Publications

interferon-gamma is cytotoxic for normal mouse fibroblasts: enhancement by tumor necrosis factor and interleukin 1.	tumor necrosis factor (tnf) and interleukin-1 (il-1) are cytotoxic for certain tumor cells but have a proliferative effect on normal cells. here we show that interferon-gamma (ifn-gamma) can be cytotoxic for normal cells, in particular mouse embryonic fibroblasts. the cytotoxicity effect is observed with immuno-purified recombinant mouse ifn-gamma (muifn-gamma) at concentrations of 1,000 i.u./ml and can be neutralized by anti-muifn-gamma monoclonal antibodies. the effect appears 48 h after initi ...	1989	2497277
2'-5'-oligoadenylate synthetase gene expression in normal and murine sarcoma virus-transformed nih 3t3 cells.	mouse fibroblasts transformed by murine sarcoma virus (msv) are highly sensitive to the antiproliferative effect of interferon (ifn) (m. bakhanashvili, d. h. wreschner, and s. salzberg, cancer res. 43:1289-1294, 1983). to elucidate the mechanism leading to this ifn sensitivity, the expression of the 2'-5'-oligoadenylate synthetase (2-5a synthetase) gene, the presence of the 2-5a synthetase protein, and the level of its enzymatic activity were determined in ifn-treated and untreated cultures. nih ...	1989	2536824
mengo virus maturation is accompanied by c-terminal modification of capsid protein vp1.	we have demonstrated that the c-terminal ends of the vp1 proteins of mengo virus undergo a postassembly trimming of three amino acid residues. a variable proportion of the vp1 molecules isolated from purified virions terminate at glu 277, which corresponds to the initial viral protease 3c cleavage site. the remainder of the vp1 molecules terminates at leu 274. when chymotrypsin treatment is included in the virus purification procedure, leu 274 is the exclusive c-terminal amino acid of the vp1 mo ...	1989	2536988
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- ...	1989	2538661
[use of direct calorimetry for continuously following the course of experimental infections in the mouse].	to obtain information about early symptoms of infection measurements of heat production were performed in experimentally infected animals. as a model mengo virus-infected mice were used. construction and physical properties of the flow calorimeter device are described. fever was not detected by method used. however, deviations from normal behaviour of the animals were demonstrated as a result of the relationship between motoric activity and heat produced. furthermore, the method may be particula ...	1989	2551106
structure determination of mengo virus.	the structure of mengo virus was determined to 3.0 a resolution using human rhinovirus 14 as an initial phasing model at 8.0 a resolution. oscillation diffraction photographs were collected at the cornell high energy synchrotron source using orthorhombic mengo virus crystals. the crystal space group was p2(1)2(1)2(1), a = 441.4, b = 427.3 and c = 421.9 a, with one icosahedral particle per asymmetric unit, giving 60-fold noncrystallographic redundancy. the orientations of the four viral particles ...	1989	2559754
[transmission cycles of arboviruses in madagascar].	some arboviruses are highly pathogenic for men or animals. arboviruses epidemiological patterns in madagascar were determined by entomological, serological, and virological surveys. we listed potentials arboviruses vectors in madagascar. entomological results generated by us during five years, as well as prior to, are shown. we caught more than 150,000 hematophagous arthropods, belonging to 107 species at least. 3 of these species were new. 4183 inoculation pools were done. we studied serollogic ...	1989	2576622
[arbovirus transmission cycles in madagascar].	some arboviruses are highly pathogenic for men or animals, arboviruses epidemiological patterns in madagascar were determined by entomological, serological, and virological surveys. we listed potentials arboviruses vectors in madagascar. entomological results generated by us during five years, as well as prior to, are shown. we caught more than 150,000 hematophagous arthropods, belonging to 107 species at least. 3 of these species were new. 4183 inoculation pools were done. we studied serologica ...	1989	2751393
functional aspects of the capsid structure of mengo virus.	the three-dimensional structure of the mengo virus capsid has been determined at a resolution of 3.0 a. this achievement is discussed in an historical context, and the general features of picornavirus capsid design are presented. the dynamic functional aspects of the mengo virus capsid--namely its ability to interact with specific receptors on host cells, to dissociate and release the viral genomic rna into the cellular cytoplasm, to assemble with progeny rna molecules and form new virions, and ...	1990	1965133
the role of viruses and environmental factors in the induction of diabetes.	the development of iddm results from the destruction of pancreatic beta cells. genetic factors, various immune system alterations, and environmental factors have been studied as the possible causes of iddm. the concordance rate for developing iddm between monozygotic twins approaches 50%, suggesting that genetic factors are necessary, but nongenetic factors such as various immune system alterations and environmental factors also influence the clinical expression of genetic susceptibility. enviro ...	1990	2073786
attenuation of mengo virus through genetic engineering of the 5' noncoding poly(c) tract.	the murine cardioviruses, such as the mengo and encephalomyocarditis viruses, and the bovine aphthoviruses, such as foot-and-mouth disease virus, are distinguished among positive-strand rna viruses by the presence of long homopolymeric poly(c) tracts within their 5' noncoding sequences. although the specific lengths (60-350 bases) and sequence discontinuities (for example, uridine residues) that sometimes disrupt the homopolymer have served to characterize natural viral isolates, the biological ...	1990	2153940
relief of cytotoxicity and enhancement of interferon inducer activity of double-stranded rna by eukaryotic initiation factor 2.	double-stranded rna (dsrna) is a powerful interferon inducer but also possesses toxic properties. dsrna was shown previously to inhibit translation by causing the inactivation of eukaryotic initiation factor 2 (eif-2) and to bind tightly to this protein. the cytotoxicity of dsrna was analyzed simultaneously with the induction of interferon in murine fibroblast cultures. incubation of dsrna with eif-2 leads to a significant reduction in toxicity, concomitant with a marked stimulation of interfero ...	1990	2154884
conformational variability of a picornavirus capsid: ph-dependent structural changes of mengo virus related to its host receptor attachment site and disassembly.	the structure of mengo virus had been determined from crystals grown in the presence of 100 mm phosphate buffer at ph 7.4. it is shown that mengo virus is poorly infectious at the phosphate concentration similar to that in which it was crystallized. maximal infectivity is achieved at 10 mm phosphate or less in physiological saline. the phosphate effect is ameliorated when the ph is lowered to 4.6. although it has not been possible to study the crystal structure of the virus at low phosphate conc ...	1990	2155508
structural refinement and analysis of mengo virus.	the structure of mengo encephalomyelitis virus was refined at 3 a resolution with a final r-factor of 0.221 and a root-mean-square deviation from idealized bond lengths of 0.019 a for 10 a to 3 a data with f greater than or equal to 3 sigma(f). the hendrickson-konnert refinement was restrained by the phases derived from the molecular replacement averaging procedure and constrained by the icosahedral symmetry of the virus. the virus consists of 60 protomers each having three major subunits, vp1, ...	1990	2156078
the inhibition of mouse l-cell 45 s ribosomal rna processing is a highly uv-resistant property of vesicular stomatitis virus.	in mouse l cells infected with vesicular stomatitis virus (vsv), the synthesis of 45 s rrna and its conversion to 28 s and 18 s rrna are inhibited during the course of infection. evidence is presented that the lack of accumulation of stable rrna species results not only from the decreased transcription and processing of 45 s rrna, but also from an increased breakdown of pre-rrna or stable rrna during processing. in cells prelabeled with [3h]uridine and then infected, the 28 s and 18 s rrna speci ...	1990	2162117
the alpha subunit of eucaryotic initiation factor 2 is phosphorylated in mengovirus-infected mouse l cells.	infection of mouse l cells with mengovirus resulted in the activation of a protein kinase (pk) that selectively phosphorylated the small, 38,000-molecular-weight alpha subunit of eucaryotic initiation factor 2 (eif-2) in vitro. the mengovirus-activated kinase was detected in vitro approximately 3 h after virus adsorption. the ratio of phosphorylated to unphosphorylated eif-2 also increased in vivo between 3 and 7 h after adsorption. the virus-activated kinase fractionated with the ribosomal pell ...	1990	2166823
ph 2 instability of a mutant of mengovirus is related to its interferon sensitivity.	the is-1 mutant of mengovirus is 100 times more sensitive to interferon (ifn) than wild type, as measured by a yield reduction assay in the g3 line of mouse l cells, and is also much more readily inactivated at ph 2. neither isolated nor encapsidated rna is degraded under these conditions, which suggests that the ph-sensitive region resides on the virus coat. one-third of the viruses selected for resistance to low ph also showed enhanced resistance to ifn. attempts to isolate ifn resistant strai ...	1990	2172408
effects of the copper chelators diethyldithiocarbamate and bathocuproine sulfonate on interferon and its antiviral state.	treatment of mouse l cells with two structurally unrelated chelators of copper ions, diethyldithiocarbamate (ddc) or bathocuproine sulfonate (bcs), completely inhibited the ability of interferon (ifn) to inhibit mengovirus growth. however, mengovirus virions were inactivated by incubation with ddc, and ddc induced a generalized inhibition of cellular rna and protein synthesis, possibly combined with the inactivation of one or more specific enzymatic activities involved in the establishment or ma ...	1990	1691765
2',5'-oligoadenylate synthetase gene expression in revertants of ras-transformed nih3t3 fibroblasts.	persistent revertant (pr) cells of ha-ras-transformed nih3t3 fibroblasts, isolated after prolonged treatment with interferon (ifn), have been previously described. pr cells remain nontumorigenic even after ifn withdrawal. to investigate the mechanisms responsible for the stable phenotypic reversion, we have now examined the potential involvement of an endogenous ifn and the 2',5'-oligoadenylate (2-5a) synthetase pathway. northern blot analysis revealed an increased level of 2-5a synthetase trans ...	1990	1699771
characterization of mengo virus neutralization epitopes.	a set of four monoclonal antibodies which neutralized the infectivity of mengo virus was used to select 20 non-neutralizable (escape) mutants. altered amino acids were identified by sequence analyses of the capsid-coding regions of the mutant virus genomes. mutations were found predominantly in proteins vp2 and vp3, while mutations in vp1 were detected only as second mutations. the mengo virus vp2 mutations at amino acid residues 2144, 2145, 2147, and 2148 align with site nlm ii in human rhinovi ...	1991	1704653
neutralizing antibody to mengo virus, induced by synthetic peptides.	a peptide from the carboxyl-terminal region of the mengo virus capsid protein vp1, representing residues 259 to 277, can induce serum neutralizing (sn) antibodies in both the mouse and guinea-pig. this peptide, termed f164, also induces high levels of protective neutralizing antibodies in mice subsequent to immunization; 87 to 100% of mice are refractory to the effects of an intraperitoneal challenge of 100 ld50 of mengo virus. the mouse model discussed herein will prove useful for studying the ...	1991	1709682
catalysis of poliovirus vp0 maturation cleavage is not mediated by serine 10 of vp2.	the maturation of the poliovirus capsid occurs as the result of a single unexplained proteolytic event during which 58 to 59 copies of the 60 vp0 capsid protein precursors are cleaved. an autocatalytic mechanism for cleavage of vp0 to vp4 and vp2 was proposed by arnold et al. (e. arnold, m. luo, g. vriend, m. g. rossman, a. c. palmenberg, g. d. parks, m. j. nicklin, and e. wimmer, proc. natl. acad. sci. usa 84:21-25, 1987) in which serine 10 of vp2 is activated by virion rna to catalyze vp4-vp2 ...	1991	1845893
mutational analysis of regulation of mhc and anti-viral genes.	ctl-mediated selection for loss of expression of mta by h-2-heterozygous sv40-transformed mouse fibroblasts (line 24sv) produced an unusual phenotypic class of maternally transmitted ag negative mutants defective in both mhc expression and in anti-viral activity. severely reduced surface expression of class i mhc ag from multiple loci of both haplotypes correlated with low levels of mhc h chain and beta 2-microglobulin mrna. inasmuch as ifn can up-regulate class i expression and some fibroblasts ...	1991	1848575
cell microfilaments disorganization is an early cytopathic effect in mengo virus replication.	the effect of mengo virus replication on cell morphology and cytoskeletal organization has been studied in lw murine fibroblasts. cell modifications were followed by scanning electron microscopy. the cytoskeleton was stained by immunofluorescence using antitubulin antibodies for microtubules, antivimentin antibodies for intermediate filaments and rhodamine-conjugated phalloidin for microfilaments. cytopathic effects began in the early phase of virus infection amd were correlated with broad modif ...	1991	1649961
sequence and structural elements that contribute to efficient encephalomyocarditis virus rna translation.	the nucleotide sequence of the 5' nontranslated region of encephalomyocarditis virus (emcv-rueckert) was determined, and a consensus rna structural model for this sequence (850 bases) and three other poly(c)-containing cardioviruses (mengovirus, emcv-b, and emcv-d) was created through reiterative use of a minimum-free-energy folding algorithm. the rna elements within this region which contribute to translation of emcv proteins were mapped in cell-free reactions programmed with cdna-derived rna t ...	1992	1310768
three-dimensional structure of theiler murine encephalomyelitis virus (bean strain).	depending on the strain, theiler murine encephalomyelitis virus (tmev) may cause acute encephalitis or chronic demyelinating disease, which is associated with viral persistence in mice. persistent central nervous system infection and demyelination by the less-virulent tmev has provided a useful animal model for the human demyelinating disease multiple sclerosis. the less-virulent bean strain of tmev was crystallized and its atomic structure was determined by x-ray crystallography. the alpha-carb ...	1992	1312722
proteolytic processing of the cardioviral p2 region: primary 2a/2b cleavage in clone-derived precursors.	the primary 2a/2b cleavage within cardiovirus polyprotein was examined by construction of cdna plasmids which linked fragments from the p2 region of encephalomyocarditis virus (emcv) and mengovirus genomes to the emcv 5' nontranslated region. when rna transcripts from these clones were tested in reticulocyte extracts, the synthesized proteins were cotranslationally processed at the 2a/2b site. no viral segments outside of the p2 region were required for this activity. engineered deletions which ...	1992	1325705
molecular and structural basis of hemagglutination in mengovirus.	the molecular and structural basis of mengovirus hemagglutination (ha) was investigated by the comparison of nucleotide sequences of the entire capsid coding regions of an ha+ variant, two ha- mutants, 205 and 280, and two ha+ revertants of 205. the mutants were selected after acridine mutagenesis of mengovirus-37a, a heat-stable and ha+ variant that is neurotropic in mice. ha+ revertants of mutant 205 were isolated from brain tissue of mice inoculated with mutant 205. the nucleotide sequences w ...	1992	1326807
virus-specific effects of recombinant porcine interferon-gamma and the induction of mx proteins in pig cells.	interferon-alpha (ifn-alpha) and -gamma differed in their action against influenza virus and vesicular stomatitis virus (vsv) on pig cells. recombinant ifn-alpha severely impaired the cytopathic effect of vsv on pk-15 cells, whereas recombinant porcine ifn-gamma did not. ifn-alpha impaired also the replication of vsv and of influenza virus in primary pig kidney cells in contrast to ifn-gamma, which failed to induce an efficient antiviral state against both viruses. otherwise, the ifn system seem ...	1992	1337754
dissociable antiviral activities directed against cardioviruses are expressed in l cells treated with interferon.	interferon (ifn) restricts a wide variety of viruses. to do so it elicits many antiviral pathways. for example, subclones of the same cell line with a reduced antiviral spectrum are thought to lack one or more antiviral pathways. our line of l cells exhibits two distinct antiviral activities. the first delays the yield of both wild-type mengovirus (is+) and an ifn-sensitive mutant (is-1). the second specifically inhibits is-1 virus yields 100-fold. from these cells, a subclone was isolated which ...	1992	1383407
ion channels in icosahedral virus: a comparative analysis of the structures and binding sites at their fivefold axes.	an analysis of the crystallographically determined structures of the icosahedral protein coats of tomato bushy stunt virus, southern bean mosaic virus, satellite tobacco necrosis virus, human rhinovirus 14 and mengovirus around their fivefold axes is presented. accessibilities surfaces, electrostatic energy profile calculations, ion-protein interaction energy calculations, free energy perturbation methods and comparisons with structures of chelating agents are used in this study. it is concluded ...	1992	1384743
comparison of surface properties of picornaviruses: strategies for hiding the receptor site from immune surveillance.	the surface topology and sequence conservation of different picornaviruses have been compared using molecular graphics and statistical analyses. the comparisons suggest that the canyons, surface depressions encircling the fivefold axes, are the sites of receptor attachment of enteroviruses as well as human rhinovirus (hrv). in hrv14, the receptor binding footprint extends beyond the canyon (olson et al. (1993), proc. natl. acad. sci. usa 90, 507-511), but these more exposed regions are not conse ...	1993	8337843
molecular identification of cardioviruses by enzymatic amplification.	cardiovirus specific sequences located in the 5' ntr are used to amplify viral rna by pcr. general primers were selected for the amplification of cardioviruses, including encephalomyocarditis virus (emcv), mengovirus and theiler's murine encephalomyelitis virus (tmev. additionally, echo virus type 22, an atypical enterovirus, could also be detected with the general cardiovirus primers. an internal encephalomyocarditis virus specific probe and a general cardiovirus probe are used to discriminate ...	1993	7511789
the virion of mengovirus contains anti-interferon activity.	many viruses are resistant to the antiviral state induced by interferon (ifn) in certain cell lines because they produce factors having anti-ifn activity (aia). we show here that is+, a mengovirus strain resistant to low concentrations of ifn, also produces an aia, but that an ifn-sensitive mutant (is-1) does not. this activity was detected when is+ rescued is-1 from the antiviral state induced in mouse l cells by mouse ifn. the mengovirus aia was found in cell lysates prepared from cells infect ...	1993	7681091
does physiological interferon play a role in mengo virus infection of mice?	nzb, balb/c and c3h mice, differing in their production of physiological interferon (ifn), were used as models to investigate its role in their resistance to mengo virus infection. these mouse strains also differ in their susceptibility to the infection. nzb and balb/c mice, producing higher titers of physiological ifn than c3h mice, proved to be less resistant to the infection than the latter mouse strain. this suggests that physiological ifn does not play protective role against mengo virus in ...	1993	7692712
identification of mengo virus t helper cell epitopes.	to identify mengo virus-specific t cell epitopes in mice (the natural host for the virus), lymph node cells were obtained from balb/c (h-2d) mice, previously immunized with u.v.-inactivated virus, and stimulated in vitro with each of 116 overlapping peptides (10 to 18 residues long) covering the entire capsid coding region (834 amino acids). t cell epitopes were defined on the basis of specific peptide-induced lymphocyte proliferation. where proliferation occurred, immunological characterization ...	1994	7525861
attenuated mengo virus as a vector for immunogenic human immunodeficiency virus type 1 glycoprotein 120.	introduction of a sequence encoding 147 amino acids from human immunodeficiency virus type i (hiv-1) strain mn glycoprotein gp120 into the rna genome of the stably attenuated mengo virus strain vm16 yielded an infectious recombinant virus, vmln450, which expressed the heterologous hiv-1 sequence along with the normal mengo virus proteins. the hiv-1 gp120 sequence, fused to the amino terminus of the short, nonstructural mengo virus leader polypeptide was recognized by a gp120 v3 loop-specific mon ...	1994	7937890
a search for candidate viruses in type 1 diabetic pancreas using the polymerase chain reaction.	in order to investigate a possible viral aetiology for type 1 diabetes the polymerase chain reaction (pcr) technique was used. pancreatic tissue from type 1 diabetic subjects was examined for the presence of a panel of common viruses. primers specific for mumps, measles, cytomegalovirus, and epstein barr virus, as well as primers located in a highly conserved region of the enterovirus genome which are capable of detecting all of the following family members: coxsackie b, echovirus, polio, mengov ...	1994	7955973
purification and characterization of the u-particle, a cellular constituent whose synthesis is stimulated by mengovirus infection.	we have isolated a cellular protein particle whose synthesis is induced by infection with mengovirus or tmev. the u-particle inhibits translation in vitro and binds to both capped and uncapped mrna's. it is spherical, 12 nm in diameter, and is composed of multiple copies of two polypeptide subunits having molecular weights of 23,000 and 25,000 which do not appear to be glycosylated or phosphorylated. u-particles are capable of inhibiting mrna translation in vitro.	1994	8032261
cardioviral poly(c) tracts and viral pathogenesis.	mengovirus is a prototypical member of the cardiovirus genus of the family picornaviridae. the positive-strand rna genome is 7761 bases in length and encodes a polyprotein of 2293 amino acids. the 5' non-coding region (758 bases) contains an unusual homopolymeric poly(c) tract, which in the wild-type virus, has a sequence of c50uc10. we have discovered through genetic engineering that truncation or deletion of this poly(c) sequence yields infectious virus isolates that grow well in cell culture, ...	1994	8032283
social isolation modifies the response of mice to experimental mengo virus infection.	to investigate the effects of social isolation on host resistance male mice were housed either individually (ih) or in groups of four or five (gh). all animals were infected with mengom,l virus. incubation time (incub), duration of illness (ill), death rate (dr), histopathological changes, and serum corticosterone levels (cort) were recorded. first, the effect of ih starting 4 days prior to infection was studied in 5 different inbred strains. next, the effect of different ih length was examined, ...	1994	8193172
the cellular u-particle, whose synthesis is induced by mengovirus infection, is homologous to apoferritin.	mengo virus infection of mouse l-cells results in induction of the synthesis of a cellular protein-containing particle, 12 nm in diameter, which was designated u (boege et al. (1987) virology 159, 358-367). we have purified the u-particle from virus-infected cells by a series of chromatographic steps and found it to be composed of two polypeptide species (mw 23,000 and 25,000), present in a ratio of approximately 7:3. neither of these polypeptides is measurably glycosylated or phosphorylated and ...	1994	8259685
in vivo antiviral effects of pidotimod.	the effect of pretreatment with pidotimod ((r)-3-[(s)- (5-oxo-2-pyrrolidinyl)-carbonyl]-thiazolidine-4-carboxylic acid, pgt/1a, cas 121808-62-6) was evaluated in mice infected with two challenging doses of three different viruses. mengovirus, herpes simplex, influenza virus were used. the mice were treated 15 days before the virus challenge. the antiviral effect of pidotimod was evaluated as difference in survival time versus control groups challenged with viruses but not pretreated with pidotim ...	1994	7857337
encephalomyocarditis viruses with short poly(c) tracts are more virulent than their mengovirus counterparts.	we have constructed three cdna clones of encephalomyocarditis virus strain r (emcv-r) with poly(c) tracts of c4, c9, and c20. rna transcribed from these cdnas was infectious to hela cells, and the resultant viruses grew well in this system, albeit with plaque sizes that were proportional to the poly(c) length. when injected into mice, the progeny viruses were only slightly less pathogenic than emcv-r, and the observed degree of attenuation was not nearly as dramatic as for equivalent mengoviruse ...	1995	7884926
picornavirus-specific cd4+ t lymphocytes possessing cytolytic activity confer protection in the absence of prophylactic antibodies.	picornaviruses are a family of positive-strand rna viruses that are responsible for a variety of devastating human and animal diseases. an attenuated strain of mengovirus (vmc24) is serologically indistinguishable from the lethal murine wild-type mengovirus and encephalomyocarditis virus (emcv). immunogen-specific stimulation of vmc24-immune splenocytes in vitro demonstrates preferential activation of cd4+ lymphocytes. vmc24-immune splenocytes adoptively transferred to naive recipients conferred ...	1995	7609060
cytotoxic t cell response to mengo virus in mice: effector cell phenotype and target proteins.	the mengo virus specific cytotoxic t lymphocyte (ctl) response was investigated after intraperitoneal infection of mice with the attenuated mengo virus strain vmc24. a high level of ctl activity was detected in spleen cell cultures obtained from infected c3h/hej (h-2k) or c57bl/6 (h-2b) mice after a secondary in vitro stimulation with mengo virus-infected cells. the ctl activity, which was mhc class i-restricted, was shown to be mediated by cd8+ t cells. recombinant vaccinia viruses that express ...	1995	7636480
attenuated mengo virus: a new vector for live recombinant vaccines.	several features make mengo virus an excellent candidate for use as a vaccine vector. the virus has a wide host range, including rodents, pigs, monkeys, and most likely humans, and expresses its genome exclusively in the cytoplasm of the infected cell. stable attenuated strains exist which are deleted for part of the 5' noncoding region of the genome. here we report an attenuated mengo virus recombinant, vlcmg4, that encodes an immunodominant cytotoxic t-lymphocyte epitope of the lymphocytic cho ...	1995	7707549
foot-and-mouth disease virus lb proteinase can stimulate rhinovirus and enterovirus ires-driven translation and cleave several proteins of cellular and viral origin.	rhinovirus and enterovirus 2a proteinases stimulate translation initiation driven from the cognate internal ribosome entry segment (ires) (s. j. hambidge and p. sarnow, proc. natl. acad. sci. usa 89:10272-10276, 1992; h.-d. liebig, e. ziegler, r. yan, k. hartmuth, h. klump, h. kowalski, d. blaas, w. sommergruber, l. frasel, b. lamphear, r. rhoads, e. kuechler, and t. skern, biochemistry 32:7581-7588, 1993). given the functional similarities between the foot-and-mouth disease virus (fmdv) l prote ...	1995	7745693
characterization of mengo virus neutralization epitopes. ii. infection of mice with an attenuated virus.	a panel of five neutralizing monoclonal antibodies was generated from mice immunized with an attenuated strain of mengo virus. four of the antibodies were used to select mutants of mengo virus which were able to escape neutralization by the selecting antibody, but it was not possible to select mutants which could escape neutralization by the fifth antibody. the capsid coding region of the rna genome of each mutant was directly sequenced to identify the mutation(s) responsible for the neutralizat ...	1995	8525606
the effect of cytotoxic lymphocytes on contraction, action potential and calcium handling in cultured myocardial cells.	cytotoxic t lymphocytes are important in the pathogenesis of several disease states, yet the pathophysiology of the lymphocyte-myocyte interaction is not well known. we have developed in vitro viral and autoimmune models to study the physiological phenomena associated with this interaction. to produce these models, lymphocytes were obtained from adult rats injected either with mengo virus or autologous cardiac myocytes. cardiac myocytes from neonatal rats were then exposed to these lymphocytes. ...	1995	8540399
induction of ferritin synthesis in cells infected with mengo virus.	we have recently identified ferritin as a cellular protein particle whose synthesis is stimulated in mouse or human cells infected by the picornavirus mengo. immunoprecipitation of the particle from infected murine l929 cells showed a 4- and 6-fold increase in the intracellular concentrations of h and l apoferritin subunits, respectively. this differential expression altered the h/l subunit ratio from 3.0 in uninfected cells to 2.2 in mengo virus-infected cells. the induction is not due to an in ...	1996	8621669
mutational analysis of the mengovirus poly(c) tract and surrounding heteropolymeric sequences.	previously, we described three mengovirus mutants derived from cdna plasmids, containing shortened poly(c) tracts (c8, c12, and c13uc10), that exhibited strong attenuation for virulence in mice yet grew like wild-type virus in hela cells. thirteen additional mutants hav now been constructed and characterized. five of these differ only in poly(c) length, including one with a precise deletion of the tract. the other mutants bear deletions into the regions juxtaposing poly(c). studies with hela cel ...	1996	8627731
b cell epitopes of hiv type 1 p24 capsid protein: a reassessment.	the objective of the present study was to identify p24 antigenic domains recognized during natural human immunodeficiency virus type 1 (hiv-1) infection, the determination of the major epitopes of p24 having significant applications for both the improvement of diagnostic approaches and the development of vaccines. reactivity of 20 hiv-1-infected patients and 8 hiv-1-negative patients was analyzed using an enzyme-linked immunosorbent assay (elisa) developed with 45 overlapping synthetic pentadeca ...	1996	8679307
mengovirus leader is involved in the inhibition of host cell protein synthesis.	the presence of a leader peptide in picornaviruses is restricted to the cardiovirus and aphthovirus genera. however, the leader peptides of these two genera are structurally and functionally unrelated. the aphthovirus leader is a protease involved in viral polyprotein processing and host cell translation shutoff. the function of the cardiovirus leader peptide is still unknown. to gain an insight into the function of the cardiovirus leader peptide, a mengovirus leader peptide deletion mutant was ...	1996	8763999
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 ...	1996	8852413
inhibition of 2-5a synthetase expression by antisense rna interferes with interferon-mediated antiviral and antiproliferative effects and induces anchorage-independent cell growth.	it has been shown previously that the ifn-induced enzyme 2-5a synthetase is sufficient to induce antiviral and antiproliferative effects in transfected cells expressing the protein. in this study, the possibility that this enzyme is also essential in generating these biological activities was investigated. for this purpose, a plasmid, pmsas-neo, was constructed. this plasmid carries an active neomycin-resistant gene. in addition, it contains a metallothionein promoter fused to an inverted 180-bp ...	1996	8853892
tandem mengovirus 5' pseudoknots are linked to viral rna synthesis, not poly(c)-mediated virulence.	the rna genomes from the cardioviruses, hepatoviruses, and aphthoviruses encode two to five tandem pseudoknots within their 5' untranslated regions. these pseudoknots lie adjacent to a pyrimidine-rich sequence, which in cardio- and aphthoviruses takes the form of a homopolymeric poly(c) tract. seven deletion mutations within mengovirus pseudoknots pk(b) and pk(c) were created and characterized. tested in tissue culture, mengovirus genomes with alterations in pk(c) were viable but had small plaqu ...	1996	8892950
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 ...	1996	8972564
epitope mapping of monoclonal antibodies raised to recombinant mengo 3d polymerase.	the cdna coding sequence of the rna-dependent rna polymerase (3dpol) of mengovirus was cloned and expressed in a bacterial system. eleven monoclonal antibodies were raised against the recombinant mengo 3dpol (rm3d). all of them recognized the recombinant and the viral-induced form of the protein. the panel of monoclonals belonged to the igg1 and igg2a isotypes and were mapped to four different epitopes in the 3d molecule by competition assays. all monoclonals recognized mengo 3dpol in western bl ...	1996	8972569
a multivalent minigene vaccine, containing b-cell, cytotoxic t-lymphocyte, and th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen.	the development of safe and effective vaccines remains a major goal in the prevention, and perhaps treatment, of infectious diseases. ideally, a single vaccine would confer protection against several pathogens and would induce both cellular and humoral arms of the immune response. we originally demonstrated that two virus-specific cytotoxic t-lymphocyte (ctl) epitopes, from the same virus but presented by different major histocompatibility complex alleles, when linked in tandem as minigenes in a ...	1997	9032365
theiler's virus and mengo virus induce cross-reactive cytotoxic t lymphocytes restricted to the same immunodominant vp2 epitope in c57bl/6 mice.	c57bl/6 mice develop a virus-specific cytotoxic t-lymphocyte (ctl) response after intraperitoneal inoculation with either the da strain of theiler's virus or mengo virus, two members of the cardiovirus genus. these ctls contribute to viral clearance in the case of theiler's virus but do not protect the mice from the fatal encephalomyelitis caused by mengo virus. in this study we show that da and mengo virus-induced ctls are cross-reactive. the cross-reactivity is due to a conserved, h-2db-restri ...	1997	9188606
genetic analysis of mengovirus protein 2a: its function in polyprotein processing and virus reproduction.	to examine the functional requirements of mengovirus 2a for virus reproduction, a series of mutants with overlapping deletions within the 2a region of mengovirus, and two chimeric constructs in which 2a is replaced either by theiler's murine encephalomyelitis virus (tmev) 2a or by coxsackie b3 virus (cbv3) 2apro were generated. in vitro polyprotein synthesis showed that in both deletion mutants and the tmev 2a chimeric construct, viral 3c protease (3cpro)-mediated cleavage at the vp1-2a junction ...	1998	9460917
study of the immunogenicity of different recombinant mengo viruses expressing hiv1 and siv epitopes.	recombinant mengo viruses expressing heterologous genes have proven to be safe and immunogenic in both mice and primates, and to be able to induce both humoral and cellular immune responses (altmeyer et al., 1995, 1996). several recombinant mengo viruses expressing either a large region (aa 65-206) of the hiv1 nef gene product, or cytotoxic t lymphocyte (ctl) epitopic regions from the siv gag (aa 182-190), nef (aa 155-178) and pol (aa 587-601) gene products were engineered. the heterologous anti ...	1998	9561560
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, ...	1998	9562889
trans-encapsidation of a poliovirus replicon by different picornavirus capsid proteins.	a trans-encapsidation assay was established to study the specificity of picornavirus rna encapsidation. a poliovirus replicon with the luciferase gene replacing the capsid protein-coding region was coexpressed in transfected hela cells with capsid proteins from homologous or heterologous virus. successful trans-encapsidation resulted in assembly and production of virions whose replication, upon subsequent infection of hela cells, was accompanied by expression of luciferase activity. the amount o ...	1998	9733835
protection against lethal encephalomyocarditis virus infection in the absence of serum-neutralizing antibodies.	although the ability of serum-neutralizing antibodies to protect against picornavirus infection is well established, the contribution of cell-mediated immunity to protection is uncertain. using major histocompatibility complex class ii-deficient (rhabeta-/-) mice, which are unable to mediate cd4(+) t-lymphocyte-dependent humoral responses, we demonstrated antibody-independent protection against lethal encephalomyocarditis virus (emcv) infection in the natural host. the majority of rhabeta-/- mic ...	1998	9733845
genetically engineered mengo virus vaccination of multiple captive wildlife species.	encephalomyocarditis virus (emcv), has caused the deaths of many species of animals in zoological parks and research institutions. the audubon park zoo, (new orleans, louisiana, usa) attempted vaccination of several species with a killed emcv vaccine with mixed results. this paper reports an attempt at vaccination against emcv using a genetically engineered, live attenuated mengo virus (vmc0) at the audubon park zoo and miami metro zoo, (miami, florida, usa) from december 1996 to june 1997. seve ...	1999	10231768
selective irreversible inactivation of replicating mengovirus by nucleoside analogues: a new form of viral interference.	we describe the selective irreversible inhibition of mengovirus growth in cultured cells by a combination of two pyrrolopyrimidine nucleoside analogues, 5-bromotubercidin (brtu) and tubercidin (tu). at a concentration of 5 microgram/ml, brtu reversibly blocked the synthesis of cellular mrna and rrna but did not inhibit either mengovirus rna synthesis or multiplication. brtu is a potent inhibitor of adenosine kinase, and low concentrations of brtu (e.g., 0.5 microgram/ml), which did not by themse ...	1999	10400738
a coding rna sequence acts as a replication signal in cardioviruses.	theiler's virus and mengo virus are representatives of the cardiovirus genus within the picornavirus family. their genome is an 8-kilobase long positive strand rna molecule. this rna molecule plays three roles in infected cells: it serves as a messenger rna, acts as a template for genome replication, and is encapsidated to form progeny virions. we observed that a cis-acting signal required for replication of theiler's virus was contained within a 130-nt stretch of the region encoding the capsid ...	1999	10500216
mengovirus and encephalomyocarditis virus poly(c) tract lengths can affect virus growth in murine cell culture.	many virulent aphthoviruses and cardioviruses have long homopolymeric poly(c) tracts in the 5' untranslated regions of their rna genomes. a panel of genetically engineered mengo-type cardioviruses has been described which contain a variety of different poly(c) tract lengths. studies of these viruses have shown the poly(c) tract to be dispensable for growth in hela cells, although the relative murine virulence of the viruses correlates directly and positively with tract length. compared with wild ...	2000	10708422
characterization of genetically engineered mengoviruses in mice.	we have shown that genetically engineered mengoviruses containing artificially shortened 5' noncoding poly(c) tracts (e.g., c0 or c13uc10) are dramatically attenuated in adult swiss/icr mice when compared to wild-type virus or to a genetically engineered virus containing a wild-type length poly(c) tract (c44uc10). to explore further the relationship between poly(c) tracts and virulence, we have conducted more extensive characterizations of several engineered viruses in the murine model. both sho ...	2000	10733166
evaluation of the antiviral activity of an aqueous extract from phyllanthus orbicularis.	the antiviral and cytotoxic activity of phyllanthus orbicularis, a member of the euphorbiaceae, was evaluated in tissue culture. an aqueous extract made from leaves and stems of this plant exhibited selective antiviral indexes of 12.3 and 26 against bovine herpesvirus type 1 and herpes simplex virus type 2, respectively, showing no selective antiviral activity against adenovirus type 5 and mengovirus. incubation with this plant extract during cell culture infection, impaired the productive repli ...	2000	10967489
broad antiviral activity in tissues of crustaceans.	innate antiviral substances occur in vertebrates and may function as host defenses. virus infections are common among invertebrates, but little is known about the ability of invertebrates to control viral infections. pre-existing antiviral substances may be particularly important, since invertebrates lack the antiviral defense conferred by specific immunity. in our study, we found that tissue extracts of blue crab (callinectes sapidus), shrimp (penaeus setiferus), and crayfish (procambarus clark ...	2000	11080539
translation and replication of human rhinovirus type 14 and mengovirus in xenopus oocytes.	we have previously shown that xenopus oocytes require coinjection of both poliovirus rna and hela cell extracts to support a complete cycle of viral replication yielding high levels of infectious viral particles. this novel system provides a tool for identifying host factors and for biochemically dissect individual steps that lead to virus production. here we demonstrate that xenopus oocytes are able to support replication of other picornaviruses such as human rhinovirus 14 and mengovirus. unlik ...	2000	11090201
phenotypic characterization of three phylogenetically conserved stem-loop motifs in the mengovirus 3' untranslated region.	an alignment of cardiovirus sequences led to the prediction of three conserved stem-loops in the 3' untranslated region (utr) of mengovirus. deletions of each stem were engineered in mengovirus cdnas and also in mengovirus replicons, in which part of the viral capsid sequences were replaced with the firefly luciferase gene. the effect of deletion on rna infectivity and plaque phenotype was evaluated after transfection of viral transcripts into hela cells or by luciferase assays of cellular extra ...	2001	11238838
encephalomyocarditis and mengo viruses productively infect murine t-lymphocyte cell lines but not fresh ex vivo derived t lymphocytes.	encephalomyocarditis virus (emcv) and mengo virus are highly virulent murine cardioviruses that are found in abundant quantities in the spleen and lymph nodes after infection. t lymphocytes are pivotal mediators of humoral and cellular immunity against cardioviral challenge, and are highly suspect candidates of emcv and mengo virus infection. we found t lymphocyte-like cell lines ctll-2, el-4, ly1+2/9, and lbrm33 were susceptible to productive viral infection and exhibited cytopathology after in ...	2002	11952137
the mengovirus leader protein suppresses alpha/beta interferon production by inhibition of the iron/ferritin-mediated activation of nf-kappa b.	in our studies on the biological function of the mengovirus leader protein, we identified a casein kinase ii (ck-2) phosphorylation site in the protein. here we report that the mengovirus leader protein can be phosphorylated by ck-2 in vitro. expression of a recombinant leader protein in which the consensus ck-2 sequence around threonine 47 was disturbed resulted in a mutant protein that could no longer be phosphorylated. the ck-2 consensus sequence was modified by site-directed mutagenesis and ...	2002	12208945
a new look at viruses in type 1 diabetes.	type 1 diabetes (t1d) results from the destruction of pancreatic beta cells. genetic factors are believed to be a major component for the development of t1d, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that nongenetic factors play an important role in the expression of the disease. viruses are one environmental factor that is implicated in the pathogenesis of t1d. to date, 14 different viruses have been reported to be associated with ...	2003	12592641
genetic analysis of a theiler-like virus isolated from rats.	although cardioviruses related to theiler's murine encephalomyelitis virus (tmev) appear to be common in mice and rats, few tmev isolates have been obtained from rat colonies. in 1991, a cardiovirus isolate designated ngs910 was obtained from sentinel rats exposed to cage bedding previously used by adult rats that were tmev seropositive, but had never manifested clinical signs of disease. to determine to which group and subgroup of cardiovirus this virus belongs, the sequence of the viral genome ...	2003	12784854
a wild-type porcine encephalomyocarditis virus containing a short poly(c) tract is pathogenic to mice, pigs, and cynomolgus macaques.	previous studies using wild-type encephalomyocarditis virus (emcv) and mengo virus, which have long poly(c) tracts (61 to 146 c's) at the 5' nontranslated region of the genome, and variants of these viruses genetically engineered to truncate or substitute the poly(c) tracts have produced conflicting data on the role of the poly(c) tract in the virulence of these viruses. analysis of the nucleotide sequence of an emcv strain isolated from an aborted swine fetus (emcv 30/87) revealed that the viru ...	2003	12915530
genetic stability of attenuated mengovirus vectors with duplicate primary cleavage sequences.	short poly(c)-tract mengoviruses have proven vaccine efficacy in many species of animals. a novel vector for the delivery of foreign proteins was created by insertion of a second autoproteolytic primary cleavage cassette linked to a multiple cloning site (mcs) into an attenuated variant of mengo. nineteen cdnas from foreign sequences that ranged from 39 to 1653 bases were cloned into the mcs. the viral reading frame was maintained and translation resulted in dual, autocatalytic excision of the f ...	2003	12919752
encephalomyocarditis viral protein 2a localizes to nucleoli and inhibits cap-dependent mrna translation.	panels of monoclonal antibodies were raised against viral non-structural proteins of encephalomyocarditis virus (emcv) and used to probe infected cells in laser confocal microscopy experiments and western analyses. surprisingly, all mengovirus and emcv-infected cells showed strong targeting of protein 2a, 3b(vpg), 3c(pro), and 3d(pol) signals to cellular nuclei, in particular to nucleoli, from the earliest times of infection. viral capsid proteins (1ab, 1c, and 1d) and other non-structural prote ...	2003	12921995
characterization of interferon-alpha 13, a novel constitutive murine interferon-alpha subtype.	type-i interferons (ifns), also called ifns-alpha/beta, are a family of cytokines induced by viral infection and are primarily involved in antiviral defense of the cells. ifns-alpha/beta were also reported to be produced constitutively at low levels in mouse and human cells. these so-called endogenous or constitutive ifns are thought to exert important homeostatic functions in the uninfected host. by searching ifn genes that were not repressed by the leader protein of theiler's virus, we identif ...	2003	12930842
expression of a foreign gene by stable recombinant influenza viruses harboring a dicistronic genomic segment with an internal promoter.	based on the observation that an internally located 3' promoter sequence can be functional (r. flick and g. hobom, virology, 1999, 262(1), 93-103), we generated transfectant influenza a viruses harboring a dicistronic segment containing the cat gene (660 nt) or a fragment of the mengo virus vp0 capsid gene (306 nt) under the control of a duplicated 3' promoter sequence. despite slightly reduced na expression, the transfectant viruses replicated efficiently and proved to be stable upon both seria ...	2003	12951036
an adenine-to-guanine nucleotide change in the ires sl-iv domain of picornavirus/hepatitis c chimeric viruses leads to a nonviable phenotype.	the inability for the internal ribosomal entry site (ires) of hepatitis c virus (hcv) to be readily studied in the context of viral replication has been circumvented by constructing chimeras such as with poliovirus (pv), in which translation of the genome polyprotein is under control of the hcv ires. during our attempts to configure the pv/hcv chimera for our drug discovery efforts, we discovered that an adenine- (a) to-guanine (g) change at nt 350 in domain iv of the hcv ires resulted in a nonv ...	2003	14698672
dipyridamole reversibly inhibits mengovirus rna replication.	dipyridamole is an effective inhibitor of cardiovirus growth in cell culture. the effects of dipyridamole on mengovirus replication in vivo and in vitro were examined in the hope the drug could be used as an experimental analog of the poliovirus inhibitor guanidine. guanidine selectively inhibits poliovirus rna synthesis but not rna translation, and as such, has been a valuable research tool. although guanidine does not inhibit cardiovirus infection, a compound with similar discriminatory charac ...	2005	16103157
cardiovirus leader proteins are functionally interchangeable and have evolved to adapt to virus replication fitness.	the leader (l) proteins encoded by picornaviruses of the genus cardiovirus [theiler's murine encephalomyelitis virus (tmev) and encephalomyocarditis virus (emcv)] are small proteins thought to exert important functions in virus-host interactions. the l protein of persistent tmev strains was shown to be dispensable for virus replication in vitro, but crucial for long-term persistence of the virus in the central nervous system of the mouse. the phenotype of chimeric viruses generated by exchanging ...	2006	16603526
synthesis of the allergen ovomucoid by a replicating mengo virus.	interferons induced by viral infections can have powerful immuno- modulatory effects, and several epidemiologic studies have found an association between certain viral infections and reduced prevalence of allergy. we hypothesized that allergenic proteins could be synthesized by a replicating virus, and this construct could be useful as an immunomodulator. to test this hypothesis, we cloned an allergenic protein (ovomucoid [ovm]) into a murine picornavirus (mengo virus) vector. this plasmid has a ...	2006	16732496
development, evaluation, and standardization of a real-time taqman reverse transcription-pcr assay for quantification of hepatitis a virus in clinical and shellfish samples.	a standardized real-time reverse transcription-pcr (rt-pcr) assay has been developed for an accurate estimation of the number of genome copies of hepatitis a virus (hav) in clinical and shellfish samples. real-time procedures were based on the amplification of a fragment of the highly conserved 5' noncoding region and detection through an internal fluorescent probe, including taqman and beacon chemistries, in one- and two-step rt-pcr formats. the best performance in terms of sensitivity and repr ...	2006	16751488
genomic analysis of two porcine encephalomyocarditis virus strains isolated in china.	two strains of encephalomyocarditis virus (emcv), designated bjc3 and hb1, were isolated from an aborted fetus and the heart tissue of a dead piglet that had pericardial fluid, respectively. the complete genomic sequences of the two viruses were determined and analyzed. the size of the genomes of bjc3 and hb1 were 7746 and 7735 nucleotides, respectively, including poly(a) tails. comparative analysis with the genomic sequences of other emcv strains showed that bjc3 and hb1 shared higher identity ...	2007	17294091
pdtc inhibits picornavirus polyprotein processing and rna replication by transporting zinc ions into cells.	previously, it was shown that pyrrolidine dithiocarbamate (pdtc) inhibits proteolytic polyprotein processing and replication of human rhinovirus by transporting metal ions into cells. here, it is shown that pdtc also inhibits replication of two other picornaviruses: coxsackievirus b3 (cvb3), a closely related virus that belongs to the genus enterovirus, and mengovirus, an encephalomyocarditis virus strain that belongs to the genus cardiovirus, and that this inhibition is due to the dithiocarbama ...	2007	17374764
significance of the c-terminal amino acid residue in mengovirus rna-dependent rna polymerase.	replication of picornavirus genomes is accomplished by the virally encoded rna-dependent rna polymerase (rdrp). although the primary structure of this enzyme exhibits a high level of conservation, there are several significant differences among different picornavirus genera. in particular, a comparative alignment indicates that the c-terminal sequences of cardiovirus rdrp (known also as 3d(pol)), are 1-amino-acid residue (arginine or tryptophan) longer than that of the enterovirus or rhinovirus ...	2007	17467026
increased antiviral activity of microscale-purified huifn alpha 8 (human interferon alpha 8) over huifn alpha 2b in hep-2 cells challenged with mengo virus.	human proteins are not routinely expressed at high levels in escherichia coli for, among other reasons, different codon usage. several purification procedures have been applied to recover recombinant proteins for further biological characterization. however, the vast majority involve costly chromatography procedures. in the present study, both (hu)ifn(alpha 2b) (human interferon alpha 2b) and (hu)ifn(alpha 8) were expressed efficiently in e. coli bl21-codonplus-ril. subsequently, both recombinan ...	2007	17523917
evaluation of removal of noroviruses during wastewater treatment, using real-time reverse transcription-pcr: different behaviors of genogroups i and ii.	noroviruses, an important cause of gastroenteritis, are excreted by infected individuals and are therefore present in wastewater. we quantified norovirus genogroup i (gi) and gii in wastewater at different locations in france and evaluated removal by a range of treatment types, including basic (waste stabilization pond), current industry standard (activated sludge), and state-of-the-art (submerged membrane bioreactor) treatments. noroviruses were quantified using real-time reverse transcription- ...	2007	17933913
the mengovirus leader protein blocks interferon-alpha/beta gene transcription and inhibits activation of interferon regulatory factor 3.	viral infection of mammalian cells triggers the synthesis and secretion of type i interferons (i.e. ifn-alpha/beta), which induce the transcription of genes that cause cells to adopt an antiviral state. many viruses have adapted mechanisms to evade ifn-alpha/beta-mediated responses. the leader protein of mengovirus, a picornavirus, has been implicated as an ifn-alpha/beta antagonist. here, we show that the leader inhibits the transcription of ifn-alpha/beta and that both the presence of a zinc f ...	2007	17991048
delivery of mengovirus-derived rna replicons into tumoural liver enhances the anti-tumour efficacy of a peripheral peptide-based vaccine.	hepatocellular carcinoma is a deadly cancer with growing incidence for which immunotherapy is one of the most promising therapeutic approach. peptide-based vaccines designed to induce strong, sustained cd8+ t cell responses are effective in animal models and cancer patients. we demonstrated the efficacy of curative peptide-based immunisation against a unique epitope of sv40 tumour antigen, through the induction of a strong cd8+ t cell-specific response, in our liver tumour model. however, as in ...	2008	18256833
nmr structure of the mengovirus leader protein zinc-finger domain.	the leader protein is a defining feature of picornaviruses from the cardiovirus genus. this protein was recently shown to inhibit cellular nucleocytoplasmic transport through an activity mapped to its zinc-binding region. here we report the three-dimensional solution structure determined by nuclear magnetic resonance (nmr) spectroscopy of this domain (residues 5-28) from mengovirus. the domain forms a chcc zinc-finger with a fold comprising a beta-hairpin followed by a short alpha-helix that can ...	2008	18291103
detection of norovirus genotype i.3b and ii.4 in bioaccumulated blue mussels using different virus recovery methods.	noroviruses (novs) are the most common non bacterial human pathogens associated with shellfish borne gastroenteritis. norovirus detection is based on molecular procedures such as reverse transcriptase (rt)-pcr. a variety of methods have been developed to extract viral rna from complex shellfish matrixes and to reduce the level of rt-pcr inhibitors. the present study had three objectives: 1) determine the most appropriate sample treatment protocol for detection of novs in mussels, 2) examine whet ...	2008	18640736
antiviral activity of the zinc ionophores pyrithione and hinokitiol against picornavirus infections.	we have discovered two metal ion binding compounds, pyrithione (pt) and hinokitiol (hk), that efficiently inhibit human rhinovirus, coxsackievirus, and mengovirus multiplication. early stages of virus infection are unaffected by these compounds. however, the cleavage of the cellular eukaryotic translation initiation factor eif4gi by the rhinoviral 2a protease was abolished in the presence of pt and hk. we further show that these compounds inhibit picornavirus replication by interfering with prop ...	2009	18922875
mengovirus-induced rearrangement of the nuclear pore complex: hijacking cellular phosphorylation machinery.	representatives of several picornavirus genera have been shown previously to significantly enhance non-controllable bidirectional exchange of proteins between nuclei and cytoplasm. in enteroviruses and rhinoviruses, enhanced permeabilization of the nuclear pores appears to be primarily due to proteolytic degradation of some nucleoporins (protein components of the pore), whereas this effect in cardiovirus-infected cells is triggered by the leader (l) protein, devoid of any enzymatic activities. h ...	2009	19144712