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hemagglutinin mutations related to attenuation and altered cell tropism of a virulent avian influenza a virus.the h5 hemagglutinin (ha) of a highly virulent avian influenza virus, a/turkey ontario/7732/66 (h5n9), was previously shown to have five neutralizing epitopes, and escape mutants within one epitope (group 1) were markedly attenuated (m. philpott, b. c. easterday, and v. s. hinshaw, j. virol. 63:3453-3458, 1989). to define the genetic changes related to these antigenic and biologic properties, the ha genes of mutants within each of the epitope groups were sequenced by using the polymerase chain r ...19902335822
effect of immunomodulator adamantylamide dipeptide on antibody response to influenza subunit vaccines and protection against aerosol influenza infection.adamantylamide dipeptide (addp) is a novel synthetic compound combining the antiviral properties of amantadine and the essential adjuvant activity of immunomodulator muramyl dipeptide. mice were immunized with influenza a/taiwan/1/86 (h1n1), a/sichuan/2/87 (h3n2) and influenza b/beijing/1/87 subunit vaccines containing addp or aluminium hydroxide (al(oh)3). induction of homologous haemagglutination-inhibition (hi) antibodies and correlation to protection against lethal aerosol influenza a/pr/8/3 ...19902336875
introduction of site-specific mutations into the genome of influenza virus.we succeeded in rescuing infectious influenza virus by transfecting cells with rnas derived from specific recombinant dnas. rna corresponding to the neuraminidase (na) gene of influenza a/wsn/33 (wsn) virus was transcribed in vitro from plasmid dna and, following the addition of purified influenza virus rna polymerase complex, was transfected into mdbk cells. superinfection with helper virus lacking the wsn na gene resulted in the release of virus containing the wsn na gene. we then introduced f ...19902339122
influenza virus infection, ozone exposure, and fibrogenesis.oxidant exposure following chemically induced lung injury exacerbates the tendency to develop pulmonary fibrosis. influenza virus pneumonitis causes severe acute lung damage that, upon resolution, is followed by a persistent alveolitis and parenchymal changes characterized by patchy interstitial pneumonia and collagen deposition in the affected areas. to determine whether oxidant exposure exacerbates the virus-induced alveolitis and residual lung damage, mice were infected by aerosol inhalation ...19902339849
presentation of viral antigen controlled by a gene in the major histocompatibility complex.we describe a mutant human cell line (lbl 721.174) that has lost a function required for presentation of intracellular viral antigens with class i molecules of the major histocompatibility complex (mhc), but retains the capacity to present defined epitopes as extracellular peptides. the cell also has a defect in the assembly and expression of class i mhc molecules, which we show can be restored by exposure of the cells to a peptide epitope. this phenotype suggests a defect in the association of ...19902342577
[clinical and immunologic effects following oral immunization against influenza in children in day care and infection susceptible young children].57 infants and small children (9 months - 3.1 years) were orally immunized by an inactivated influenza vaccine (mississippi 1/85; dosage: 110 micrograms ha); the control group (n = 15) received placebo. after three months the influenza specific ig-concentrations of serum and secretions demonstrated a controverse course: specific igg (serum) decreased and specific iga (nasale secretions) increased statistically significant (p less than 0.025), especially in children suffering from frequently rela ...19902342818
[the results of using the molecular hybridization of nucleic acids in the complex study of nasopharyngeal smears from patients with influenza and other acute respiratory diseases].a complex study of samples obtained from patients with influenza and other acute respiratory diseases has revealed that the laboratory methods used in this study can be rated in the following order according to their sensitivity: isolation of the virus in chick embryos, analysis of seroconversions in the hemagglutination inhibition test, immunofluorescent determination of viral antigens, determination of viral antigens by enzyme immunoassay (eia), detection of rna-containing viral structures by ...19902343679
fusion characteristics of influenza c viruses.a number of different influenza c virus strains were tested for their fusion properties using a resonance energy assay which allows direct monitoring of fusion between virus membranes and artificial lipid vesicles. the fusion ph of various strains was found to range between 5.6 and 6.1. haemolytic activity of the different strains with chicken erythrocytes was observed at slightly lower ph values and varied between 5.1 and 5.7. studies of the kinetics of influenza c virus fusion showed distinct ...19902345368
structural variation occurring in the hemagglutinin of influenza virus a/turkey/oregon/71 during adaptation to different cell types.the influenza virus a/turkey/oregon/71 (h7n3) has been adapted to grow in mdck or chicken embryo cells (cec) in the absence of trypsin. changes occurred in the biological properties of the virus variants selected, depending on the cell type used for adaptation. they coincided with enhanced hemagglutinin (ha) activation by intracellular proteolytic cleavage. in the case of mdck cell selected variants growth, plaque formation, and ha cleavability were restricted to this cell type, whereas the cec- ...19902345964
sequence of an influenza virus hemagglutinin determined directly from a clinical sample.the sequence of the ha1 region of the hemagglutinin gene of an influenza virus has been determined without growing the virus in eggs or in cultured cells. the virus used was an h1 strain of influenza a from a clinical specimen taken from a patient in 1987. rna was extracted directly from virus that had been sedimented out of the transport medium in which the sample had been stored. dna copies of the hemagglutinin gene, obtained by reverse transcription, were then amplified by the polymerase chai ...19902349225
the phosphorylation of the integral membrane (m1) protein of influenza virus.the phosphorylation of the internal and integral membrane (m1) protein of influenza virus was studied. four points can be made based on the data: (1) the m1 contains at least two moles of phosphate per mole of m1. (2) phosphorylation of m1 is conserved between influenza a, b and c viruses. other characteristics of the m1 are also conserved, such as solubility in organic solvent, heterogeneity and ability to partition into lipid vesicles. (3) m1 is phosphorylated in cells infected with a vaccinia ...19902349833
comparison of inactivated, live and recombinant dna vaccines against influenza virus in a mouse model.the protective efficacy of influenza hemagglutinin expressed from recombinant vaccinia virus was compared with that induced by inactivated or infectious influenza vaccines. intraperitoneal and intranasal routes of vaccination were compared. all the vaccines except the intranasally administered, inactivated vaccine induced detectable levels of neutralizing and hemagglutination-inhibiting antibodies in the serum of mice at 28 days postvaccination. immunization with any of the intranasally administ ...19902349834
inhibition of influenza virus a/wsn replication by a trypsin inhibitor, 6-amidino-2-naphthyl p-guanidinobenzoate.a trypsin inhibitor, 6-amidino-2-naphthyl p-guanidinobenzoate (futhan) reduced both the number and size of plaques of influenza virus a/wsn/33 (h1n1) that can grow without trypsin treatment in mdck cells. the resulting virus particles with uncleaved hemagglutinin (ha) in the presence of futhan was activated to produce infectious virions by trypsin treatment. uncleaved ha of wsn virus grown in the presence of futhan was found to be accumulated by protein analysis of wsn virus labeled biosynthetic ...19902350338
biological and immunological characterization of influenza virus haemagglutinin expressed from the haemagglutinin locus of vaccinia virus.plasmid vectors were constructed to facilitate the insertion and expression of a foreign gene in the haemagglutinin (ha) gene locus of vaccinia virus. five unique cloning sites adjacent to the p7.5 promoter of vaccinia virus permit the rapid insertion of a foreign sequence coding for a protein into these plasmids. this vector system provides a simple procedure to select recombinant viruses because they can be readily identified on the basis of their ha-defective phenotype. recombinant vaccinia v ...19902351957
enhancement of dth response by cholera toxin b subunit inoculated intranasally together with influenza ha vaccine.the effects of b subunit of cholera toxin (ctb) on delayed-type hypersensitivity (dth) response to influenza vaccine derived from influenza virus a/pr/8/34 (pr-8, hlnl) virus were investigated in b10 mice that were immunized intranasally with both influenza vaccine and ctb. the result showed that intranasal inoculation of this combination augmented dth response to influenza vaccine, which reached its peak 6 days after inoculation, and also induced accelerated dth response upon a second inoculati ...19902352500
genetic drift of equine 2 influenza a virus (h3n8), 1963-1988: analysis by oligonucleotide mapping.comparative analysis by rna oligonucleotide fingerprints of total genomic rna as well as the individual rna segments of equine 2 influenza a virus strains from 1963, 1968, 1979, 1984, 1987 and 1988 revealed genetic diversity. strains from the epizootic outbreak during 1978-1979 showed minor differences among their genomes. the swedish isolates from 1979 up to 1988 showed increasing genomic heterogeneity indicating genetic drift.19902353444
influenza-specific elisa iga and igg predict severity of influenza disease in subjects prescreened with hemagglutination inhibition.four influenza a challenge studies were performed over a period of three years using the same dose of one virus pool. the first three studies were conducted two influenza seasons apart from the last study. in all four studies only subjects with screening hemagglutination inhibition (hai) antibody titers less than or equal to 1:8 in sera were accepted as study subjects. the rate of infection after influenza challenge was 96% (25 of 26) in the first three studies, and only 73% (8 of 11) in the las ...19902353803
antigenic reactivity and electrophoretic migrational heterogeneity of the three polymerase proteins of type a human and animal influenza viruses.antigenic reactivity of the three polymerase proteins pb1, pb2, and pa of type a influenza viruses of animal and human origin were analysed by radioimmunoprecipitation using monospecific antisera. each of the polymerase monospecific antisera made against the polymerase proteins of the human a/wsn/33 (h1n1) influenza virus reacted efficiently with the homologous proteins of all the known thirteen ha subtype viruses of avian influenza virus, three subtypes of human influenza virus, swine and equin ...19902353872
lack of persistence of influenza virus genetic information in ducks.clearance of infectious virus and rna occurred concurrently after oral infection of ducks with influenza virus. there was no evidence from polymerase chain reaction (pcr) analysis of the hemagglutinin (ha) gene for persistence of viral genetic information. no detectable rna was found in the spleen indicating processing of antigen near the site of replication.19902353873
purification and molecular structure of rna polymerase from influenza virus a/pr8.the rna-dependent rna polymerase of influenza virus a/pr/8 was isolated from virus particles by stepwise centrifugation in cesium salts. first, rnp (viral rna-np-p proteins) complexes were isolated by glycerol gradient centrifugation of detergent-treated viruses and subsequently np was dissociated from rnp by cesium chloride gradient centrifugation. the p-rna (p proteins-viral rna) complexes were further dissociated into p proteins and viral rna by cesium trifluoroacetate (cstfa) gradient centri ...19902358436
age-related decline in interleukin 2 production in response to influenza vaccine.articles in the recent literature document an abnormal antibody response in elderly persons to influenza vaccination. several studies have presented evidence to show that immune dysfunction in aged mice and humans may be due to a defect in the production of interleukin 2 (il2) by helper t cells (th). cultures of peripheral blood mononuclear cells (pbmc) were prepared from blood samples taken at eight weeks after vaccination (0.5 ml of armand-frappier, 15 micrograms/0.5 ml each of a/taiwan/1/86, ...19902358627
resistance to h-2-restricted but not to allo-h2-specific graft and cytotoxic t lymphocyte responses in lymphoma mutant.the lymphoma mutant rma-s escaped graft rejection after transplantation over a minor histocompatibility barrier, whereas it was rejected in h-2 allogeneic mice. the parental control line was rejected in both situations. the mutant, which had been selected against mhc class i molecules retained 5 to 10% of the wild-type h-2db, kb, and beta 2-microglobulin expression on the cell surface. it remained sensitive to allo-h-2b ctl in vitro, but was completely resistant to minor histocompatibility antig ...19902358681
[anti-influenza effect of bacterial rnase and the pharmacokinetic basis of its administration in experimental studies].anti-influenzal action of bacterial and pancreatic rnaases was studied. it was shown in ovo that the rnaases had distinct virus inhibiting activity with respect to various strains of the grippe a virus and did not practically differ by their activity from remantadin but unlike it had inhibitory action on the grippe b virus. the anti-influenzal activity of bacterial rnaase in contrast to pancreatic one was detected not only in experiments with developing chick embryos but also in albino mice with ...19902360851
influenza in patients with human immunodeficiency virus infection.although patients infected with human immunodeficiency virus (hiv) might be expected to have more severe illness due to influenza virus infection than normal persons, the course of influenza in such patients has not been well delineated. we describe six consecutive hiv-infected patients at san francisco general hospital in whom influenza virus was isolated from induced sputum or bronchoalveolar lavage specimens between december 1988 and march 1989. although neither clinical presentation of influ ...19902361409
synthesis and antiviral activity of metabolites of rimantadine.the hydroxy metabolites of rimantadine (3-5) were synthesized and compared to amantadine (1) and rimantadine (2) for their ability to inhibit the replication of influenza viruses in vitro. all three metabolites were inhibitory to wild-type influenza a viruses (h3n2 and h1n1). in particular, 2-hydroxyrimantadine (3) showed similar activity to amantadine, but the 3- and 4-hydroxy metabolites (4 and 5, respectively), both of which are found in rimantadine-treated patients, showed only modest inhibi ...19902362279
[study of influenza virus hemagglutinin h3 avidity using monoclonal antibodies].the results of a comparative study of the features of antigenic determinants of avid and non-avid variants of influenza virus hemagglutinin h3 and of the influence of the mode of antigen presentation on the degree of its avidity are presented. the avidity of influenza virus hemagglutinin was shown to be determined by the capacity of individual antigenic determinants to interaction with antibodies. the antigenic determinants of avid hemagglutinin possessing a high functional activity in interacti ...19902363270
[comparative characteristics of spherical and filamentous virions of influenza virus type a].an analysis of fractions of a reassortant of a/wsn/33 and a/duck/hochimin/014/78 strains enriched with spherical and filamentous virions showed that spherical and filamentous virus particles differed by sucrose density gradient. the relative content of nucleocapsid protein in filamentous virions was slightly lower than in spherical ones which might be due to different volume/surface ratio of these particles. the results of uv-inactivation of filamentous and spherical virions suggest that the fil ...19902363271
relation between susceptibility to rubellavirus infection in pregnant women and decreased immune responsiveness. 19902363297
comparison of intranasal inoculation of influenza ha vaccine combined with cholera toxin b subunit with oral or parenteral vaccination.the antibody responses to influenza virus a/pr/8/34 ha vaccine and protection against virus challenge in mice given the vaccine together with the b subunit of cholera toxin (ctb) intranasally were compared with those in mice given the vaccine with ctb perorally, intraperitoneally or subcutaneously. intranasal vaccination induced remarkably higher levels of antiviral iga antibodies in both respiratory washings and serum than did other routes of vaccination. the titres of antiviral igg antibodies ...19902363302
reye's syndrome: a case control study of medication use and associated viruses in australia.the records of 49 cases of reye's syndrome at three pediatric hospitals in australia are compared with 94 controls. the diagnosis of reye's syndrome was confirmed pathologically in 42 of 49 cases (86%). aspirin or salicylate ingestion occurred in only 4 (8%), and paracetamol (acetaminophen) ingestion in 12 (24%) (p greater than 0.05 by chi-square analysis). of the controls, 3 (3%) had taken aspirin and 39 (41%) had taken paracetamol. associated viruses included paramyxoviruses, picornaviruses, r ...19902364532
mapping mutations in influenza a virus resistant to norakin.to elucidate the mode of action of norakin against influenza a virus we sequenced the hemagglutinin gene of 11 norakin-resistant mutants. resistance was coupled with 1-3 amino acid exchanges. the majority of mutations was localized in the ha2 polypeptide and was mostly associated with changes in charge or polarity of the amino acids. the amino acid substitutions are discussed in the context of the 3d structure of x31 hemagglutinin considered to be representative of the influenza hemagglutinins. ...19902365087
kinins are generated in nasal secretions during influenza a infections in ferrets.infection of ferrets with influenza a virus results in a disease syndrome that is similar to that observed in humans. to examine the pathophysiology of this disease, ferrets were challenged with either h1n1 influenza virus or placebo. sign scores and rectal temperatures were recorded periodically during the 9 days after infection. nasal lavages were also collected during this time period and the content of kinins, histamine, cells, and total protein in these lavages was assessed. in infected ani ...19902368965
avian influenza viruses from migratory and resident ducks of coastal louisiana.cloacal and tracheal swabs were collected from 1389 hunter-killed ducks in cameron parish, louisiana, during the 1986 and 1987 waterfowl seasons. twenty-eight avian influenza viruses (aivs) were isolated from 605 blue-winged teal (anas discors), 75 mottled ducks (a. fulvigula), 375 gadwalls (a. stepera) and 334 green-winged teal (a. crecca). prevalence estimates of aiv in ducks sampled during september, november, and december through january were 3.1%, 2.0%, and 0.4%, respectively. differences i ...19902369380
elevated viral antibody titres in spontaneous abortion.to assess the possible role of virus infections in spontaneous abortion we undertook a prospective study of three groups of patients: women who had a spontaneous abortion; women seen in the antenatal booking clinic; and those undergoing therapeutic termination of pregnancy. venous blood was taken for antibody detection, cervical swabs for virus isolation, and in the cases of spontaneous and therapeutic abortion products of conception were sent for virus culture. the infectious agents studied wer ...19902369525
infection enhancement of influenza a h1 subtype viruses in macrophage-like p388d1 cells by cross-reactive antibodies.the contribution of cross-reactive hemagglutination inhibition (hi) antibodies to infection enhancement of influenza a h1 subtype nws virus and two antigenic drift strains was investigated in a macrophage-like cell line p388d1. when p388d1 cells, previously treated with neuraminidase (na) to remove the viral receptors, were infected with nws virus exposed to rabbit antiviral immunoglobulin (igg) showing various levels of cross-hi titers, virus yields were enhanced in the presence of a subneutral ...19902370521
chlamydia pneumoniae strain twar, mycoplasma pneumoniae, and viral infections in acute respiratory disease in a university student health clinic population.clinical and serologic data were collected on 667 university of washington students who presented to the david hall student health center between 1983 and 1987 with acute respiratory disease. sera were tested for evidence of acute or past infections with chlamydia pneumoniae strain twar, chlamydia trachomatis, mycoplasma pneumoniae, influenza a virus, influenza b virus, adenovirus, and respiratory syncytial virus. pharyngeal swab specimens were cultured for c. pneumoniae and c. trachomatis, but ...19902372005
[preventive influenza vaccination]. 19902378120
evolutionary changes in influenza b are not primarily governed by antibody selection.influenza b viruses evolve more slowly than human influenza a, but no reasons for the difference have been established. we have analyzed sequence changes in the hemagglutinin and neuraminidase of influenza b viruses (and have determined four hemagglutinin sequences, of b/bonn/43, b/ussr/100/83, b/victoria/3/85, and b/memphis/6/86) in relation to antigenic properties and compared these with similar analyses of variation in influenza a antigens. independent of the slower rate of change in influenz ...19902378639
[effects of remantadine on fusion of lipid membranes of influenza a virus with plasma and internal membranes of lymphoblastic cells].the method of fluorescence dequenching was used to study the interaction between influenza virus a/krasnodar/101/59 and namalwa and raji lymphoblastoid cells. experiments with endocytosis inhibitors and fluorescence quenchers have shown that at ph = 5.0 the virus lipid envelopes are fused with the plasma membranes of the cells, and at ph = 7.4 the virus lipid envelopes are fused with the internal, presumably endosomal, membranes of the cells. remantadine at a concentration of 50-1000 micrograms/ ...19902378964
rapid focus reduction neutralization test of influenza a and b viruses in microtiter system.a rapid neutralization test for influenza a and b viruses was developed. in this method, a 96-well tissue culture plate was used for the preparation of cell monolayers and the peroxidase-antiperoxidase staining technique was used for the visualization of foci infected with these viruses. in the presence of trypsin and tragacanth gum, clear foci developed 1 day after infection. a linear relationship between virus dilutions and numbers of foci was observed. when neutralizing antibodies in some tes ...19902380359
acip releases 1990-1991 influenza vaccination recommendations. 19902382604
[the use of t-activin for the prevention of congenital influenzal infection in mice and the correction of the immune deficiency].viremia accompanying influenza infection and the possibility of transplacental passage of the virus into the fetus make it expedient to develop measures for the prophylaxis of intrauterine infection of the fetus in case of influenza during pregnancy. the work presents the optimum scheme of administration of t-activin for prophylactic purposes to pregnant mice with acute influenza infection. besides, the use of t-activin for immunocorrection in case of established congenital influenza infection i ...19902385991
vaccinia virus expression and sequence of an avian influenza nucleoprotein gene: potential use in diagnosis.the nucleoprotein (np) gene from avian influenza strain a/shearwater/aust/1/72 (h6n5) was cloned, sequenced, and expressed in vaccinia virus for the production of potent sera in immunised rabbits. the np gene is 1565 bp and shares greater than 95% amino acid sequence identity with other nps of the avian subtype. the recombinant np expressed by vaccinia virus comigrated with endogenous a/shearwater/aust/1/72 np by western blot analysis. polyclonal rabbit sera raised against recombinant np was eva ...19902386434
influenza. 19902386691
recommended composition of influenza virus vaccines for use in the 1990-1991 season. 19902386721
an endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class ii-restricted t cells.the recognition of virus-infected cells by class i mhc-restricted cytotoxic t cells requires endogenous processing of antigen for presentation. it is still unclear whether endogenous processing of antigen can be utilized by class ii mhc molecules for presentation. to test this possibility, a human b cell line expressing hla-a2 and hla-dr1 was infected with a recombinant vaccinia virus expressing the influenza a virus m1 matrix protein (vac-m1) and was assayed for lysis by different m1-specific c ...19902388037
genome and antigenic analysis of influenza a (h3n2) viruses isolated from an epidemic in a closed community of carmelite nuns.eighteen influenza a (h3n2) viruses were isolated during a single outbreak in a closed community of carmelite nuns. serological analysis of the virus haemagglutinin (has), using a panel of monoclonal antibodies, demonstrated antigenic microheterogeneity. in contrast, no significant biochemical differences were detected in viral genes by rna:rna hybridisation or in structural or nonstructural polypeptides analysed by high-resolution polyacrylamide gel electrophoresis (page) or by limited proteoly ...19902388044
[standardization of conditions for detecting the internal proteins of the influenza virus in studying their antigenic properties in solid-phase immunoenzyme analysis].the influence of the conditions of adsorption and virion destruction by freezing-thawing and detergents on the detection of m1 and np proteins of different influenza virus strains by solid-phase enzyme immunoassay with direct virion adsorption on polystyrene was studied. it was found that for the detection of m1 protein the optimal conditions included virion disruption with detergent and adsorption to polystyrene at 4 degrees c, and for np protein disruption by freezing-thawing at adsorption to ...19902389561
[the role of maternal virus-specific cytotoxic t-lymphocytes in the immunopathology of congenital influenza infection in mice].using 51cr isotope label it was demonstrated that a very low per cent of syngeneic lymphocytes derived from healthy donors and inoculated in the blood stream of uninfected or influenza virus-infected pregnant mice is found in fetuses before delivery. similar results were obtained after inoculation of virus-specific cytotoxic lymphocytes (ctl) into uninfected pregnant mice. after inoculation into the blood stream of infected pregnant mice of virus-specific ctl their migration into fetuses before ...19902389562
[characteristics of immune reactions to the influenza virus in mice with a slow influenzal infection].it had previously been shown that intrauterine infection of mice with influenza virus resulted in growth retardation and significant immunosuppression to various nonspecific agents and influenza virus. the present study demonstrated that such mice also had lower production of specific antibody and reduced capacity to form the delayed hypersensitivity to influenza virus. despite the lack of specific immune response, such mice had high levels of response to influenza virus in adoptive transfer. th ...19902389563
[the trypsin cleavage of hemagglutinin enhances the infectivity of the influenza virus in mice].mouse-pathogenic influenza a/aichi 2/68 (h3n2) grown in cell culture and having uncleaved hemagglutinin ha after treatment with trypsin underwent proteolytic shearing of ha (m.w. 75 kd) into two fragments: nal (60 kd) and ha2 (15 kd); its lethal effect on mice inoculated intranasally increased more than 200-fold. the virus treated with chemotrypsin underwent similar shearing of ha into hal and ha2; however, its lethal effect on mice was weak, analogous to that of intact virus with uncleaved ha.19902389564
[the use of immunoenzyme analysis in studying the etiologic structure of influenza morbidity in 1985-1988].in the periods of epidemic increases in the incidence of influenza in 1985-1988, approximately 600 patients with clinical diagnoses of arvi and influenza were examined for the presence of viral antigen in nasopharyngeal washings by solid-phase enzyme-immunoassay and for antibody rises in paired blood sera. the use of modified speia and original test sera for influenza type a and b viruses in rapid diagnosis of influenza made it possible to decode the etiology of the epidemic situations in 1985-1 ...19902389565
[stabilization of suspensions of the influenza virus using human serum albumin]. 19902389572
tumor necrosis factor-alpha production of influenza a virus-infected macrophages and potentiating effect of lipopolysaccharides.influenza a virus infections are commonly associated with symptoms that suggest involvement of tnf-alpha. in this study, we exposed human monocytes, rat alveolar macrophages, and murine pu5-1.8 macrophages to influenza a virus, strain puerto rico 8. we observed a productive infection that was accompanied by tnf-alpha mrna accumulation, tnf-alpha release and subsequent cell death. tnf-alpha production was dependent on exposure to live virus, in contrast to ifn release that was also induced by uv- ...19902391423
mechanism of influenza virus transcription inhibition by matrix (m1) protein.the mechanism by which influenza virus matrix (m1) protein inhibits viral rna (vrna) transcription was investigated. evidence has been generated that m1 protein inhibits the steps of vrna transcription initiation and reinitiation more effectively than that of rna chain elongation. the vrna-associated nucleocapsid protein (np) appears to be critical for this inhibition, implying that m1 protein binds to the ribonucleoprotein complex (rnp) through np.19902392615
the synthesis of influenza virus negative-strand rna takes place in insoluble complexes present in the nuclear matrix fraction.the replication of influenza virus rna in vitro has been studied by cell fractionation of mdck-infected cells and characterization of in vitro synthesized rna. analysis of the rna product polarity by liquid hybridization to excess single-stranded dna probes shows that only the rnp complexes present in the nuclear matrix fraction are able to synthesize negative-polarity rna. this rna product has been characterized as authentic vrna by size analysis, rnase-protection by unlabelled, positive-polari ...19902392881
inhibition of influenza virus sialidase and anti-influenza virus activity by plant flavonoids.flavonoids (103 species) were tested for inhibitory activity against influenza virus sialidase using sodium p-nitrophenyl-n-acetyl-alpha-d-neuraminate as substrate. 5,7,4'-trihydroxy-8-methoxyflavone from the root of scutellaria baicalensis showed the most potent activity (ic50, 55 microm), and this flavone appeared to be a non-competitive inhibitor of the enzyme. whereas, negligible or weak inhibitory activities were observed for mouse liver sialidase, beta-galactosidase and alpha-mannosidase a ...19902393958
antigenic properties and protective capacity of a cyclic peptide corresponding to site a of influenza virus haemagglutinin.two cyclic peptide analogues corresponding to residues 139-146 (site a) of influenza a virus haemagglutinin (strain x31) were synthesized. the ability of these peptides to react with anti-influenza virus antibodies was found to depend on the conformation of the loop and on the orientation in which the peptide was presented to antibodies. antibodies raised to the peptides were able to bind in elisa with influenza virus antigen that had been allowed to dry on the microtitre plate. when of1 mice we ...19902396470
[the pathomorphological changes in the brain and internal organs in experimental influenza infection in mice].the possibility of long persistence of influenza virus a in the brain and other organs of mice was established on the basis of complex virological, histological and electron microscopic studies. it was shown that the perivascular oedema of choroid plexus reaches the maximum during late stages of infection, after the clinical recovery. sharp increase of the permeability of cerebral vessels causing the perivascular oedema, especially in choroid plexus of lateral brain ventricles, proposed to be on ...19902396919
evolution of influenza a virus pb2 genes: implications for evolution of the ribonucleoprotein complex and origin of human influenza a virus.phylogenetic analysis of 20 influenza a virus pb2 genes showed that pb2 genes have evolved into the following four major lineages: (i) equine/prague/56 (eqpr56); (ii and iii) two distinct avian pb2 lineages, one containing fpv/34 and h13 gull virus strains and the other containing north american avian and recent equine strains; and (iv) human virus strains joined with classic swine virus strains (i.e., h1n1 swine virus strains related to swine/iowa/15/30). the human virus lineage showed the grea ...19902398532
comparative long-term effects in a mouse model system of influenza whole virus and purified neuraminidase vaccines followed by sequential infections.a comparison of inactivated whole influenza virus vaccine and purified influenza neuraminidase (na) in balb/c mice repeatedly challenged by homologous or heterologous h3n2 variant infections demonstrated an initial superiority of whole virus vaccine but the ultimate superiority of na vaccine in immunization after one or two boosting infections. parenteral administration of either vaccine followed by infection was much more effective than infection alone in the induction of either homologous or h ...19902401790
enhancement of anti-influenza cytotoxic t-lymphocyte activity in senescent mice by vaccination early in life.the elderly suffer significantly from influenza and respond poorly to influenza vaccines. this may be due to the fact that cytotoxic t-lymphocyte (ctl) activity is responsible for recovery from viral infections and is decreased in the elderly. we hypothesized that vaccination early in life might increase activity in senescence. to test this, groups of balb/c mice were infected with influenza virus and/or vaccinated with an inactivated vaccine. ctl activity was measured by 51cr release from h1n1- ...19902402165
influenza a virus and the neutrophil: a model of natural immunity.natural immune reactions are mediated by lymphocytes, macrophages/monocytes, and neutrophils. the latter have been implicated in a variety of self-surveillance models, i.e., activity against malignant host cells, participation in wound repair, and infliction of damage in postischemic perfusion injury. better characterized are the interactions with unopsonized pathogens through lectinophagocytosis mechanisms, where the lectin resides either on the phagocyte or on the microorganism. this review ex ...19902406357
now and future influenza vaccines.influenza is a modern day plague. in the young, the clinical picture is classical, but in the elderly, the disease may go unsuspected until complications such as pneumonia develop. influenza a and b viruses are responsible, and these viruses mutate with great regularity. antibodies to the ha and na surface antigens of influenza viruses, both naturally and vaccine induced, are protective. the earliest influenza vaccines were crude, toxic, and ineffective. with modern purification techniques, the ...19902407775
stimulated human alveolar macrophages secrete interferon.alveolar macrophages were isolated by bronchoalveolar lavage from normal subjects to determine whether these cells can be activated to produce interferon. macrophages were incubated for 24 h, and the supernatants were assayed for interferon using a plaque reduction assay (vesicular stomatitis virus and human amnion cells). the macrophages did not spontaneously release detectable amounts of interferon, but macrophages stimulated with either mitogens or classic inducers did release antiviral activ ...19852408524
a synthetic decapeptide of influenza virus hemagglutinin elicits helper t cells with the same fine recognition specificities as occur in response to whole virus.the immunogenicity of an isolated murine helper t cell determinant was studied. mice were immunized with a synthetic peptide corresponding to amino acid residues 111-120 of the influenza pr8 hemagglutinin (ha) heavy chain, a region previously identified as a major target of the helper t cell response to the ha molecule in virus-primed balb/c mice. lymph node t cells from these mice were fused with bw 5147 cells to produce t hybrids for clonal analysis of their recognition specificities. three t ...19852409149
expression of specific cytolytic activity by h-2i region-restricted, influenza virus-specific t lymphocyte clones.among murine class ii major histocompatibility complex (mhc)-restricted cytotoxic t lymphocyte (ctl) clones specific for type a influenza virus, we have identified both noncytolytic clones and clones exhibiting h-2 i region-restricted cytolytic activity. after appropriate antigenic stimulation, both cytolytic and noncytolytic clones proliferated in the absence of exogenous interleukin 2. all of the clones possess the thy-1.2+, lyt-1+2-, l3t4+ phenotype. the class ii mhc restriction of viral reco ...19852409206
hybridoma antibodies produced against bromelain derived cores of influenza virus.splenic lymphocytes from balb/c mice immunized with "cores" of influenza virus, obtained after bromelain cleavage of the surface glycoprotein, were fused with the p3-ns1/1-ag-1 mouse cell line to yield hybridoma cultures. among 20 stable cloned hybrid cells secreting monoclonal antibodies, one was specific for the nucleoprotein (np), 11 were specific for the membrane (m) protein and eight were specific for the hemagglutinin (ha). these "cores" used as immunogen contained only the internal protei ...19852409434
sequence homology between certain viral proteins and proteins related to encephalomyelitis and neuritis.post-infectious or post-vaccinal demyelinating encephalomyelitis and neuritis may be due to immunological cross-reactions evoked by specific viral antigenic determinants (epitopes) that are homologous to regions in the target myelins of the central and peripheral nervous systems. such homologies have been found by computer searches in which decapeptides in two human myelin proteins were compared with proteins of viruses known to infect humans. these viruses include measles, epstein-barr, influen ...19852409602
antigenic determinants of influenza virus hemagglutinin. xi. conformational changes detected by monoclonal antibodies.at ph 5 influenza virus hemagglutinin undergoes an irreversible conformational change (j.j. skehel, p. m. bayley, e. b. brown, s. r. martin, m. d. waterfield, j. m. white, i. a. wilson, and d. c. wiley (1982). proc. natl. acad. sci. usa 79, 968-972) which parallels the appearance of fusion activity of this molecule. this paper describes experiments which explore the conformational change using a panel of monoclonal antibodies which define four of the major antigenic sites of this protein. the re ...19852409671
the use of monoclonal antibodies for the antigenic analysis of influenza a viruses.monoclonal antibodies have been found to provide useful additional information for the antigenic analysis of influenza a viruses of the h3n2 and h1n1 subtypes. they have been particularly useful in the interpandemic period when multiple variants circulate concurrently.apparently heterogeneous isolates can be placed in fairly clear-cut groups on the basis of their reactivity with certain monoclonal antibody preparations. it is thought likely that variants reacting with the least number of monoclo ...19852410156
antigenic and amino acid sequence analyses of influenza viruses of the h1n1 subtype isolated between 1982 and 1984.since the reintroduction of influenza viruses of the h1n1 subtype into the human population in 1977, antigenically distinguishable viruses have been isolated each year from outbreaks of respiratory disease in young people. in this paper the antigenic properties of viruses representative of isolates made in 1982, 1983, and 1984 are compared, and the amino acid sequences of their haemagglutinins are presented. the results provide a complete description of the 1982 and 1983 h1n1 influenza virus hae ...19852410157
in vitro synthesis of full-length influenza virus complementary rna.influenza virus-specific rna has been synthesized in vitro, using cytoplasmic or microsomal fractions of influenza virus-infected mdck cells. the rna polymerase activity was stimulated 5-30 times by priming with apg. about 20-30% of the product was polyadenylated. most of the in vitro product was of positive polarity, as shown by hybridization to strand specific probes and by t1 fingerprinting of the poly(a)+ and poly(a)- rna segments encoding haemagglutinin and nucleoprotein. the size of poly(a ...19852410253
myxovirus replication in chicken embryos can be suppressed by aprotinin due to the blockage of viral glycoprotein cleavage.injection of the protease inhibitor, aprotinin, into the allantoic cavity of embryonated eggs infected at low m.o.i. with different influenza viruses and paramyxoviruses markedly reduced multiplication by at least 100-fold. under these conditions, most viral particles produced were non-infectious and contained uncleaved glycoproteins, presumably resulting from aprotinin suppression of protease activity.19852410557
a mutant of fowl plague virus (influenza a) with an enhanced electrophoretic mobility of rna segment 8.a temperature-sensitive mutant (ts 1/9) obtained by undiluted passage of fowl plague virus (fpv) at 33 degrees c carried a strong ts defect in rna segment 6 [neuraminidase (na) gene] and a weak ts defect in rna segment 8 [non-structural (ns) protein although the viral proteins have normal migration rates, the ns gene migrated during polyacrylamide gel electrophoresis (page) significantly faster than the ns gene of wild-type fpv, even after denaturation by glyoxal. despite this observation, the n ...19852410558
antigenic determinants of influenza virus haemagglutinin. x. a comparison of the physical and antigenic properties of monomeric and trimeric forms.haemagglutinin prepared from influenza virus a/memphis/1/71 by bromelain digestion was centrifuged through continuous sucrose gradients buffered at ph 7.4 or ph 4.9. from these gradients were isolated two forms of the protein which displayed different equilibrium sedimentation properties. one species behaved as a molecule with a mol. wt. of 190 000, the other with a mol. wt. of 70 000. these results are consistent with the separation of trimeric and monomeric haemagglutinin. a comparison of thei ...19852410559
monoclonal antibodies detect different forms of influenza virus hemagglutinin during viral penetration and biosynthesis.monoclonal antibodies specific for the influenza virus a/pr/8/34 hemagglutinin (ha) were used to examine the structure of the ha glycoprotein by immunofluorescence techniques during infection of mdck cells. one antibody (y8-10c2), shown previously to detect conformational alterations in the ha coinciding with the acid induction of viral fusion activity, bound to internalized virus but not to virus adsorbed to the cell surface. the binding of y8-10c2 was completely inhibited by ammonium chloride ...19852410628
location of antigenic sites on the three-dimensional structure of the influenza n2 virus neuraminidase.sequence analysis of the neuraminidase (na) genes of influenza virus x-7(f1) and of 12 variants selected with monoclonal antibodies has been used to define in physical terms the antigenic structure of this na, which was operationally established by r. g. webster, l. e. brown, and w. g. laver (1984, virology 135, 30-42). x-7(f1) is a reassortant virus containing the na of the early asian (h2n2) isolate a/ri/5+/57, and the results of antigenic and sequence analysis of x-7(f1) and of variants selec ...19852411049
is bivalent binding of monoclonal antibodies to different antigenic areas on the hemagglutinin of influenza virus required for neutralization of viral infectivity?biological activities of fab fragments of monoclonal igg antibodies to each of four nonoverlapping antigenic areas on the hemagglutinin molecule of a/seal/massachusetts/1/80 (h7n7) influenza virus were examined. fab fragments of the antibodies belonging to groups i and ii neutralized viral infectivity. these fab fragments inhibited hemagglutination of the virus and virus-induced hemolysis at ph 5.9. on the other hand, fab fragments of groups iii and iv antibodies showed neither neutralization no ...19852411245
cytotoxic t cells recognize fragments of the influenza nucleoprotein.recent work has shown that a major population of murine influenza a specific cytotoxic t lymphocytes (ctl) recognize the viral nucleoprotein. in order to investigate the mechanism by which this nonglycoprotein component of the virus is recognized by ctl, a series of deletion mutants of an a virus np gene were studied. the results showed that ctl recognize three distinct epitopes of the np molecule. both n- and c-terminal fragments of the protein are transported, independently of each other, to t ...19852411422
fine specificity analysis of human influenza-specific cloned cell lines.influenza-specific human-t-cell clones, proliferating in the presence of virus-infected cells with restriction by class ii molecules and displaying class ii-restricted ctl activity or specific helper activity in antibody synthesis, have been analyzed for antigenic specificities. all of them were obtained by in vitro stimulation against influenza a/texas virus. in all cases the virus specificity appeared identical in cytolytic and proliferative responses. three of the clones were broadly cross-re ...19852411429
immunoenzymatic staining of viral and chlamydial antigens in cell culture.methods are described for the conjugation of antibodies with biotin and for the use of these reagents in an immunoperoxidase staining procedure for infected cell cultures. this technique provides a simple, rapid, and specific approach to the identification and characterization of a number of viral and chlamydial isolates in the diagnostic laboratory.19852411466
homozygous typing cell-defined hla-dw specificities correlate better than serologically defined hla-dr specificities with restriction elements for influenza virus-specific proliferative human t lymphocyte clones.human t lymphocyte clones with specific proliferative response to influenza a virus were derived by limiting dilution from peripheral blood lymphocytes (pbl) after in vitro stimulation with autologous irradiated, virus-infected pbl. four okt3+4+8- t lymphocyte clones (tlc) that showed hla-restricted antigen-specific proliferative responses were used for a detailed analysis of the restriction elements for antigen presentation. none of the clones showed alloreactivity and all required the presence ...19852411701
recognition of viral antigens by human influenza a virus-specific t lymphocyte clones.the nature of the viral antigens recognized by influenza a virus-immune cytotoxic t lymphocytes (ctl) is still a matter of debate. we have used four human influenza a virus-specific t lymphocyte clones with antigen-specific cytotoxic and proliferative activity to investigate the requirements for recognition of viral antigens on infected cells. one clone recognized a cross-reactive determinant on the viral hemagglutinin, and two clones were specific for different epitopes on the viral nucleoprote ...19852411815
impaired measles virus-specific cytotoxic t cell responses in multiple sclerosis.to assess whether an virus-specific immune defect may be associated with multiple sclerosis (ms), we have examined the ability to generate measles virus-and influenza virus-specific cytotoxic t cells (ctl) in patients with ms, normal individuals, and other disease controls (odc). the mean (+/- sem) measles virus-specific ctl response for normal individuals and odc was 26.9 +/- 2.9% (n = 17) and 26.7 +/- 2.8% (n = 13) specific lysis, respectively. in contrast, the capacity of ms patients to gener ...19852411841
inhibition of influenza viral mrna synthesis in cells expressing the interferon-induced mx gene product.interferons alpha and beta induce an efficient antiviral state against influenza virus in mouse cells that possess the mx gene, but not in mouse cells that lack this gene. in mx-containing cells treated with interferon the amount of viral mrna synthesized as a result of primary transcription is drastically reduced. only two viral mrnas could be detected by northern analysis and by translating the poly(a)+ rna from infected cells in wheat germ extracts: a reduced amount of the mrna for nonstructu ...19852411949
influenza virus hemagglutinin-binding t cells in delayed hypersensitivity induced in mice.the ability of spleen t cells from mice inoculated with influenza virus to transfer delayed hypersensitivity increases after 5 days culture in the presence of tcgf and influenza virus or its hemagglutinin. enriched t cells have also a greater ability to bind viral hemagglutinin than cells which were not cultured and restimulated with either antigen. the results suggest the selection in vitro of specific antigen-binding t cells, able to transfer delayed hypersensitivity.19852412403
[synthesis of virus-specific rna in influenza virus-infected cells in the presence of bonafton]. 19852412888
stable expression of cytolytic activity by influenza virus-specific cytotoxic t lymphocytes.influenza-specific immune cytotoxic t lymphocyte (ctl) populations maintain a constant level of in vitro cytolytic activity. this is demonstrable with both heterogeneous populations of anti-viral ctl from immune donors and long-term ctl clones derived from primed ctl precursors. cytolytic machinery is stably expressed by these ctl populations under a variety of in vitro cultivation conditions. this finding is in contrast to results with alloreactive ctl generated by stimulation of primed ctl pre ...19852413123
[neuraminidase antigenic erythrocytic diagnostic agent in determining antibodies to the neuraminidase of influenza a viruses]. 19852413631
virion proteins and the perspectives of gene manipulations in vaccine preparation.the achievements and perspectives of genetic manipulations are described aiming at preparation of first generation subunit vaccines based on the synthesis in bacterial and eukaryotic cells of full-sized virion proteins expressing the main antigenic determinants. the preparation of such vaccines in bacterial cells seems out of perspective in the case of influenza, human hepatitis b, foot- and - mouth disease and some other viruses due to the peculiarities of structure and synthesis as well as low ...19852413750
epizootics of respiratory tract disease in swine in belgium due to h3n2 influenza virus and experimental reproduction of disease.in belgium, influenza virus was isolated from swine in 22 epizootics of respiratory tract disease in swine during 1984. in 8 of the epizootics, h3n2 influenza virus, related to the a/port chalmers/1/73 strain, was isolated. intratracheal inoculation of the isolates induced clinical signs. it was concluded that the a/port chalmers/1/73 strain was established in the belgian swine population and was responsible for the epizootics of respiratory tract disease in swine.19852413789
antigenic variation in the hemagglutinin-neuraminidase protein of human parainfluenza type 3 virus.sixteen monoclonal antibodies directed to the hemagglutinin-neuraminidase (hn) protein of a 1957 isolate of parainfluenza type 3 virus (piv3) were produced and used to examine antigenic variation in clinical strains. analysis of hemagglutination-inhibition reactivity patterns of antigenic variants selected in vitro in the presence of monoclonal antibodies indicated that there were a minimum of six distinct epitopes detectable on the hn molecule. competitive-binding assays indicated that these ep ...19852414910
the antigenic structure of the influenza b virus hemagglutinin: operational and topological mapping with monoclonal antibodies.we have probed the antigenic structure of the influenza b virus hemagglutinin (ha) with monoclonal antibodies specific for the ha of influenza b virus, b/oregon/5/80. seventeen laboratory-selected antigenic variants of this virus were analyzed by hemagglutination-inhibition (hi) assays or elisa and an operational antigenic map was constructed. in addition, the monoclonal antibodies were tested in a competitive binding assay to construct a topological map of the antigenic sites. in contrast to th ...19852414911
characterization of host cell binding variants of influenza virus by monoclonal antibodies.we have previously shown that a plaque-type mutant of influenza virus a/wsn has a growth advantage in mdbk cells because its hemagglutinin (ha) has a greater affinity for host cell receptors than does the ha of the parent virus. we show here that the mutant is also less sensitive than the parent to neutralization by antibodies to epitopes in at least two regions on the ha. wsn-specific monoclonal antibodies which had higher radioimmunoassay (ria) titers against the parent than the mutant virus a ...19852414912
the neuraminidases of the virulent and avirulent a/chicken/pennsylvania/83 (h5n2) influenza a viruses: sequence and antigenic analyses.to define the sequence changes that occurred in an avian influenza virus neuraminidase (na) during the evolution of virulence, we have studied the na of the virulent and avirulent a/chick/penn/83 (h5n2) influenza viruses. a comparison of the deduced amino acid sequence from these viruses shows that the virulent strain, which evolved from the avirulent by the accumulation of point mutations (bean et al., 1985), acquired four amino acid changes in the na: one in the transmembrane segment, one in t ...19852414922
[outlook on the use of interferon and its inducers in preventing influenza]. 19852414924
[detection of a heterogeneous population of influenza virus type a/h1n1 with monoreceptor sera to hemagglutinin antigenic determinants].studies of the antigenic composition of hemagglutinins of influenza h1n1 virus variants isolated in 1981 using monoreceptor antibody to individual antigenic determinants obtained by the selective adsorption method showed some variants to represent heterogeneous populations manifesting antigenic properties of different h1n1 viruses. passages of the heterogeneous virus in the presence of antiinfluenza serum resulted in cloning a subpopulation with the antigenic properties of the hemagglutinin simi ...19852414925
biological and immunological properties of haemagglutinin and neuraminidase expressed from cloned cdnas in prokaryotic and eukaryotic cells.to study the biological and immunological properties of influenza virus surface glycoproteins, cdna copies of the haemagglutinin (ha) and the neuraminidase (na) genes of a/wsn/33 influenza virus were cloned and expressed in prokaryotic and eukaryotic cells. in escherichia coli, maximum expression of ha is obtained only as a fusion protein in which the nh2-terminal portion is provided by a bacterial protein (i.e. beta gal or trple'). the ha expressed in bacteria (bacterial ha) is recognized by po ...19852414936
expression of haemagglutinin gene.antigenic drift of the haemagglutinin (ha) molecule of type a influenza viruses has been thought to occur by the accumulation of a series of point mutations in the antigenically important regions of the molecule. in order to study the antigenic sites on the ha molecule, an attempt was made to use the site-specific mutagenesis method.19852414937
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