are highly attenuated for pathogenicity when introduced as live vaccines into the natural murine host. inoculation produces lifelong protective immunity without disease or viral persistence. this report extends the vaccination studies to non-murine hosts, including baboons, macaques and domestic pigs, all of which are susceptible to severe cardiovirus epizootics. all animals of these species that we ...19968852413
improved dicistronic mrna expression vectors for efficient selection of transfectants highly expressing foreign genes. 19968879573
a murine rna polymerase i promoter inserted into the herpes simplex virus type 1 genome is functional during lytic, but not latent, infection.the development of herpes simplex virus as a vector for neuronal gene delivery is dependent upon the identification and characterization of promoter elements capable of driving long-term expression during latency. the majority of rna polymerase ii (pol ii) promoters studied are active during acute infection but silenced during latency. in order to investigate the potential of a murine rna polymerase i (pol i) promoter to drive reporter gene expression during lytic and latent infection, we descri ...19968887493
systematic evaluation of chimeric marker genes on dicistronic transcription units for regulated expression of transgenes in vitro and in vivo.plasmid expression vectors combining human cytokine cdnas and selectable marker genes on dicistronic transcription units were functionally characterized in vitro and in vivo. the internal ribosome entry sequence (ires) of encephalomyocarditis virus mediated cap-independent translation of the downstream cistron. after cationic lipofection of cells with a dicistronic construct containing the neor gene downstream of a human interleukin-2 (il-2) cdna, all g418-resistant clones secreted high amounts ...19968894674
variation in serum creatine phosphokinase activity as indicated in two-phase emc-d virus-induced myocarditis.in this study, myocardial damage in the d-variant of encephalomyocarditis (emc-d) virus-induced myocarditis has been investigated consecutively by measuring serum creatine phosphokinase (cpk) activity. cpk activity in 8 week-old male balb/cajcl mice inoculated with emc-d virus increased to a peak at 4 or 5 days postinoculation (dpi) and then gradually decreased. the cpk activity rose again after 7 dpi until it reached a second peak. in view of the kinetics of cpk activity, two-phase (early and l ...19968902496
construction of adenoviral and retroviral vectors coexpressing the genes encoding the hepatitis b surface antigen and b7-1 protein.recombinant retroviral (re-rv) and adenoviral (re-ad) vectors for delivery of two foreign genes were constructed, using the internal ribosomal entry site (ires) of encephalomyocarditis virus (emcv) which mediates initiation of cap-independent translation. the first gene encoded the hepatitis b surface antigen (hbsag) and the second encoded human or murine b7-1 molecule, a cell surface protein which is a costimulator for t cell activation. the emcv ires sequence was placed between the first and s ...19968917087
engineered disulfide bonds in recombinant human interferon-gamma: the impact of the n-terminal helix a and the ab-loop on protein stability.insertion sites for cysteines with optimal stereochemistry for the formation of unstrained disulfide bridges were identified in recombinant human interferon-gamma (rhu-ifn-gamma) by computer modelling. we have engineered two different disulfide cross-linked mutants, containing a pair of symmetry-related disulfide bonds, which stabilize the n-termini of both monomers of the homodimeric protein. mutations e7c and s69c allow the formation of an intramonomer disulfide bond between helices a and d. i ...19968931130
protecting fibrinogen with rutin during uvc irradiation for viral inactivation.fibrinogen solutions were irradiated with uvc (254 nm) to inactivate contaminating viruses. in order to protect fibrinogen during uvc irradiation, 0.5 mm rutin was added prior to uvc exposure and subsequently removed during processing. viral kill by 0.1 j/cm2 uvc resulted in the following inactivation values (log 10): non-lipid-enveloped viruses: parvo > or = 5.5; encephalomyocarditis virus > or = 6.5; hepatitis a virus > or = 6.5: lipid-enveloped viruses: human immunodeficiency virus > or = 5.7 ...19968934767
overexpression of human prothrombin in permanent cell lines using a dominant selection/amplification fusion marker.human prothrombin was overexpressed in transformed eukaryotic cells using a dominant bifunctional selection and amplification marker. the marker consists of the murine wild-type dihydrofolate reductase (dhfr) cdna and the escherichia coli hygromycin phosphotransferase gene fused in frame. the gene of interest is connected by the encephalomyocarditis virus 5' untranslated region to the fusion marker gene, forming a dicistronic transcription unit. the human prothrombin gene (fii) was used to monit ...19968936598
antiviral nonspecific immunity of human placenta at term: possible role of endogenous tumor necrosis factors and interferons.the antiviral immunity of human placenta and amniotic membrane in an organ culture (oc) system was studied. freshly isolated explants of most of the placentas at term and the amniotic membranes were found to be relatively resistant to herpes simplex virus type 1 (hsv-1), encephalomyocarditis virus (emcv), and vesicular stomatitis virus (vsv) infections. after in vitro aging, however, the oc acquired the sensitivity to the viruses. in about 66%-90% of placentas, resistance of freshly isolated exp ...19968938570
persistent expression of cytokine in the chronic stage of viral myocarditis in mice.dilated cardiomyopathy (dcm) is one of the most frequent causes of heart failure of unknown origin. one possible cause of dcm is considered to be a sequel to myocarditis. however, the mechanism of progression from viral myocarditis to dcm is still not clear.19968941123
canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry.translation of picornavirus rna is initiated after ribosomal binding to an internal ribosomal entry site (ires) within the 5' untranslated region. we have reconstituted ires-mediated initiation on encephalomyocarditis virus rna from purified components and used primer extension analysis to confirm the fidelity of 48s preinitiation complex formation. eukaryotic initiation factor 2 (eif2), eif3, and eif4f were required for initiation; eif4b and to a lesser extent the pyrimidine tract-binding prote ...19968943341
functional dissection of eukaryotic initiation factor 4f: the 4a subunit and the central domain of the 4g subunit are sufficient to mediate internal entry of 43s preinitiation complexes.eukaryotic translation is initiated following binding of ribosomes either to the capped 5' end of an mrna or to an internal ribosomal entry site (ires) within its 5' nontranslated region. these processes are both mediated by eukaryotic initiation factor 4f (eif4f), which consists of eif4a (helicase), eif4e (cap-binding protein), and eif4g subunits. here we present a functional analysis of eif4f which defines the subunits and subunit domains necessary for its function in initiation mediated by th ...19968943342
ires bicistronic expression vectors for efficient creation of stable mammalian cell lines.stable transfection of mammalian cells is a widely used technique for the study of gene expression and protein purification. however, selection of cell lines expressing desired genes from a large number of candidate clones is often labor-intensive and time consuming. to improve the efficiency of stable cell line production, we have used a bicistronic mammalian expression vector, pires1hyg, which contains the internal ribosome entry site (ires) of the encephalomyocarditis virus (ecmv). the ires e ...19968954121
mouse macrophages carrying both subunits of the human interferon-gamma (ifn-gamma) receptor respond to human ifn-gamma but do not acquire full protection against viral cytopathic effect.studies of hamster-human and mouse-human somatic fibroblast hybrids and transfected mouse fibroblasts have demonstrated that signaling through the human interferon-gamma receptor (hu-ifn-gammar) requires the formation of a complex consisting of ligand (ifn-gamma), a ligand binding receptor chain (ifn-gammar1), and a signal transducing receptor chain (ifn-gammar2). to date, the ability of this receptor complex to transduce the full repertoire of biological signals has been difficult to assess due ...19968955096
rapamycin stimulates viral protein synthesis and augments the shutoff of host protein synthesis upon picornavirus infection.the immunosuppressant drug rapamycin blocks progression of the cell cycle at g1 in mammalian cells and yeast. we recently showed that rapamycin inhibits both in vitro and in vivo cap-dependent, but not cap-independent, translation. this inhibition is causally related to reduced phosphorylation and consequent activation of 4e-bp1, a repressor of the function of the cap-binding protein, eif4e. two members of the picornavirus family, encephalomyocarditis virus and poliovirus, inhibit phosphorylatio ...19968971030
mengo virus 3c proteinase: recombinant expression, intergenus substrate cleavage and localization in vivo.mengo virus 3c proteinase was cloned and expressed to high levels in a bacterial vector system. the protein was solubilized from inclusion bodies then purified to homogeneity (> 95%) by ion exchange chromatography. the recombinant enzyme was proteolytically active in cell-free processing assays with a mengo capsid precursor substrate, l-p1-2a, correctly and proficiently cleaving it into l, 1ab, 1c, 1d and 2a protein products. further analyses with synthetic peptide substrates encompassing the me ...19968972564
diabetic animal models.insulin-dependent (type 1) diabetes is a frequent disease with an incidence of up to about 1%. it requires daily treatment and serious late complications are observed. good animal models exist for studying diabetes. these can be categorized as animals with spontaneously developing diabetes (bb rats, nod mice) and as animals with induced diabetes (e.g. by virus). immunodeficient nude mice have also been widely used. none of the models is perfect, but each has contributed to our present knowledge ...19968972684
structural analysis of the interaction of the pyrimidine tract-binding protein with the internal ribosomal entry site of encephalomyocarditis virus and foot-and-mouth disease virus rnas.initiation of translation of a subset of eukaryotic mrnas results from internal ribosomal entry. this process is exemplified by encephalomyocarditis virus (emcv), which contains an internal ribosomal entry site (ires) within its 5' nontranslated region that is approximately 450-nt long and consists of a series of stem-loops designated h-l. we have previously identified a cellular 58-kda polypeptide that binds specifically to this ires and that is implicated in its function as the pyrimidine trac ...19968972770
the intracellular domain of the second chain of the interferon-gamma receptor is interchangeable between species.in this report we show that the mouse interferon (ifn)-gamma r1 and ifn-gamma r2 subunits expressed in hamster cells are capable of rendering the cells sensitive to mouse ifn-gamma as measured by induction of class i mhc antigens and the activation of the transcription factor stat1 alpha. however, these cells showed no antiviral protection in response to ifn-gamma when challenged with vesicular stomatitis virus (vsv) but limited protection when challenged with encephalomyocarditis virus (emcv). ...19968974007
regulated expression of the interferon-induced protein kinase p68 (pkr) by vaccinia virus recombinants inhibits the replication of vesicular stomatitis virus but not that of poliovirus.a direct antiviral role of the interferon-induced human protein kinase p68 has been shown only against encephalomyocarditis virus (emcv) and vaccinia virus (vv). to determine if p68 kinase (pkr) has a broad antiviral effect, we have used coinfections between vv recombinants expressing p68 kinase under regulation of the lac i operator/repressor elements of escherichia coli and two rna viruses, vesicular stomatitis virus (vsv) and poliovirus. in cells coinfected with vv recombinants and vsv, induc ...19968974011
characterization of the nuclear localization signal and subcellular distribution of hepatitis c virus nonstructural protein ns5a.hepatitis c virus (hcv) has a positive strand rna genome that codes for a polyprotein that is processed co-translationally and post-translationally into three structural and at least seven nonstructural (ns) proteins. to investigate the function of ns5a, a recombinant vaccinia virus was constructed in which the ns5a gene was cloned under the control of t7 promoter and encephalomyocarditis virus 5'-untranslated region (emcv-utr) for cap-independent translation in mammalian cells. in addition, the ...19968982089
beneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis. a possible mechanism through inhibition of nitric oxide production.although calcium channel blockers have not been shown to be beneficial for the treatment of patients with heart failure, a recent clinical trial demonstrated a favorable effect of amlodipine on the survival of patients with heart failure resulting from nonischemic dilated cardiomyopathy. we investigated the effects of amlodipine on a murine model of congestive heart failure induced by the m variant of encephalomyocarditis virus (emcv).19978994443
complementation of defective picornavirus internal ribosome entry site (ires) elements by the coexpression of fragments of the ires.mutant forms of the encephalomyocarditis virus (emcv) internal ribosome entry site (ires) have been produced and shown to be severely defective in directing internal initiation of protein synthesis within cells using the vaccinia/t7 rna polymerase system. mutants in different regions of the ires were complemented in trans by coexpression of the intact emcv ires but not by coexpression of the related ires elements from theiler's murine encephalomyelitis virus (another cardiovirus) or from foot-an ...19979007058
immunological defects in mice with a targeted disruption in bcl-3.the proto-oncogene bcl-3 is a member of the ikappab family. the bcl-3 protein is known to interact specifically with the p50 and p52 subunits of nfkappab. however, the function of this interaction is not well understood. to determine the in vivo role of bcl-3, mice were generated that lack the bcl-3 gene, bcl 3(-/-). here we report that bcl 3(-/-) mice appear developmentally normal, but exhibit severe defects in humoral immune responses and protection from in vivo pathogenic challenges. relative ...19979009202
the cleavage activities of aphthovirus and cardiovirus 2a proteins.the primary 2a/2b polyprotein cleavage of aphtho-and cardioviruses is mediated by their 2a proteins cleaving c-terminally. whilst the aphthovirus 2a region is only 16 aa (possibly 18 aa) long, the cardiovirus 2a protein is some 150 aa. we have previously shown that foot-and-mouth disease virus (fmdv) 2a is able to mediate cleavage in an artificial (chloramphenicol acetyltransferase/fmdv 2a/beta-glucuronidase [cat-2a-gus]) polyprotein system devoid of any other fmdv sequences with high (approxima ...19979010280
survey for antibodies to selected viruses in laboratory mice in south africa.serum samples (n = 184) from 3 conventional laboratory mouse colonies were tested for antibodies with an indirect fluorescent antibody (ifa) test to theiler's murine encephalomyelitis virus (tmev), encephalomyocarditis virus (emcv), and reovirus type 3. the percentage of mice with antibodies to reovirus type 3, were comparable in all 3 groups, namely 40, 46 and 60%. antibodies to tmev showed the greatest variation, namely 0, 10 and 31%, whereas antibodies to emcv were confirmed in only one colon ...19909022849
detection of viral rna by electron microscopic in situ hybridization (ish-em) in the germinal epithelium of mice infected with encephalomyocarditis (emc) virus.electron microscopic in situ hybridization (ish-em) was first applied to the detection of viral rna in the germinal epithelium of mice inoculated i.p. with 10(5) plaque-forming units/mouse of the d variant of encephalomyocarditis virus (emc-d). signals of viral rna were first detected in a small number of sertoli cells showing mild degeneration at 2 days post inoculation, and 2 days later, they were also detected in germinal cells and spermatogonia when sertoli cells showed prominent degeneratio ...19979027476
wst-1 assay--a simple colorimetric method for virus titration. 19979028831
a new translational regulator with homology to eukaryotic translation initiation factor 4g.translation initiation in eukaryotes is facilitated by the cap structure, m7gpppn (where n is any nucleotide). eukaryotic translation initiation factor 4f (eif4f) is a cap binding protein complex that consists of three subunits: eif4a, eif4e and eif4g. eif4g interacts directly with eif4e and eif4a. the binding site of eif4e resides in the n-terminal third of eif4g, while eif4a and eif3 binding sites are present in the c-terminal two-thirds. here, we describe a new eukaryotic translational regula ...19979049310
suppression of high mobility group protein t160 expression impairs mouse cytomegalovirus replication.the high mobility group (hmg-1) box proteins bind both non-b-dna conformations and specific nucleotide sequences. they have been implicated in a wide variety of cellular functions involving dna, such as transcription, replication and recombination. to determine whether hmg-1 box protein t160 plays a role in virus replication, we employed an antisense strategy to inhibit its expression in nih 3t3 cells. the two t160 clones that expressed levels of t160 50% lower than those expressed by clones tra ...19979049420
effect of amrinone on murine viral myocarditis.management of acute viral myocarditis is still controversial. amrinone, a noncatecholamine nonglycoside bipyridine agent, produces sustained improvement of cardiac function and symptomatology in congestive heart failure (chf). amrinone demonstrates phosphodiesterase inhibitory activity that is relatively selective for the major phosphodiesterase isozyme in cardiac muscles, pde iii, which specifically hydrolyzes cyclic 3'5' adenosine monophosphate (camp). we investigated the effects of amrinone i ...19979055349
utilization of the herpes simplex virus type 1 latency-associated regulatory region to drive stable reporter gene expression in the nervous system.the ability of herpes simplex virus type 1 (hsv-1) to establish a lifelong, transcriptionally active, latent infection in neurons has led to much interest in developing hsv-based vectors for gene delivery to the nervous system. a prerequisite of such vectors is that they should be capable of directing long-term transgene expression in latently infected neurons. the continued transcription of hsv-1 latency-associated transcripts (lats) during neuronal latency suggests that regulatory sequences wh ...19979060683
virucidal treatment of blood protein products with uvc radiation.the virus safety of blood derivatives continues to be of concern, especially with respect to nonenveloped and/or heat-stable viruses. previously, we demonstrated that treatment of whole plasma, ahf concentrate or fibrinogen with short wavelength ultraviolet light (uvc) results in the inactivation of > or = 10(6) infectious doses (id) of encephalomyocarditis virus (emcv), hepatitis a virus (hav) and porcine parvovirus (ppv), each of which is nonenveloped. protein recovery was enhanced greatly by ...19979077126
inactivation of hepatitis a and other enteroviruses during heat treatment (pasteurization). 19969088550
possible role of macrophage-derived soluble mediators in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice.pancreatic islets from dba/2 mice infected with the d variant of encephalomyocarditis (emc-d) virus revealed lymphocytic infiltration with moderate to severe destruction of pancreatic beta cells. our previous studies showed that the major population of infiltrating cells at the early stages of infection is macrophages. the inactivation of macrophages prior to viral infection resulted in the prevention of diabetes, whereas activation of macrophages prior to viral infection resulted in the enhance ...19979094680
the poly(c) region affects progression of encephalomyocarditis virus infection in langerhans' islets but not in the myocardium.the diabetogenic variant pv2 of encephalomyocarditis virus was cloned, and three recombinants differing in their 5' poly(c) tracts were analyzed. it is shown that the poly(c) region is not essential for infectivity in mice but does influence the virus load and degree of pathological lesions within the langerhans' islets but not in the myocardium.19979094698
relation between stable glycated hemoglobin a1c and plasma glucose levels in diabetes-model mice.in an iddm model mouse which was inoculated with a diabetogenic variant, dk-27, of encephalomyocarditis (emc) virus, the relation between a stable glycated hemoglobin a1c (st-hba1c) level and plasma glucose level (pgl) in the progress of diabetes was studied. the st-hba1c level and pgl were examined every 2 weeks for 10 weeks in normal male dba/2 and iddm-onset mice. pgls of normal control mice did not change, but their st-hba1c levels were slightly increased by 0.52 to 1.03%. on the other hand, ...19979145293
transmissibility of murine stem cell virus-based retroviral vectors carrying both interleukin-12 cdnas and a third gene: implications for immune gene therapy.the combination of immunotherapy with conventional treatments such as radio- and chemotherapy may be necessary to eradicate minimal residual disease. interleukin 12 (il-12) is a heterodimeric cytokine composed of two subunits, p40 and p35. coordinate expression of the il-12 p40 and p35 genes in several solid tumor models has been found to induce strong and specific antitumor immune responses. in the interest of obtaining high level il-12 expression in leukemia/lymphoma cells for use as vaccines ...19979171935
distinct antigenic subtypes of human beta interferon can be distinguished by neutralization.different molecular configurations of human beta interferon were titrated with the standard reference antiserum of the national institutes of health (nih) which had been prepared with natural beta fibroblast interferon in order to determine to what extent differences in these configurations would influence the neutralization of the antiviral action of interferon. neutralization tests were carried out in vero cells by diluting both interferon and antiserum. encephalomyocarditis virus was employed ...19969181103
in vivo expression of an interferon-alpha gene by intramuscular injection of naked dna.acid-stable type i interferons belong to a multigene family. the biologic relevance of each subtype in vivo remains unknown. we have developed an experimental model in which muscles were transfected in situ with naked dna plasmids encoding an ifn transgene to assess the roles of individual ifn subtypes in vivo. murine ifn-alpha 9 gene was subcloned into several mammalian expression vectors. adult c57bl/6 mice were injected bilaterally in regenerating tibialis anterior muscles with naked dna 5 da ...19979181463
interaction of truncated human interferon gamma variants with the interferon gamma receptor: crucial importance of arg-129.recombinant human interferon gamma (ifn-gamma), produced in escherichia coli, was selectively truncated at its c-terminus with chymotrypsin, clostripain or plasmin. the c-terminal amino acid residues of the three truncated ifn-gamma variants were identified as phe136, arg129 and lys128, indicating the removal of 7, 14 and 15 amino acid residues from the full-length molecule. the absence of seven c-terminal residues did not influence the binding of ifn-gamma to its receptor. in contrast, the trun ...19979182722
susceptibility to virus infection is determined by a stat-mediated response to the autocrine effect of virus-induced type i interferon.interferon (ifn) signalling appears to be the predominant pathway that leads to the development of the host defence against virus. however, other mechanisms that are ifn independent may also be involved. the stat1 transcription factor is specific for the ifn pathway and plays a central role in mediating many, if not all, ifn-dependent biological responses. viral infection of cells in the presence or absence of stat1 was studied to examine the role of ifn-dependent and independent antiviral mecha ...19979199872
an age-related change in susceptibility of rat brain to encephalomyocarditis virus infection.rats were inoculated intraperitoneally (i.p.) or intracerebrally (i.c.) with 1 x 10(4) plaque forming units (pfu)/animal of the d variant of encephalomyocarditis virus (emc-d) at 2, 4, 7, 14, 28 or 56 days of age for virological and histopathological examination. in the i.p.-inoculation study, neither viral replication nor lesions were detected in the animals inoculated at 28 and 56 days of age. in the animals inoculated when younger than 14 days of age, lesions were restricted to the brain alth ...19979203984
interleukin-8 selectively enhances cytopathic effect (cpe) induced by positive-strand rna viruses in the human wish cell line.interleukin-8 (il-8), a proinflammatory chemokine, is induced by viruses and appears in circulation during viral infections. we found that il-8 enhanced cytopathic effect induced by the positive strand rna virus, encephalomyocarditis virus (emcv), in the human wish cell line. the enhancement was dependent on il-8 dose and virus dose and was reversible by specific monoclonal antibodies to il-8. the chemokine was also able to increase emc viral rna synthesis and infectious virus yield. this il-8 e ...19979207237
viral susceptibility of a newly established cell line derived from the peritoneal cavity of balb/c mouse.viral susceptibility of a newly established cell line, named kmp, derived from the peritoneal cavity of balb/c mouse is described. the cells were originally cloned from the in vitro culture of ascites of the mouse injected with ehrlich ascitic tumor cells in advance. the electrophoretic pattern of cellular dnas, extracted from kmp, normal balb/c mouse spleen, and ehrlich tumor cells respectively were compared after triple digestions with restriction endonucleases. this cell line was proved to be ...19979208425
molecular and biologic characterization of recombinant interferon-alpha2b.recombinant ifn-alpha2b (intron a, schering-plough corp, kenilworth, nj), derived from escherichia coli, is currently approved worldwide for the therapy of various cancers and chronic hepatitis b and c. we describe here the purity and identity tests for both physicochemical properties and bioactivity that have been developed for the characterization of highly purified ifn-alpha2b with a specific activity of 2.5 x 10(8) iu/mg protein. the data indicate that a product of high purity can be consist ...19979208872
rapid diagnosis of encephalomyocarditis virus infections in pigs using a reverse transcription-polymerase chain reaction.encephalomyocarditis virus (emcv) is widespread and the economic losses caused by an emcv outbreak in pig holdings and the similarity between a foot-and-mouth disease virus (fmdv) and an emcv infection in young piglets stress the need for a rapid, specific and broad diagnostic assay. an alternative to the time-consuming seroneutralisation assay, currently used for the characterisation of emcv, is described. an emcv specific reverse transcription-polymerase chain reaction (rt-pcr), using primers ...19979220393
serum creatine kinase-mb and lactate dehydrogenase-1 isoenzyme activities in piglets with encephalomyocarditis virus. 19979228695
development and characterization of a binary gene expression system based on bacteriophage t7 components in adenovirus vectors.to explore the utility of the bacteriophage t7 binary system in adenovirus (ad) vectors we constructed three ad5-based vectors containing the t7 rna polymerase (t7pol) gene in either early region 1 (e1) or e3. the recombinant ad vectors were either deficient (adt7pol1, adt7pol2) or competent (adt7pol3) for replication in human cells other than ad5 transformed (293) cells. to test the ability of the t7 polymerase produced by these vectors to drive gene expression, a reporter vector was constructe ...19979256069
comparative study of the pathogenic properties of a belgian and a greek encephalomyocarditis virus (emcv) isolate for sows in gestation.thirteen conventional sows were inoculated between 61 and 92 days of gestation with a belgium or a greek emcv isolate to investigate the difference in pathogenicity of both strains for sows in gestation. the belgian emcv strain was isolated from the offspring of a sow with productive failure and without myocardial lesions. the greek strain was isolated from a 3-month-old pig with prominent myocardial lesions. the present study demonstrates a transplacental virus transmission with fetal death fol ...19979270350
encephalomyocarditis virus infections in an australian zoo.fatal encephalomyocarditis virus (emcv) infections in a ring-tailed lemur (lemur catta), a squirrel monkey (saimiri sciureus), three mandrills (mandrillus sphinx), a chimpanzee (pan troglodytes), a pygmy hippopotamus (choeropsis liberiensis), and two goodfellows tree kangaroos (dendrolagus goodfellowi) occurred at taronga zoo. this is the first description of emcv in a zoological collection outside of the united states. regardless of species, the most common clinical presentation was sudden deat ...19979279403
coxsackieviruses and diabetes.insulin-dependent diabetes mellitus (iddm) is an autoimmune disease whose etiology is complex. both genetic susceptibility, which is polygenic, and environmental factors, including virus infections, appear to be involved in the development of iddm. in this review, we have tried to balance the discussion of diabetes by examining both immunological and virological perspectives. several mouse models, including viral and non-viral models, have been used to study diabetes. for this review, we include ...19979297970
protective role of interleukin-12 in viral myocarditis.the co-ordinate action of several cytokines determines the nature, severity and duration of myocarditis. interleukin (il)-12 mediates a broad range of effects on both innate and acquired immunity. however, the in vivo role of il-12 in viral myocarditis remains to be elucidated. to clarify the role of il-12 in viral myocarditis, we treated mice inoculated with the encephalomyocarditis virus (emcv), with recombinant il-12 and neutralizing anti-il-12 antibody. the successive administration of 10 ng ...19979299356
evaluation of the susceptibility of the 3c proteases of hepatitis a virus and poliovirus to degradation by the ubiquitin-mediated proteolytic system.the picornavirus 3c proteases are required for the processing of viral polyproteins during infections of host cells. here we report that the 3c protease of the hepatitis a virus, like that of the encephalomyocarditis virus, is a substrate for rapid, ubiquitin-mediated degradation in vitro. ubiquitin was shown to stimulate the turnover of the hepatitis virus 3c protease, and labeled protease was found to become incorporated into a mixture of high molecular weight species, which is characteristic ...19979299463
comparison of the pathogenic, antigenic and molecular characteristics of two encephalomyocarditis virus (emcv) isolates from belgium and greece.the pathogenicity of two porcine encephalomyocarditis virus (emcv) isolates for sows in gestation and young piglets was studied. one virus originated from a case of reproductive failure in pigs in belgium and the other from a case of acute myocarditis in pigs in greece. sows in the mid-gestation period and one- to two-month old piglets were inoculated with each isolate. the molecular relationship between both isolates was studied by determining the nucleotide sequence located across the junction ...19979300541
the alpha chemokine, interleukin 8, inhibits the antiviral action of interferon alpha.interferon (ifn) exhibits a potent antiviral activity in vitro and plays a major role in the early defense against viruses. like ifn, the proinflammatory chemokine, interleukin (il)-8, is induced by viruses and appears in circulation during viral infections. in an in vitro cytopathic effect assay for ifn, we found that il-8 can inhibit ifn-alpha activity in a dose-dependent manner. this action was reversed by specific monoclonal antibodies to il-8. the chemokine was able to attenuate the ifn-med ...19979314556
a new retroviral vector, ca1, to identify and select for cells expressing an inserted gene in vitro and in vivo.a new retroviral vector has been constructed that expresses genes encoding three different activities from a single transcript. this feature has been exploited to enable the efficient marking and selection of cells that express a gene of interest. the marker gene lacz, encoding beta-galactosidase, and neo, encoding neomycin phosphotransferase, for selection by the antibiotic g418, are expressed as a fusion, beta geo. the expression of beta geo is coordinated with expression of a gene of interest ...19979322757
mechanism of inactivation of enveloped viruses by the biosurfactant surfactin from bacillus subtilis.the antiviral activity of surfactin, a cyclic lipopeptide antibiotic and biosurfactant produced by bacillus subtilis, was determined for a broad spectrum of different viruses, semliki forest virus (sfv), herpes simplex virus (hsv-1, hsv-2), suid herpes virus (shv-1), vesicular stomatitis virus (vsv), simian immunodeficiency virus (siv), feline calicivirus (fcv), murine encephalomyocarditis virus (emcv). in vitro experiments showed biphasic virus inactivation kinetics for enveloped viruses during ...19979324997
factors influencing induction and reversal of virus induced diabetes.injection of encephalomyocarditis virus -d strain in sjl/j mice leads to development of diabetes. in order to ascertain various factors involved in this process, effect of age of the host, dose of virus and glucose pretreatment on incidence of diabetes and its possible reversal were studied. blood and urine glucose levels of control and experimental mice were followed for 6-8 weeks to reveal diabetic and reversal from diabetic state. it is observed that incidence of diabetes is directly proporti ...19979332172
improved ebv-based shuttle vector system: dicistronic mrna couples the synthesis of the epstein-barr nuclear antigen-1 protein to neomycin resistance.use of ebv-based vector systems has been limited by the requirement to generate ebna+ cells which are 'permissive' for replication of an orip-vector. in current constructs, selectable marker and ebna-1 are not always co-expressed. this is a significant problem since the ebna-1 gene product can be toxic in some cell types and may be selected against. in this paper, we describe a gene construct that overcomes this limitation. we have exploited the piconaviral internal ribosome entry site to allow ...19979332352
comparison of various expression plasmids for the induction of immune response by dna immunization.intramuscular injection of plasmid dna is an efficient method to introduce a foreign gene into a live animal. we investigated several factors affecting the gene transfer efficiency and the following immune response by intramuscular injection of plasmid dna. when the strength of several highly efficient viral promoters was compared in muscle by using the chloramphenicol acetyltransferase (cat) gene as an indicator, cytomegalovirus (cmv) immediate early promoter was found to be stronger than any o ...19979339893
dicistronic tagging of genes active in embryonic stem cells of mice.a gene-trap vector, pwh14, has been developed to tag genes expressed in embryonic stem (es) cells of the mouse. the approach relies on the ability of the endogenous promoter to drive promoterless neo-ires-lacz construct producing a dicistronic mrna consisting of the neomycin-resistance (neo) gene and the beta-galactosidase gene sequence. the neo gene produces a chimeric protein with the truncated product of the tagged gene and serves as a selectable marker for an insertion into an expressed gene ...19979339894
tetracycline-mediated suppression of gene expression with a new dicistronic retroviral vector.since the first description of the helper-free retrovirus vector by mann et al. (1983), many improvements have been introduced to the system to increase titer, or to achieve better expression of the transduced genes in cells of different lineage. the typical form of recombinant retrovirus vector utilizes its 5' long terminal repeat (ltr) as a promoter unit for the transcription of the inserted gene(s), which allows only the constitutive expression of the inserted gene(s) in target cells. althoug ...19979339896
adenovirus infection inactivates the translational inhibitors 4e-bp1 and 4e-bp2.infection with many viruses results in the selective shutoff of host protein synthesis. a common target for virus interference with host protein synthesis is the cap-binding protein complex, eif4f. the large subunit of the complex, eif4g, is cleaved upon picornavirus (except cardiovirus) infection. infection with adenovirus and influenza virus causes dephosphorylation of the cap-binding subunit, eif4e. recently, it has been shown that infection with poliovirus or encephalomyocarditis virus activ ...19979344920
interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate-dependent rnase l.2',5'-oligoadenylate-dependent rnase l functions in the interferon-inducible, rna decay pathway known as the 2-5a system. to determine the physiological roles of the 2-5a system, mice were generated with a targeted disruption of the rnase l gene. the antiviral effect of interferon alpha was impaired in rnase l-/- mice providing the first evidence that the 2-5a system functions as an antiviral pathway in animals. in addition, remarkably enlarged thymuses in the rnase l-/- mice resulted from a sup ...19979351818
efficient long-term coexpression of a hammerhead ribozyme targeted to the u5 region of hiv-1 ltr by linkage to the multidrug-resistance gene.ribozymes as anti-hiv-1 agents hold promise for the treatment of aids. they can be delivered into cells either exogenously or through an expression system. for effective protection against hiv-1, sufficient and sustained amounts of the antiviral ribozymes must be delivered into target cells. the coexpression of a dominant selectable marker with ribozymes would serve to enrich for cells containing the molecular antiviral and facilitate prolonged expression of these ribozymes. the multidrug resist ...19979361910
pharmacological biocompatibility between intravesical preparations of bcg and interferon-alpha 2b.to determine if bcg and interferon alpha-2b are mutually compatible as mixed intravesical agents for clinical bladder cancer therapy.19979366382
gain or loss of diabetogenicity resulting from a single point mutation in recombinant encephalomyocarditis virus.molecular pathogenic mechanisms for virus-induced disease have received considerable attention. encephalomyocarditis (emc) virus-induced diabetes in mice has been extensively studied to elucidate the cellular and molecular mechanisms involved in the development of this disease. in this study, we report for the first time that a single point mutation at nucleotide position 3155 or 3156 of the recombinant emc viral genome, located on the major capsid protein vp1, which causes an amino acid change, ...19979371645
a novel dicistronic aav vector using a short ires segment derived from hepatitis c virus genome.adeno-associated virus (aav) vectors have a limited capacity for packaging dna. to insert both a therapeutic gene and a selectable marker gene in the same aav vector efficiently, we developed a novel dicistronic aav vector containing a 230 base pairs (bp) internal ribosome entry site (ires) element derived from hepatitis c virus (hcv) genome and a 420 bp blasticidin s-resistance gene (bsr) as a small selectable marker in the second cistron. the 650 bp hcv ires-bsr construct was placed downstream ...19979373150
dicistronic lacz and alkaline phosphatase reporter constructs permit simultaneous histological analysis of expression from multiple transgenes.we report here the development of convenient dicistronic transgenic markers for the rapid and efficient simultaneous analysis of transgene activity in transgenic mice. two sensitive histological markers, the beta-galactosidase (beta-gal)-encoding lacz gene and the human placental alkaline phosphatase (hpap) gene, have been fused to the internal ribosome entry sequence (ires) from the encephalomyocarditis virus, which directs efficient mrna cap-independent entry of the translation apparatus in ma ...19979383553
expression of a recombinant monoclonal antibody from a bicistronic mrna.the variable regions of the murine monoclonal antibody a1, which effectively neutralizes the infection of susceptible cells by the murine hepatitis virus strain jhm, were cloned, sequenced, and expressed in mammalian cells as a functional recombinant antibody. to accomplish the concurrent synthesis of both antibody chains, the light- and heavy-chain-coding regions were inserted into a bicistronic expression cassette based on the encephalomyocarditis virus internal ribosomal entry site. the strat ...19979388025
retroviral transfer of herpes simplex virus-thymidine kinase and beta-galactosidase genes into u937 cells with bicistronic vector.in this study we describe a new retroviral vector utilizing an internal ribosome entry site (ires) from encephalomyocarditis virus to co-express two genes. one is the herpes simplex virus type 1 thymidine kinase gene (hsv-tk) which induces sensitivity to ganciclovir, and the second is the bacterial beta-galactosidase gene (lacz) which was revealed by an histochemical staining with 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside (x-gal). we engineered the u937 human cell line to co-express bo ...19979403006
effects of levamisole, an immunomodulator, upon murine encephalomyocarditis virus myocarditis.to test the therapeutic efficacy of levamisole, 5-week-old dba/2 mice were inoculated intraperitoneally with 10 plaque-forming units of encephalo-myocarditis virus. levamisole (2.5 mg/kg/per day) was administered intraperitoneally daily, starting simultaneously with the virus inoculation, in experiment i for 14 days, and daily on days 14 to 28 in experiment ii in mice that survived to 14 days after virus inoculation. in experiment i, survival was higher, the severity of myocarditis was less, and ...19979403310
[serologic studies of domestic cats for potential human pathogenic virus infections from wild rodents].for several viral infections a reservoir in wild rodents has been demonstrated. some of the agents are known or suspected to be pathogenic for humans. because improvements in hygiene have reduced direct human contact with rodents, domestic cats could be acting as active transmitters of these viruses from rodents to man. we selected 4 such pathogens--ortho- and parapox-, hanta- and encephalomyocarditis viruses--which, in different ways, may lead to serious human illness: ortho- and parapoxvirus i ...19969409901
protective immunity against heterologous challenge with encephalomyocarditis virus by vp1 dna vaccination: effect of coinjection with a granulocyte-macrophage colony stimulating factor gene.for dna vaccination studies, recombinant vp1 protein of encephalomyocarditis virus (emcv) was produced from escherichia coli, and eukaryotic vp1 expression vector, pct-gs-vp1, was generated and used as a dna vaccine. mice were immunized intramuscularly (i.m.) with pct-gs-vp1 in the presence or absence of plasmid dna expressing granulocyte-macrophage colony stimulating factor (gm-csf), and were subsequently analyzed for their anti-vp1 immune responses with recombinant vp1 in elisa. immunization o ...19979413089
isolation of a measles virus variant: protection of newborn mice from measles encephalitis by 24 h prior intracerebral inoculation with the variant.a small plaque mutant with reduced neurovirulence in newborn mice was obtained from edmonston strain measles virus after propagation for 5 months in nih3t3 cells. it retained the antigenicity of the parental virus and tended to induce higher neutralizing antibody titers in the adult balb/c mice. the intracerebral (but not intraperitoneal) inoculation of the live mutant virus one day before prevented the newborn balb/c mice from encephalitis caused by the intracerebral challenge with the parental ...19979413503
the internal ribosomal entry site of the encephalomyocarditis virus enables reliable coexpression of two transgenes in human primary t lymphocytes.it is essential for the improvement of adoptive cell therapies to generate efficiently large populations of human primary t cells that reliably express a suicide gene conferring drug sensitivity, such as herpes simplex virus thymidine kinase (hsvtk). we show here that an optimized dicistronic vector containing the encephalomyocarditis virus (emcv) internal ribosomal entry site (ires) is functional in human primary. t lymphocytes that bear on average one integrated vector copy per cell. we demons ...19979415319
total number and size distribution of motor neurons in the spinal cord of normal and emc-virus infected mice--a stereological study.the encephalomyocarditis virus of the diabetogenic m-strain (emc-m) is known to cause diabetes in mice. the emc-m virus has also been shown to cause paresis in some of the infected animals. the clinical features include an acute ascending predominantly motor paralysis, developing within days. this resembles acute idiopathic polyneuritis. the alpha motor neurons would be a possible target for the virus, so two parameters, the total number and the size distribution of motor neurons, were therefore ...19979418991
high-level expression of exogenous genes by replication-competent retrovirus vectors with an internal ribosomal entry site.we report the construction of two types of rous sarcoma virus (rsv)-based replication-competent avian retrovirus vectors, ir1 and ir2 to express an exogenous gene at a very high level. in these vectors, the internal ribosomal entry site (ires) derived from encephalomyocarditis virus (emcv) was inserted between the env gene and an exogenous gene. the ir1 vector retains the splicing acceptor site that is present in the downstream of the env gene while the ir2 vector lacks it. using a v-fos mutant ...19979427541
resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein.the interferon (ifn)-induced promyelocytic leukemia (pml) protein is specifically associated with nuclear bodies (nbs) whose functions are yet unknown. two of the nb-associated proteins, pml and sp100, are induced by ifn. here we show that overexpression of pml and not sp100 induces resistance to infections by vesicular stomatitis virus (vsv) (a rhabdovirus) and influenza a virus (an orthomyxovirus) but not by encephalomyocarditis virus (a picornavirus). inhibition of viral multiplication was de ...19989444998
the polyoma virus t antigen interferes with interferon-inducible gene expression.murine polyoma virus (mpyv) is a small dna virus that induces tumors in multiple tissues of infected host. in this investigation, we show that cell lines derived from wild type virus-induced breast tumors are resistant to the growth inhibitory action of interferon beta (ifn-beta). furthermore, replication of heterologous viruses such as vesicular stomatitis virus and encephalomyocarditis virus was not inhibited by ifn-beta in these cells. this effect was due to inhibition of ifn-stimulated gene ...19989448289
the use of cytokine inhibitors. a new therapeutic insight into heart failure.cytokines are being increasingly recognized as important factors in the pathogenesis and pathophysiology of heart failure. elevated levels of circulating cytokines have been reported in patients with heart failure, and various cytokines have been shown to depress myocardial contractility in vitro and in vivo. we have recently compared the effects on cytokine production of drugs for therapy of heart failure that have different effects on survival. amrinone, pimobendan and vesnarinone, phosphodies ...19979464576
antibodies against emc virus rna-vpg recognize tyr-(5'p-->o)-pu and immunostain infected cells.covalent complexes of nucleic acids and proteins are widespread among viruses. covalent complexes of rna and proteins are proposed to exist in eukaryotic cells. the goal of this work was to obtain specific antibodies to the covalent linkage unit (clu) between virus rna and protein to search cellular rna-protein complexes. antibodies were generated by direct immunization of a rabbit with the bsa-coupled emc virus rna-vpg complex. by a dot-blot immunoassay and immunofluorescent microscopy it was f ...19989475169
calcium channel blocker-induced protection against cardiovascular damage.the therapeutic effects of calcium channel blockers on heart failure are controversial. however, a recent clinical trial demonstrated a favorable effect of amlodipine on survival rates in patients with heart failure resulting from nonischemic dilated cardiomyopathy. there are a number of studies showing that cytokines generated by activated immune cells cause an increase in nitric oxide (no) via induction of no synthase (nos), which results in a direct negative inotropic effect and a modulation ...19979488194
interferon has no protective effect during acute or persistent reovirus infection of mouse sc1 fibroblasts.mouse sc1 fibroblasts can support reovirus multiplication although they exhibit a partial resistance to viral-induced cytopathology; a significant percentage of infected sc1 cells can remain viable while becoming persistently infected by the virus. in the present study, the possible role of interferon on the fate of reovirus-infected cells was investigated. treatment of mouse l fibroblasts with beta-interferon resulted in a reduced viral efficiency of plating while essentially no effect was obse ...19979498612
co-expression of human adenosine deaminase and multidrug resistance using a bicistronic retroviral vector.current gene therapy protocols designed to treat adenosine deaminase (ada) deficiency and other metabolic disorders suffer from low-efficiency delivery to target cells and a lack of long-term stability in expression of the therapeutic proteins. these problems may be resolved by use of an in vivo dominant selection. the multidrug transporter (mdr1) has been suggested as a useful selective marker for gene therapy. in this work, we co-expressed ada and mdr1 cdna in a retroviral vector using an inte ...19989508046
protective effects of mu-fang-ji-tang against myocardial injury in a murine model of congestive heart failure induced by viral myocarditis.the effects of mu-fang-ji-tang (tj-36), a traditional chinese herbal medicine, were studied in a murine model of congestive heart failure induced by viral myocarditis. in the group of animals treated with mu-fang-ji-tang in a dose of 1.5g/kg/day, the heart weight to body weight ratio was significantly lower than in the control group (p<0.01). histopathological grades were also significantly lower in the mu-fang-ji-tang treated group than in the placebo group (p<0.05). furthermore, survival was i ...19989519794
rnase l mediates the antiviral effect of interferon through a selective reduction in viral rna during encephalomyocarditis virus infection.the 2',5'-oligoadenylate (2-5a) system is an rna degradation pathway which plays an important role in the antipicornavirus effects of interferon (ifn). rnase l, the terminal component of the 2-5a system, is thought to mediate this antiviral activity through the degradation of viral rna; however, the capacity of rnase l to selectively target viral rna has not been carefully examined in intact cells. therefore, the mechanism of rnase l-mediated antiviral activity was investigated following encepha ...19989525594
effects of intranasal administration of recombinant murine interferon-gamma on murine acute myocarditis caused by encephalomyocarditis virus.viral myocarditis has been strongly implicated in the pathogenesis of dilated cardiomyopathy as well as acute myocarditis. among the antiviral therapies, interferons (ifns) have been widely studied and become very important in clinical practice.19989529271
combination of ok432 and human interferon-alpha for treating viral-induced diabetes mellitus in mice.we investigated the therapeutic effects of ok432 (picibanil; cas39325-1-4), an immunomodulator that is derived from the su strain of streptococcus pyogenes. this agent was administered alone or combined with human interferon-alpha in a murine model of insulin-dependent diabetes mellitus. interferon-alpha inhibits viral replication, reducing the incidence of virus-induced iddm. groups of dba/2 mice (n = 25 per group) received an intraperitoneal injection of ok432 and interferon-alpha daily for 16 ...19989548400
evolution of a common structural core in the internal ribosome entry sites of picornavirus.the translational control involving internal ribosome binding occurs in poliovirus (pv), human rhinoviruses (hrv), encephalomyocarditis virus (emcv), foot-and-mouth disease virus (fmdv), and hepatitis a virus (hav). internal ribosome binding utilizes cis-acting genetic elements of approximately 450 nucleotides (nt) termed the internal ribosome entry sites (ires) found in these picornaviral 5'-untranslated region (5'utr). although these ires elements are quite different in their primary sequence, ...19989562889
determination of encephalomyocarditis viral diabetogenicity by a putative binding site of the viral capsid protein.the molecular mechanism by which some, but not all, variants of encephalomyocarditis (emc) virus selectively infect pancreatic beta-cells in mice and induce iddm has been an enigma for more than a decade. we report here that the binding site of the emc viral capsid protein vp1 determines viral diabetogenicity. recombinant chimeric emc viruses containing threonine, serine, proline, aspartic acid, or valine at position 152 of the major capsid protein vp1 bind poorly to beta-cells. in contrast, rec ...19989568690
type i interferons are essential mediators of apoptotic death in virally infected cells.the interferons (ifns) have been extensively studied in the context of host defence against viral infection. in the established model of ifn action, virally infected cells secrete type i ifns (ifn-alpha/beta) which induce an antiviral state in uninfected cells. however, it is not clear how ifns function on the infected cells. it has been reported that cells infected by some viruses die by apoptosis.19989581980
structural and functional differences between glycosylated and non-glycosylated forms of human interferon-beta (ifn-beta).two recombinant ifn-beta products have been approved for the treatment of multiple sclerosis, a glycosylated form with the predicted natural amino acid sequence (ifn-beta-1a) and a non-glycosylated form that has a met-1 deletion and a cys-17 to ser mutation (ifn-beta-1b). the structural basis for activity differences between ifn-beta-1a and ifn-beta-1b, is determined.19989587963
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