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rescue of an influenza a virus wild-type pb2 gene and a mutant derivative bearing a site-specific temperature-sensitive and attenuating mutation.live attenuated influenza a virus vaccines are currently produced by the transfer of attenuating genes from a donor virus to new epidemic variants of influenza a virus, with the selection of reassortant viruses that possess the protective antigens (i.e., the two surface glycoproteins) of the epidemic virus and the attenuating genes from the donor virus. the previously studied attenuated donor viruses were produced by conventional methods such as passage of virus at low temperature or chemical mu ...19938230444
function of the mouse mx1 protein is inhibited by overexpression of the pb2 protein of influenza virus.the interferon-induced murine mx1 protein possesses an intrinsic antiviral activity with selectivity for influenza viruses. mx1 accumulates in the nucleus and inhibits the replication of influenza virus at the level of primary transcription. simultaneous overexpression of the three influenza virus polymerase subunits via recombinant vaccinia virus vectors can titrate out the inhibitory action of mx1 as determined by the amplification of a transfected recombinant viral reporter gene. a low degree ...19938249287
new antiviral antibiotics, kistamicins a and b. i. taxonomy, production, isolation, physico-chemical properties and biological activities.a new strain of microtetraspora parvosata subsp. kistnae subsp. nov. (atcc 55076) was found to produce new antiviral antibiotics, designated kistamicins a and b. these antibiotics exhibited activity against influenza virus type a and moderate activity against gram-positive bacteria.19938294237
sensitivity of nci-h292 human lung mucoepidermoid cells for respiratory and other human viruses.nci-h292 mucoepidermoid carcinoma cells from human lungs were shown in an earlier report to be a fully adequate substitute for primary rhesus monkey kidney (mk) cells for the isolation and propagation of the human paramyxoviruses. although sensitivity for ortho- and paramyxoviruses was the principal reason for using mk cells, the cells were also sensitive to many other viruses, which constituted another important value of mk cells. that mk cells supported the initial isolation and growth of so m ...19938314992
new developments in the diagnosis of viral diseases.major technical advances have occurred, especially in the last 5 years, in the laboratory diagnosis of viral infections. immunologic detection of immediate early antigens in specimens such as bronchoalveolar lavage fluid and blood inoculated into shell vial cell cultures, particularly for herpesvirus (cytomegalovirus, herpes simplex virus, varicella-zoster virus), has provided results 16 to 48 hours after inoculation rather than the several days required for recognition of cytopathic effects in ...19938345165
oral immunization with influenza virus in biodegradable microspheres.polymeric microspheres were evaluated as an oral antigen delivery system for immunization with influenza virus. the immune responses obtained were compared after either oral or systemic immunization of balb/c mice using purified, formalin-inactivated influenza virus type a/h3n2, either encapsulated in biodegradable and biocompatible microspheres or free in solution. the immunogenicity of formalin-treated influenza vaccine was preserved during the microencapsulation process, and the microencapsul ...19938418185
pradimicin s, a new pradimicin analog. i. taxonomy, fermentation and biological activities.a directed search for antibiotics active in a syncytium formation inhibition assay using a co-culture of hela-t4 cells expressing cd4 antigen and bsc-1 cells expressing gp-120 led to the isolation of pradimicin s, a new member of the pradimicin family. the producing strain (aa0851) was characterized as a new species of actinomadura for which the name actinomadura spinosa sp. nov. is proposed. production of pradimicin s by strain aa0851 was significantly improved by addition of ferrous sulfate (0 ...19938501000
viral pathogens of acute lower respiratory infections in pre-school nigerian children and clinical implications of multiple microbial identifications.in a prospective study of acute lower respiratory infections (alri), at the university college hospital, uch, ibadan, 35 viral pathogens were identified by immunofluorescence (if) techniques from 24 (68.6%) respiratory specimens from 35 hospitalised pre-school children. the respiratory diagnoses comprised croup, bronchiolitis, pneumonia and pleural effusion. the viral identifications comprised 14 (40.0%) of parainfluenza virus type 3, 10 (28.6%) of respiratory syncytial virus (rsv), 5 (14.3%) of ...19938512876
epitope mapping of cross-reactive monoclonal antibodies specific for the influenza a virus pa and pb2 polypeptides.characterization of the epitopes recognized by 21 monoclonal antibodies (mabs) specific for the influenza a virus pa (13 mabs) and pb2 (8 mabs) polypeptides (bárcena et al. (1994) j. virol. 68, 6900-6909) raised against denatured polypeptides produced in e. coli is described. mabs were characterized by: (1) competitive binding elisas; (2) mapping of the protein regions that specify their binding sites; and (3) analyses of their ability to recognize the corresponding viral protein in a number of ...19958533465
mutational analysis identifies functional domains in the influenza a virus pb2 polymerase subunit.a collection of influenza virus pb2 mutant genes was prepared, including n-terminal deletions, c-terminal deletions, and single-amino-acid insertions. these mutant genes, driven by a t7 promoter, were expressed by transfection into cos-1 cells infected with a vaccinia virus encoding t7 rna polymerase. mutant proteins accumulated to levels similar to that of wild-type pb2. immunofluorescence analyses showed that the c-terminal region of the protein is essential for nuclear transport and that inte ...19968627688
influenza virus pb1 protein is the minimal and essential subunit of rna polymerase.rna polymerase of influenza virus with the subunit structure pb1-pb2-pa is involved in both transcription and replication of the genome rna. the rna polymerase with transcription activity was reconstituted from three p proteins, which were separately isolated from insect cells infected with recombinant baculoviruses, each carrying cdna for one p protein. nuclear extracts of the insect cells infected with each of the recombinant baculoviruses or various combinations of these viruses were examined ...19968645093
[influenza virus infections in taiwan from 1979 to 1994].in order to understand the epidemic trends of influenza virus infection in taiwan, 5,677 throat-swab specimens were collected from june 1979 to december 1994. the influenza virus was detected in 300 specimens including samples collected at taichung and tainan from 1981 to 1982. among them, 209 isolates (67.9%) were identified as influenza virus type a and 99 isolates (32.1%) were type b influenza virus. influenza virus infection can be identified, based on the frequency of detection of the virus ...19958672941
isolation of influenzavirus a and b in plc/prf/5 cells.virus isolation was attempted in plc/prf/5 cells, a continuous primary liver carcinoma line, and secondary rhesus monkey kidney (2 degrees rhmk) cells from 19 clinical samples from which influenza a (n = 4) and b (n = 15) had been isolated previously. virus growth was determined by haemadsorption and immunofluorescence. influenza a was recovered in both cell types from all four samples tested. influenza b was re-isolated in both cell types from eight specimens, in plc/prf/5 only from two, and in ...19968757684
influenza virus polymerase basic protein 1 interacts with influenza virus polymerase basic protein 2 at multiple sites.three polymerase proteins of influenza type a virus interact with each other to form the active polymerase complex. polymerase basic protein 1 (pb1) can interact with pb2 in the presence or absence of polymerase acidic protein. in this study, we investigated the domains of pb1 involved in complex formation with pb2 in vivo, using coexpression and coimmunoprecipitation of the pb1-pb2 complex with monospecific antibodies. results show that pb1 possesses at least two regions which can interact inde ...19968794308
recombinant-baculovirus-expressed pb2 subunit of the influenza a virus rna polymerase binds cap groups as an isolated subunit.the influenza a virus rna-dependent rna polymerase catalyzes several reactions in transcription and replication of the genome rna. the first step in viral mrna synthesis is the recognition of the 5' end cap structure of host cell hnrna and the cleavage of the rna substrate between 10 and 14 nucleotides from the 5' end to generate capped primers for initiation of transcription of virus-specific mrnas. this report describes the use of an in vitro uv crosslinking and protein renaturation assay to i ...19968806170
molecular assembly of the influenza virus rna polymerase: determination of the subunit-subunit contact sites.influenza virus rna polymerase with the subunit structure pb1-pb2-pa is involved in both transcription and replication of the rna genome. by transfection of various combinations of cdna encoding wild-type and serial deletion mutants of each p protein subunit and co-immunoprecipitation with subunit-specific antibodies, the subunit-subunit contact sites on all three of the p proteins were determined. results indicate that binary complexes are formed between pb1-pb2 and pb1-pa but not between pb2-p ...19968811014
molecular dissection of influenza virus rna polymerase: pb1 subunit alone is able to catalyze rna synthesis.influenza virus rna polymerase with the subunit structure pb1-pb2-pa is involved in both transcription and replication of the rna genome. enzyme reconstitution experiments indicated that all three p proteins are required for rna synthesis in vitro (kobayashi, et al. virus res 22, 235-245, 1992). nuclear extracts of hela cells infected with three kinds of the recombinant vaccinia virus, each carrying one of the three p protein cdnas, exhibited the activity of complete replication, that is, vrna-s ...19968879132
mutations in the hemagglutinin and matrix genes of a virulent influenza virus variant, a/fm/1/47-ma, control different stages in pathogenesis.the mouse adapted strain of influenza a/fm/1/47 virus, fm-ma, has increased virulence due to mutations in ha, m1 and at least one other, unmapped, genome segment. genetic reassortants that differ due to the ha or m1 mutations were used to define the role of these mutations in pathogenesis. pathological changes in lungs of infected mice were assessed by hematoxylin phloxine saffron (hps) staining, and viral infection was measured by fluorescent antibody staining of thin sections and flow cytometr ...19968879138
identification of two separate domains in the influenza virus pb1 protein involved in the interaction with the pb2 and pa subunits: a model for the viral rna polymerase structure.the domains of the pb1 subunit of the influenza virus polymerase involved in the interaction with the pb2 and pa subunits have been defined by mutational analysis of pb1 protein. the experimental approach included in vivo competition of the pb1 activity, two-hybrid interaction assays and in vitro binding to pb1-specific matrices. mutants of the pb1 gene including n-terminal, c-terminal and internal deletions and single amino acid insertions were constructed. they were unable to support polymeras ...19968948635
influenza virus infections in taiwan from 1979 to 1995.in order to understand the epidemic trends of influenza virus infection in taiwan, 5,882 throat-swab specimens were collected from june 1979 to june 1995. influenza virus was detected in 313 specimens including samples collected at taichung and tainan from 1981 to 1982. among them, 214 isolates (68.4%) were identified as influenza virus type a, and 99 (31.6%) as type b. in the course of the surveillance, the influenza virus strain a/taiwan 1/86 (h1n1), known as a world-wide reference strain, was ...19968950640
serological study of responses to selected pathogens causing respiratory tract infection in the institutionalized elderly.in a prospective 2-year study, serological responses to selected pathogens were analyzed in 224 episodes of fever attributable to respiratory tract infection (51.8%) or of unknown source (48.2%) in 131 residents of two long-term-care facilities. a serological response was identified in 45 episodes (20.1%): chlamydia pneumoniae (14 episodes), haemophilus influenzae type b (1), influenza virus type a (14), respiratory syncytial virus (rsv;2), parainfluenza virus type 3 (7), c. pneumoniae and h. in ...19968953065
the influenza a virus pb2 polymerase subunit is required for the replication of viral rna.the transcription and replication of influenza virus rna (vrna) were reconstituted in vivo. the experimental approach involved the transfection of plasmids encoding the viral subunits of the polymerase and the nucleoprotein into cells infected with a vaccinia virus recombinant virus expressing the t7 rna polymerase. as templates, one of two model rnas was transfected: vnsz or cnsz rna. the rnas were 240 nucleotides in length, contained the terminal sequences of the ns viral segment, and were of ...19978995663
[ribozyme cleaving the mrna for influenza virus type a polymerase gene]. 19969026732
segment-specific noncoding sequences of the influenza virus genome rna are involved in the specific competition between defective interfering rna and its progenitor rna segment at the virion assembly step.the generation of influenza a virus defective interfering (di) particles was studied by using an ns2 mutant which produces, in a single cycle of virus replication, a large amount of di particles lacking the pa polymerase gene. the decrease in pa gene replication has been shown to occur primarily at the crna synthesis step, with preferential amplification of pa di rna species present in a marginal amount in the virus stock. in addition, at the assembly step the pa di rnas were preferentially inco ...19979032347
genetically engineered live attenuated influenza a virus vaccine candidates.we have generated new influenza a virus live attenuated vaccine candidates by site-directed mutagenesis and reverse genetics. by mutating specific amino acids in the pb2 polymerase subunit, two temperature-sensitive (ts) attenuated viruses were obtained. both candidates have 38 degrees c shutoff temperatures in mdck cells, are attenuated in the respiratory tracts of mice and ferrets, and have very low reactogenicity in ferrets. infection of mice or ferrets with either mutant conferred significan ...19979060631
infectious agents in acute respiratory disease in horses in ontario.a study of acute respiratory disease in horses in ontario was undertaken to determine the identity of current causative infectious agents. a nasopharyngeal swab was designed and utilized to maximize isolation of viruses, mycoplasma, and pathogenic bacteria. serum samples were collected for parallel determination of antibody titers to equine influenza virus type a subtype 1 (h7n7) and subtype 2 (h3n8), equine rhinovirus types 1 and 2, equine herpesvirus type 1, mycoplasma equirhinius, and mycopla ...19979087920
experimental infections with some pneumotropic viruses in the mouse. note i. virological and pathomorphological aspects of the associated infections with influenza virus, adenovirus and respiratory syncytial virus.in white mice, the associated infections with the influenza virus type a(h3n2), the adenovirus type 3 and the long strain of the respiratory syncytial virus, detected by the appearance of homologous serum antibodies and by positive i.f. reactions in pulmonary tissue, induce histological, histochemical and histo-enzymatic lesions, the severity of which exceeds that of the lesions in animals infected with only one of the mentioned viruses. in comparison with the morphological picture in animals in ...19959106398
evaluation of monoclonal antibodies for subtyping of currently circulating human type a influenza viruses.the hemagglutinin subtype specificities of six monoclonal antibodies (mabs) to influenza type a viruses were evaluated in a rapid culture assay by immunoperoxidase staining. confluent monolayers of mdck cells in multiwell plates were inoculated with (i) 23 reference viruses, (ii) 200 isolates collected during the influenza season 1995 to 1996, and (iii) 28 clinical specimens previously found to be influenza virus positive. after overnight incubation, the cells were fixed and stained with mabs iv ...19979114406
influenza among hospitalized adults with leukemia.influenza is one of the most important respiratory diseases of mankind, yet scant data exist concerning the frequency and clinical course of influenza in severely immunocompromised adults. from october 1993 to september 1994, we cultured the respiratory secretions of all adults with leukemia who were hospitalized with an acute respiratory illness at the university of texas m.d. anderson cancer center in houston. during a 9-week period from 29 november 1993 to 29 january 1994, influenza virus typ ...19979195063
two new lignans with activity against influenza virus from the medicinal plant rhinacanthus nasutus.two new lignans, rhinacanthin e (1) and rhinacanthin f (2), were isolated from the aerial parts of the plant rhinacanthus nasutus. their structures were established by detailed spectroscopic analysis. these compounds show significant antiviral activity against influenza virus type a.19979214738
immunodominance of a single ctl epitope in a primate species with limited mhc class i polymorphism.mhc class i molecules play a crucial role in immunity to viral infections by presenting viral peptides to cytotoxic t lymphocytes. one of the hallmarks of mhc class i genes in outbred populations is their extraordinary polymorphism, yet the significance of this diversity is poorly understood. certain species with reduced mhc class i diversity, such as the cotton-top tamarin (saguinus oedipus), are more susceptible to fatal viral infections. to explore the relationship between this primate's limi ...19979233634
the three subunits of the polymerase and the nucleoprotein of influenza b virus are the minimum set of viral proteins required for expression of a model rna template.the genes encoding the nucleoprotein, pb1, pb2, and pa proteins of the influenza virus strain b/panamá/45/90 have been cloned under control of the t7 rna polymerase promoter of plasmid pgem-3. transfection of the recombinant plasmids obtained into mammalian cells, which had been infected with a vaccinia virus encoding the t7 rna polymerase, resulted in expression of the expected influenza b virus polypeptides. moreover, it is shown that coexpression of the four recombinant core proteins in cos-1 ...19979281500
stimulation of antiviral activities of interferon by a liver extract preparation.the liver extract preparation adelavin9 (referred to as ext-fad hereinafter) is a combination product that consists of hog liver extract and flavin-adenine dinucleotide (fad). ext-fad has been reported to improve the histology of chronic liver injury and is widely used in japan. interferon (ifn) has been used to treat viral hepatitis. in this study, the action of ext-fad on the antiviral activity of ifn was examined using experimental models of viral infection in vitro and in vivo. ext-fad signi ...19979296286
an influenza a live attenuated reassortant virus possessing three temperature-sensitive mutations in the pb2 polymerase gene rapidly loses temperature sensitivity following replication in hamsters.the purpose of the present study was to produce an influenza a h2n2 donor virus from which an attenuating pb2 gene bearing three discrete temperature sensitive (ts) mutations could be readily transferred to currently epidemic influenza a h1n1 and h3n2 viruses via genetic reassortment. an influenza a transfectant virus was first produced that contained site-directed ts mutations at amino acids 112, 265, and 556 in the pb2 gene of influenza a/aa/60 virus origin in a background of the other seven r ...19979302747
use of oligonucleotide probes for selecting potential high-yielding influenza reassortants.a new method for rapid screening of high-yielding reassortants of influenza virus, as candidates for vaccine production, is described. oligonucleotide probes specific for all the parent genes of a/pr/8/34 (pr8), except the ha and the na were designed based on database information available for different influenza strains. digoxigenin labelled probes were tested by slot-blot hybridizations to purified rna from a panel of a/pr/8/34 wild type and a/pr/8/34 reassortant viruses. the results show that ...19979389403
dual respiratory virus infections.we retrospectively reviewed eight prospective epidemiological studies conducted between 1991 and 1995 for dual respiratory virus infection (drvi) to determine the frequency, associated comorbid conditions, clinical presentations, and morbidity related to drvi among immunocompetent persons. two viruses were identified as the cause of 67 (5.0%) of 1,341 acute respiratory virus infections. drvi was detected in patients from < 1 year to 79 years of age, in both sexes, and in many races. forty-two pe ...19979431390
etiology of acute childhood encephalitis at the hospital for sick children, toronto, 1994-1995.of 145 patients admitted to our hospital because of encephalitis-like illness, 50 patients hospitalized for > or =72 hours underwent standardized microbiological investigations. a confirmed or probable etiologic agent was identified in 20 cases (40%), including mycoplasma pneumoniae (9 cases). m. pneumoniae and enterovirus (2), herpes simplex virus (4), epstein-barr virus (1), human herpes-virus 6 (hhv-6) (1), hhv-6 and influenza virus type a (1), influenza virus type a (1), and powassan virus ( ...19989502462
low plasma levels of adrenocorticotropic hormone in patients with acute influenza.plasma levels of adrenocorticotropic hormone (acth) and cortisol were measured in young adults with influenza virus type a (h3n2) infection for whom cultures were positive and in comparable controls without symptoms or other evidence of illness. the mean plasma acth level +/- se in 19 patients with acute influenza was 13.5 +/- 2.1 pg/ml compared with 23 +/- 3.2 pg/ml in 11 controls (p = .02). mean plasma acth levels +/- se had risen to 21 +/- 4.1 pg/ml in specimens obtained from patients during ...19989524849
influenza virus nucleoprotein interacts with influenza virus polymerase proteins.influenza virus nucleoprotein (np) is a critical factor in the viral infectious cycle in switching influenza virus rna synthesis from transcription mode to replication mode. in this study, we investigated the interaction of np with the viral polymerase protein complex. using coimmunoprecipitation with monospecific or monoclonal antibodies, we observed that np interacted with the rnp-free polymerase protein complex in influenza virus-infected cells. in addition, coexpression of the components of ...19989621005
effective inhibition of influenza virus production in cultured cells by external guide sequences and ribonuclease p.the polymerase (pb2) and nucleocapsid (np) genes encoded by the genome of influenza virus are essential for replication of the virus. when synthetic genes that express rnas for external guide sequences targeted to the mrnas of the pb2 and np genes are stably incorporated into mouse cells in tissue culture, infection of these cells with influenza virus is nonproductive. endogenous rnase p cleaves the targeted influenza virus mrnas when they are in a complex with the external guide sequences. targ ...19989636148
rna-dependent activation of primer rna production by influenza virus polymerase: different regions of the same protein subunit constitute the two required rna-binding sites.the capped rna primers required for the initiation of influenza virus mrna synthesis are produced by the viral polymerase itself, which consists of three proteins pb1, pb2 and pa. production of primers is activated only when the 5'- and 3'-terminal sequences of virion rna (vrna) bind sequentially to the polymerase, indicating that vrna molecules function not only as templates for mrna synthesis but also as essential cofactors which activate catalytic functions. using thio u-substituted rna and u ...19989755184
simultaneous multiple viral infections in childhood acute lower respiratory tract infections in southern taiwan.thirty paediatric patients with acute lower respiratory tract infections (alri) caused by simultaneous multiple viral infections (smv) in a 3-year interval were reviewed. twenty patients were infected with two viruses simultaneously; nine patients with three viruses; and one patient with four viruses. the frequency of individual viruses were: adenovirus, 18 (60 per cent); respiratory syncytial virus, 7 (23 per cent); influenza virus type a, 6 (20 per cent); influenza virus type b, 15 (50 per cen ...19989819497
inhibition of influenza a virus replication by compounds interfering with the fusogenic function of the viral hemagglutinin.several compounds that specifically inhibited replication of the h1 and h2 subtypes of influenza virus type a were identified by screening a chemical library for antiviral activity. in single-cycle infections, the compounds inhibited virus-specific protein synthesis when added before or immediately after infection but were ineffective when added 30 min later, suggesting that an uncoating step was blocked. sequencing of hemagglutinin (ha) genes of several independent mutant viruses resistant to t ...19999847316
specific inhibition of influenza virus rna polymerase and nucleoprotein gene expression by liposomally encapsulated antisense phosphorothioate oligonucleotides in mdck cells.we have demonstrated that antisense phosphorothioate oligonucleotides (s-odns) inhibit influenza a virus replication in mdck cells. liposomally encapsulated and free antisense s-odns with four target sites (pb1, pb2, pa and np genes) were tested for their abilities to inhibit virus-induced cytopathogenic effects in a mtt assay using mdck cells. the liposomally encapsulated s-odn complementary to the site around the pb2 aug initiation codon showed highly inhibitory effects. in contrast, the inhib ...19989875404
antiviral activities of marine pseudomonas polysaccharides and their oversulfated derivatives.: a marine pseudomonas species wak-1 strain simultaneously produces extracellular glycosaminoglycan and sulfated polysaccharide. among the antiviral activities tested for these polysaccharides, the latter showed anti-hsv-1 activity in rpmi 8226 cells (50% effective concentration is 1.4 µg/ml). oversulfated derivatives of these polysaccharides prepared by dicyclohexylcarbodiimide-mediated reaction for both polysaccharides showed antiviral activities against influenza virus type a (for glycosamino ...199910373612
revelation of antiviral activities by artificial sulfation of a glycosaminoglycan from a marine pseudomonas.: sulfated derivatives of a glycosaminoglycan containing l-glutamic acid produced by a marine pseudomonas species, no. 42 strain, were prepared by the method of dicyclohexyl-carbodiimide-mediated reaction. both low and high degrees of sulfation of the polysaccharides (products a1 and a2, respectively) were investigated for their antiviral activities against influenza virus type a (fluv-a) and b (fluv-b) in mdck cells. both preparations showed antiviral activity against fluv-a at the 50% antivira ...199910373617
genetic analysis of mouse-adapted influenza a virus identifies roles for the na, pb1, and pb2 genes in virulence.adaptation of the prototype a/fm/1/47 h1n1 strain to mice resulted in selection of the a/fm/1/47-ma variant with increased virulence. earlier analysis identified mutations in the ha and m1 genes that increase virulence in the mouse. complete sequence analysis identified mutations in the pb1, pb2, ha, na, and m1 genes. reassortants were produced between the parental fm and fm-ma strains to obtain viruses that differ due to combinations of mutant genes. to assess the relationship between virulence ...199910426210
clinical characteristics of acute viral lower respiratory tract infections in hospitalized children in seoul, 1996-1998.this study was performed to investigate the etiologic agents, age distribution, clinical manifestations and seasonal occurrence of acute viral lower respiratory tract infections in children. we confirmed viral etiologies using nasopharyngeal aspirates in 237 patients of the ages of 15 years or younger who were hospitalized for acute lower respiratory tract infection (alri) from march 1996 to february 1998 at samsung seoul hospital, seoul, korea. the overall isolation rate was 22.1%. the viral pa ...199910485620
rhabdomyolysis and acute renal failure associated with influenza virus type a.two patients with rhabdomyolysis-induced acute renal failure due to influenza a virus infection are presented. both had influenza symptoms, with high fever and severe muscular pain leading to walking problems. in addition, they were dehydrated due to vomiting and diarrhoea. both had evidence of an ongoing influenza infection according to serological tests. muscle injury due to the viral infection gave rise to rhabdomyolysis with efflux of myoglobin from the muscles, causing renal failure. in con ...199910515090
two separate sequences of pb2 subunit constitute the rna cap-binding site of influenza virus rna polymerase.influenza virus rna polymerase with the subunit composition of pb1-pb2-pa is a unique multifunctional enzyme with the activities of both synthesis and cleavage of rna, and is involved in both transcription and replication of the rna genome. transcription is initiated by using capped rna fragments, which are generated after cleavage of host cell mrna by the rna polymerase-associated capped rna endonuclease. to identify the rna cap 1-binding site on the rna polymerase, viral ribonucleoprotein (rnp ...199910526235
acute lower respiratory infections in hospitalized children over a 6 year period in tokyo.acute lower respiratory infections are major causes of hospitalization in children and are mainly caused by respiratory viruses. in the present study, we investigated the etiologic agents responsible for acute lower respiratory infections from the period november 1986 to october 1992 in order to determine the seasonal pattern and different characteristics of age distribution of respiratory infectious agents, mainly virus infections.199910530065
[a case of non-herpetic acute encephalitis presenting high intensity lesion at unilateral temparal cortex on mr flair image].we reported a case of non-herpetic acute encephalitis with unilateral temporal cortex lesion revealed by mr imaging and spect study. the patient was an eighteen years old woman who developed tonic-clonic seizure after common cold symptom. she was healthy before this episode. neurological abnormality was only a single convulsion at onset and there was no other abnormal physical and neurological signs except for low grade fever. electroencephalogram showed spike and slow wave complex of 2 hz focus ...199910548915
comparative analysis of the ability of the polymerase complexes of influenza viruses type a, b and c to assemble into functional rnps that allow expression and replication of heterotypic model rna templates in vivo.influenza viruses type a, b, and c are human pathogens that share common structural and functional features, yet they do not form natural reassortants. to determine to what extent type-specific interactions of the polymerase complex with template rna contribute to this lack of genotypic mixing, we investigated whether homotypic or heterotypic polymerase complexes support the expression and replication of model type a, b, or c rna templates in vivo. a plasmid-based expression system, as initially ...199910600605
phylogenetic analysis of the three polymerase genes (pb1, pb2 and pa) of influenza b virus.phylogenetic patterns of the three polymerase (pb2, pb1 and pa) genes of a total of 20 influenza b viruses isolated during a 58 year period, 1940-1998, were analysed in detail in a parallel manner. all three polymerase genes consistently showed evolutionary divergence into two major distinct lineages and their amino acid profiles demonstrated conserved lineage-specific substitutions. dendrogram topologies of the pb2 and pb1 genes were very similar and contrasted with that of the pa gene. it was ...200010725418
expression of functional influenza virus rna polymerase in the methylotrophic yeast pichia pastoris.influenza virus rna polymerase with the subunit composition pb1-pb2-pa is a multifunctional enzyme with the activities of both synthesis and cleavage of rna and is involved in both transcription and replication of the viral genome. in order to produce large amounts of the functional viral rna polymerase sufficient for analysis of its structure-function relationships, the cdnas for rna segments 1, 2, and 3 of influenza virus a/pr/8, each under independent control of the alcohol oxidase gene promo ...200010756019
genetic analysis of the compatibility between polymerase proteins from human and avian strains of influenza a viruses.in order to determine how efficiently the polymerase proteins derived from human and avian influenza a viruses can interact with each other in the context of a mammalian cell, a genetic system that allows the in vivo reconstitution of active ribonucleoproteins was used. the ability to achieve replication of a viral-like reporter rna in cos-1 cells was examined with heterospecific mixtures of the core proteins (pb1, pb2, pa and np) from two strains of human viruses (a/puerto rico/8/34 and a/victo ...200010769071
evolutionary characterization of the six internal genes of h5n1 human influenza a virus.the entire nucleotide sequences of all six internal genes of six human h5n1 influenza a viruses isolated in hong kong in 1997 were analysed in detail from a phylogenetic point of view and compared with the evolutionary patterns of the haemagglutinin and neuraminidase genes. despite being isolated within a single year in the same geographical location, human h5n1 viruses were characterized by a variety of amino acid substitutions in the ribonucleoprotein complex [pb2, pb1, pa and nucleoprotein (n ...200010769072
the wilhelmine e. key 1999 invitational lecture. predicting the evolution of human influenza a.we studied the evolution of the ha1 domain of the h3 hemagglutinin gene from human influenza virus type a. the phylogeny of these genes showed a single dominant lineage persisting over time. we tested the hypothesis that the progenitors of this single evolutionarily successful lineage were viruses carrying mutations at codons at which prior mutations had helped the virus to avoid human immune surveillance. we found evidence that eighteen hemagglutinin codons appeared to have been under positive ...200010833042
contemporary analysis of mhc-related immunodominance hierarchies in the cd8+ t cell response to influenza a viruses.early studies of influenza virus-specific cd8+ t cell-mediated immunity indicated that the level of ctl activity associated with h2db is greatly diminished in mice that also express h2kk. such mhc-related immunodominance hierarchies are of some interest, as they could lead to variable outcomes for peptide-based vaccination protocols in human populations. the influence of h2kk on the h2db-restricted response profile has thus been looked at again using a contemporary, quantitative, ifn-gamma-based ...200010946264
inhibition of influenza virus replication in cultured cells by rna-cleaving dna enzyme.influenza virus replication has been effectively inhibited by antisense phosphothioate oligonucleotides targeting the aug initiation codon of pb2 mrna. we designed rna-cleaving dna enzymes from 10-23 catalytic motif to target pb2-aug initiation codon and measured their rna-cleaving activity in vitro. although the rna-cleaving activity was not optimal under physiological conditions, dna enzymes inhibited viral replication in cultured cells more effectively than antisense phosphothioate oligonucle ...200010996307
influenza a virus infection of human middle ear cells in vitro.human-derived normal middle ear mucosal cells can be harvested and cultured and will support influenza a virus (inf a) infection.200011037837
mapping of functional domains on the influenza a virus rna polymerase pb2 molecule using monoclonal antibodies.monoclonal antibodies against the pb2 of a/puerto rico/8/34 (a/pr/ 8/34) (h1n1) were prepared in order to define the functional domains of the rna polymerase of influenza virus. the fifteen monoclonal antibodies that were generated were divided into 4 groups on the basis of elisa binding to pb2 or its peptide fragments. six group i antibodies that bound to the pb2 n-terminal region (amino acids 1-104) did not inhibit transcription by the viral ribonucleoprotein complex. a single group ii antibod ...200011043953
neuraminidase inhibitors in the treatment of influenza a and b--overview and case reports.influenza viruses type a and b can cause a wide spectrum of illness, and they are responsible for considerable mortality and morbidity. with the new neuraminidase inhibitors, of which zanamivir was the first drug to be licensed, the physician has antivirals at his disposal which are safe and effective against both influenza virus type a and type b. available data from clinical phase iii studies indicate benefits in terms of a reduction in the median time to alleviation of major symptoms by 1.5 t ...200011073130
maximum likelihood estimation on large phylogenies and analysis of adaptive evolution in human influenza virus a.algorithmic details to obtain maximum likelihood estimates of parameters on a large phylogeny are discussed. on a large tree, an efficient approach is to optimize branch lengths one at a time while updating parameters in the substitution model simultaneously. codon substitution models that allow for variable nonsynonymous/synonymous rate ratios (omega = d(n)/d(s)) among sites are used to analyze a data set of human influenza virus type a hemagglutinin (ha) genes. the data set has 349 sequences. ...200011080365
[evaluation of influenza virus type a detection kit].we evaluated a new influenza virus type a detection kit (influa-ad "seiken") and compared it to virus isolation and rt-pcr using throat swab specimens. our results were as follows: 1) from 13 specimens in which influenza virus type a was isolated, influa-ad "seiken" detected 12 while rt-pcr detected 9. 2) from 7 specimens in which influenza virus type b was isolated, influa-ad "seiken" detected 0 while rt-pcr detected 1. 3) from 2 specimens in which adeno virus was isolated, influa-ad "seiken" d ...200011109767
spectrum of virus inhibition by consensus interferon ym643.the spectrum of viruses inhibited by a genetically engineered consensus interferon (ifn) ym643 (interferon alfacon-1) was evaluated using a cytopathic effect inhibition assay or plaque inhibition assay for five dna viruses and 12 rna viruses. this activity was compared to that of natural ifn-alpha derived from namalwa lymphoblastoid cell line [ifn-alpha (namalwa)]. the viruses inhibited by both ifns were herpesvirus types 1 and 2, human cytomegalovirus, varicella-zoster virus, vesicular stomatit ...200011142632
zanamivir. no noticeable progress against influenza.* zanamivir (relenza((r)), glaxo wellcome) an antiviral drug, is marketed for treatment of influenza during outbreaks.* the clinical file consists mainly of three doubleblind, placebo-controlled trials.* when administered to patients with symptoms of influenza, at an inhaled dose of 10 mg twice daily, zanamivir has no clear benefit, or very limited benefit (hastening clinical recovery by 0.7 to 1.5 days) provided treatment is started within 30 hours of symptom onset. zanamivir seems to act on in ...200011184246
diversity of epitope and cytokine profiles for primary and secondary influenza a virus-specific cd8+ t cell responses.screening with the flow cytometric ifn-gamma assay has led to the identification of a new immunogenic peptide (ssyrrpvgi) [corrected] from the influenza pb1 polymerase (pb1(703--711)) and a mimotope (isplmvaym) from the pb2 polymerase (pb2(198--206)). cd8(+) t cells specific for k(b)pb1(703) make both ifn-gamma and tnf-alpha following stimulation with both peptides. the cd8(+) k(b)pb1(703)(+) population kills pb2(198)-pulsed targets, but cell lines stimulated with pb2(198) neither bind the k(b)p ...200111254721
antisense therapy of influenza.the liposomally encapsulated and the free antisense phosphorothioate oligonucleotides (s-odns) with four target sites (pb1, pb2, pa, and np) were tested for their abilities to inhibit virus-induced cytopathogenic effects by a mtt assay using mdck cells. the liposomally encapsulated s-odn complementary to the sites of the pb2-aug initiation codon showed highly inhibitory effects. on the other hand, the inhibitory effect of the liposomally encapsulated s-odn targeted to pb1 was considerably decrea ...200111292569
the active sites of the influenza cap-dependent endonuclease are on different polymerase subunits.the cap-dependent endonuclease of the influenza viral rna polymerase, which produces the capped rna primers that initiate viral mrna synthesis, is comprised of two active sites, one for cap binding and one for endonuclease cleavage. we identify the amino acid sequences that constitute these two active sites and demonstrate that they are located on different polymerase subunits. binding of the 5' terminal sequence of virion rna (vrna) to the polymerase activates a tryptophan-rich, cap-binding seq ...200111296240
nucleotides at the extremities of the viral rna of influenza c virus are involved in type-specific interactions with the polymerase complex.influenza a and c viruses share common sequences in the terminal noncoding regions of the viral rna segments. differences at the 5'- and 3'-ends exist, however, that could contribute to the specificity with which the transcription/replication signals are recognized by the cognate polymerase complexes. previously, by making use of a transient expression system for the transcription and replication of a reporter rna template bearing either type a or type c extremities, it was shown that a type c r ...200111297682
residue 627 of pb2 is a determinant of cold sensitivity in rna replication of avian influenza viruses.human influenza a viruses replicate in the upper respiratory tract at a temperature of about 33 degrees c, whereas avian viruses replicate in the intestinal tract at a temperature close to 41 degrees c. in the present study, we analyzed the influence of low temperature (33 degrees c) on rna replication of avian and human viruses in cultured cells. the kinetics of replication of the np segment were similar at 33 and 37 degrees c for the human a/puerto-rico/8/34 and a/sydney/5/97 viruses, whereas ...200111333924
sequences in influenza a virus pb2 protein that determine productive infection for an avian influenza virus in mouse and human cell lines.reverse genetics was used to analyze the host range of two avian influenza viruses which differ in their ability to replicate in mouse and human cells in culture. engineered viruses carrying sequences encoding amino acids 362 to 581 of pb2 from a host range variant productively infect mouse and human cells.200111333926
hairpin loop structure in the 3' arm of the influenza a virus virion rna promoter is required for endonuclease activity.previous studies have shown that the 5' arm of the influenza a virus virion rna promoter requires a hairpin loop structure for efficient endonuclease activity of influenza virus rna polymerase, an activity that is required for the cap-snatching activity of primers from host pre-mrna. here we examine whether a hairpin loop is also required in the 3' arm of the viral rna promoter. we study point mutations at each nucleotide position (1 to 12) within the 3' arm of the promoter as well as complement ...200111435584
zanamivir: new preparation. no tangible progress against influenza.(1) zanamivir, an antiviral drug, is marketed in europe and the united states for treatment of influenza during outbreaks. (2) the clinical file mainly consists of three double-blind, placebo-controlled trials. (3) when administered to patients with symptoms of influenza, at an inhaled dose of 10 mg twice a day, zanamivir has no clear or at least limited benefit, hastening clinical recovery by 0.7-1.5 days, provided that treatment is started within 30 hours of symptom onset. zanamivir seems to ...200011503795
antigen-specific cd8(+) t cells persist in the upper respiratory tract following influenza virus infection.because little is known about lymphocyte responses in the nasal mucosa, lymphocyte accumulation in the nasal mucosa, nasal-associated lymphoid tissue (nalt), and cervical lymph nodes (cln) were determined after primary and heterosubtypic intranasal influenza challenge of mice. t cell accumulation peaked in the nasal mucosa on day 7, but peaked slightly earlier in the cln (day 5) and later (day 10) in the nalt. tetrameric staining of nasal mucosal cells revealed a peak accumulation of cd8 t cells ...200111544317
molecular basis for high virulence of hong kong h5n1 influenza a viruses.in 1997, an h5n1 influenza a virus was transmitted from birds to humans in hong kong, killing 6 of the 18 people infected. when mice were infected with the human isolates, two virulence groups became apparent. using reverse genetics, we showed that a mutation at position 627 in the pb2 protein influenced the outcome of infection in mice. moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.200111546875
a combination vaccine confers full protection against co-infections with influenza, herpes simplex and respiratory syncytial viruses.combined/composite vaccines should be useful in reducing the number of vaccinations and provide more flexibility in confronting biological warfare scenarios. we tested the effectiveness of a composite genetic vaccine designed from previously known protective antigens directed against influenza a virus (inf-a), herpes simplex virus type-1 (hsv-1) and respiratory syncytial virus (rsv) in a mouse-based challenge. immunizing mice with a pool of four plasmids; inf-a haemagglutinin (ha), inf-a nucleop ...200111672920
influenza virus types and subtypes detection by single step single tube multiplex reverse transcription-polymerase chain reaction (rt-pcr) and agarose gel electrophoresis.influenza virus type and subtype specific primers were selected for use in reverse transcription polymerase chain reaction (rt-pcr). the selected primer sets were used in a single step rt-pcr of influenza virus rna in multiplex format for the detection of virus type and subtypes. three one step reaction conditions are optimized: (1) multiplex typing only, (2) multiplex subtyping of influenza a, and (3) multiplex typing and subtyping simultaneously. rna from strains of influenza virus type a of s ...200211684304
independent and synergistic effects of interleukin-18 and interleukin-12 in augmenting cytotoxic t lymphocyte responses and ifn-gamma production in aging.aged mice exhibit diminished cd8(+) cytotoxic t lymphocyte (ctl) response to influenza virus. previously, interleukin-12 (il-12) was shown to partially restore in vitro influenza virus-specific cd8(+) ctl activity and interferon-gamma (ifn-gamma) production in aged mice. the present study investigated il-18 production and its ability to collaborate with il-12 to enhance these responses to the levels of young mice. il-18 protein production and mrna expression in influenza virus-specific ctl from ...200111710997
antigenic variation among isolates of infectious salmon anaemia virus correlates with genetic variation of the viral haemagglutinin gene.infectious salmon anaemia virus (isav), an orthomyxovirus-like virus, is an important fish pathogen in marine aquaculture. virus neutralization of 24 isav isolates in the to cell line using rabbit antisera to the whole virus and comparative sequence analysis of their haemagglutinin (ha) genes have allowed elaboration on the variation of isav isolates. the 24 viruses were neutralized to varying degrees, revealing two major antigenic groups, one american and one european. sequence analysis of the ...200111714961
effect of rapid diagnosis of influenza virus type a on the emergency department management of febrile infants and toddlers.evidence shows that the rapid detection of influenza using an enzyme-linked immunosorbent assay decreases antibiotic use in the treatment of pediatric patients. to our knowledge, the effect on other diagnostic testing in an emergency department (ed) has not been examined.200211772189
reverse genetics approach towards understanding pathogenesis of h5n1 hong kong influenza a virus infection.in 1990, palese and colleagues established a method (reverse genetics) that allowed one to generate influenza virus containing a gene segment derived from cloned cdna. although this method contributed tremendously to our understanding of influenza pathogenesis, the requirement of helper viruses limited its use in many experimental settings. recently, we and others established systems for the generation of influenza viruses entirely from cloned cdnas. these systems require only dna cloning and tr ...200111779382
definition of the minimal viral components required for the initiation of unprimed rna synthesis by influenza virus rna polymerase.the first 11 nt at the 5' end of influenza virus genomic rna were shown to be both necessary and sufficient for specific binding by the influenza virus polymerase. a novel in vitro transcription assay, in which the polymerase was bound to paramagnetic beads via a biotinylated 5'-vrna oligonucleotide, was used to study the activities of different forms of the polymerase. complexes composed of co-expressed pb1/pb2/pa proteins and a sub-complex composed of pb1/pa bound to the 5'-vrna oligonucleotid ...200211788704
complications associated with influenza infection. 200211807195
apoptosis in cultured human fetal membrane cells infected with influenza virus.we investigated the induction of apoptosis in cultured human fetal membrane cells infected with influenza virus type a. we found that influenza virus yield in supernatants of primary cultured chorion and amnion cells prepared from human fetal membranes increased 6 h after infection. chromosomal dna was fragmented into oligonucleosomes at 48 h after influenza virus infection in chorion cells but not in mock-infected chorion cells, mock-infected amnion cells or influenza virus-infected amnion cell ...200211824537
absence of sp-a modulates innate and adaptive defense responses to pulmonary influenza infection.mice lacking surfactant protein sp-a [sp-a(-/-)] and wild type sp-a(+/+) mice were infected with influenza a virus (iav) by intranasal instillation. decreased clearance of iav was observed in sp-a(-/-) mice and was associated with increased pulmonary inflammation. treatment of sp-a(-/-) mice with exogenous sp-a enhanced viral clearance and decreased lung inflammation. uptake of iav by alveolar macrophages was similar in sp-a(-/-) and sp-a(+/+) mice. myeloperoxidase activity was reduced in isolat ...200211839553
[outbreaks due to respiratory syncytial virus and influenzavirus a/h3n in institutionalized aged. role of immunological status to influenza vaccine and possible implication of caregivers in the transmission].report of epidemiological, clinical and virological data collected from the prospective surveillance of febrile episodes observed in aged residents of a long-stay care unit of 33 beds, at the university hospital of saint-etienne, during the 1997-1998 winter season.200211913077
genetic and antigenic analysis of the first a/new caledonia/20/99-like h1n1 influenza isolates reported in the americas.from february through may of 1999, 13 cases of influenza a virus (fluav), type h1n1 were reported at a department of defense influenza surveillance sentinel site in lima, peru. genetic and antigenic analysis by hemagglutination inhibition and direct nucleotide sequencing of the ha1 region of the hemagglutinin gene were performed on two isolates, a/peru/1641/99 and a/peru/1798/99. both isolates were distinct from the bayern/7/95-like viruses circulating in the americas and closely related to a be ...200211971776
evaluation of the directigen flua+b test for rapid diagnosis of influenza virus type a and b infections.directigen flua+b (bd diagnostic systems, sparks, md.), a new rapid test for the detection of influenza virus types a and b, was evaluated with nasopharyngeal aspirate specimens collected from 250 patients in comparison with culture and direct fluorescent antigen (dfa) detection tests. the patients studied were predominantly children, 80% being </=6 years old. specimens negative by culture but positive by the directigen flua+b or dfa tests were analyzed by reverse transcription-pcr to resolve th ...200211980941
fine mapping of the subunit binding sites of influenza virus rna polymerase.influenza virus rna polymerase consists of three subunits, pb1, pb2 and pa, and catalyzes both transcription and replication of the rna genome. pb1 is a catalytic subunit of rna polymerization and a core of the subunit assembly. the subunit binding sites were mapped at about several hundred amino-acid size. fine mapping of the subunit binding sites was determined. the pb1-pa binding regions were mapped within in the n-terminal 25 amino acids of pb1 and 668-692 of pa. pb1 and pb2 interacted withi ...200212008925
combination treatment of influenza a virus infections in cell culture and in mice with the cyclopentane neuraminidase inhibitor rwj-270201 and ribavirin.treatment of virus infections with compounds acting by different mechanisms may lead to more potent effects when these agents are used in combination. under this premise, two known active influenza virus inhibitors, ribavirin and the novel cyclopentane influenza virus neuraminidase inhibitor (1s,2s,3r,4r)-3-[(1s)-(acetylamino)-2-ethylbutyl]-4-[(aminoiminomethyl)amino]-2-hydroxy-cyclopentanecarboxylic acid (rwj-270201, bcx-1812) were studied. experiments in cell culture demonstrated that rwj-2702 ...200212011541
structural studies of the resistance of influenza virus neuramindase to inhibitors.zanamivir and oseltamivir, specific inhibitors of influenza virus neuraminidase, have significantly different characteristics in resistance studies. in both cases resistance is known to arise through mutations in either the hemagglutinin or neuraminidase surface proteins. a new inhibitor under development by biocryst pharmaceuticals, bcx-1812, has both a guanidino group, as in zanamivir, and a bulky hydrophobic group, as in oseltamivir. using influenza a/nws/tern/australia/g70c/75 (h1n9), neuram ...200212014958
accuracy and power of bayes prediction of amino acid sites under positive selection.bayes prediction quantifies uncertainty by assigning posterior probabilities. it was used to identify amino acids in a protein under recurrent diversifying selection indicated by higher nonsynonymous (d(n)) than synonymous (d(s)) substitution rates or by omega = d(n)/d(s) > 1. parameters were estimated by maximum likelihood under a codon substitution model that assumed several classes of sites with different omega ratios. the bayes theorem was used to calculate the posterior probabilities of eac ...200212032251
local surveillance of influenza in the united kingdom: from sentinel general practices to sentinel cities?surveillance of influenza in england and wales utilises a disparate geographical network of general practices to provide clinical data in the form of weekly consultation rates for influenza and 'influenza-like illness'. this network accurately detects and monitors seasonal influenza activity at national and supra-regional levels. localised regional and sub-regional epidemics are less easily detected. we describe a localised epidemic of influenza affecting a deprived urban community in the north ...200212070970
role of influenza a virus hemagglutinin in neurovirulence for mammalians.influenza viruses with potential neuroinvasiveness for humans emerged in hong kong in 1997. prophylactic and therapeutic strategies are urgently needed for controlling the central nervous system complications caused by influenza. here we review recent advances toward understanding of the possible mechanisms of the neuropathogenesis of influenza virus infection, especially focusing on the role of viral hemagglutinin glycoprotein.200212137193
dna vaccine expressing conserved influenza virus proteins protective against h5n1 challenge infection in mice.influenza vaccination practice, which is based on neutralizing antibodies, requires being able to predict which viral strains will be circulating. if an unexpected strain, as in the 1997 h5n1 hong kong outbreak, or even a pandemic emerges, appropriate vaccines may take too long to prepare. therefore, strategies based on conserved influenza antigens should be explored. we studied dna vaccination in mice with plasmids expressing conserved nucleoprotein (np) and matrix (m) from an h1n1 virus. after ...200212141964
identification of hsp90 as a stimulatory host factor involved in influenza virus rna synthesis.efficient transcription and replication of the influenza virus genome are dependent upon host-derived factors. using an in vitro rna synthesis system, we have purified and identified hsp90 as one of the host factors that stimulate viral rna polymerase activity. hsp90 interacted with the pb2 subunit of the viral rna polymerase through the amino-terminal chaperone domain and the middle region containing a highly acidic domain. the acidic middle region was also responsible for its stimulatory activ ...200212226087
[factors affecting the virulence and pathogenicity of avian and human viral strains (influenza virus type a)].most studies performed in avian viral strains seem to indicate that virulence is a polygenic phenomenon. however, hemagglutinin and neuraminidase and the genes codifying these substances (genes 4 and 6) play an essential role in viral pathogenesis. avian strains can be classified as avirulent or virulent according to the ability of hemagglutinin to be activated by endoproteases of the respiratory tract only or by proteases from other tissues. this ability is based on the progressive development ...200212237002
[the formation of the influenza virus aggregates, enriched with hemagglutinin].the formation of electrostatic aggregates was studied by analysis of two types of virus-containing liquids: initial warm liquid collected at temperature 37 degrees and the same liquid stored over the night at temperature 4 degrees c. the formation of virus aggregates was revealed at 4 degrees c. the aggregates formed at temperature 4 degrees c had a relatively high ha/np ratio in comparison with unassociated virus analyzed at 37 degrees. ha-enriched aggregates were found in the precipitate forme ...200212271719
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