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influenza a virus elevates active cathepsin b in primary murine dc.dendritic cells (dcs) act as a first-line recognition system for invading pathogens, such as influenza a. the interaction of dc with influenza a virus results in dc activation via endosomal toll-like receptors and also leads to presentation of viral peptides on mhc class ii molecules. prior work demonstrated that influenza a virus (a/hkx31; h3n2) infection of balb/c mice activates lung dcs for antigen presentation, and that the enhanced function of these cells persists long after viral clearance ...200717446210
neuraminidase inhibitor susceptibility of porcine h3n2 influenza a viruses isolated in germany between 1982 and 1999.as an intermediate host of avian and human influenza a viruses (fluav) pigs may play a potential role in interspecies virus transmission and reassortment of viral genes including those conferring antiviral drug resistance. porcine fluav isolated in germany between 1989 and 2001 contains mutations in the m2 gene inducing amantadine resistance. no data exist on neuraminidase inhibitor (nai) susceptibility of these porcine fluav. we studied the antiviral activity of nai against seven selected h3n2 ...200717445913
safety and immunogenicity of a baculovirus-expressed hemagglutinin influenza vaccine: a randomized controlled trial.a high priority in vaccine research is the development of influenza vaccines that do not use embryonated eggs as the substrate for vaccine production.200717426277
an amino acid substitution in the influenza a virus hemagglutinin associated with escape from recognition by human virus-specific cd4+ t-cells.influenza virus-specific cd4+ t-helper cells were cloned that recognized a virus strain isolated in 1981, but that failed to recognize more recent strains. the hla-dr*1601-restricted epitope recognized was located in the hemagglutinin (ha(99-113)) and the naturally occurring a-->v substitution at position 106 was responsible for abrogating the recognition by ha(99-113)-specific cd4+ t-cells. this amino acid substitution was found in influenza a/h3n2 viruses that circulated between 1999 and 2005 ...200717420064
comparison of neutralising antibody assays for detection of antibody to influenza a/h3n2 viruses: an international collaborative study.a study was performed to investigate the reproducibility of haemagglutinin-inhibition (hi) and virus neutralising (vn) assays for detection of anti-influenza antibody. participants in 11 laboratories from eight countries measured antibody to egg-grown a/japan/434/2003, cell-grown a/japan/434/2003 and a/panama/2007/99 (h3n2) viruses in 18 human and two post-infection ferret sera. there was significant intra-laboratory assay variability for vn compared to hi. for replicate assays within laboratori ...200717412461
a latex agglutination test for the rapid detection of avian influenza virus subtype h5n1 and its clinical application.a rapid and simple latex agglutination test (lat) for the detection of avian influenza virus (aiv) subtype h5n1 in chicken allantoic fluids, tracheal swabs, and tissues was developed. monoclonal antibodies against the hemagglutinin glycoprotein of h5n1 were covalently coupled onto the surface of carboxylated latex bead using a water-soluble carbodiimide to obtain sensitized latex particles (slp). these slps strongly agglutinated in the presence of allantoic fluid containing h5n1, but not fluids ...200717402609
efficacy of trivalent, cold-adapted, influenza virus vaccine against influenza a (fujian), a drift variant, during 2003-2004.in the 2003-2004 influenza season, the predominant circulating influenza a (h3n2) virus in the united states was similar antigenically to a/fujian/411/2002 (h3n2), a drift variant of a/panama/2007/99 (h3n2), the vaccine strain. that year, a field study of trivalent live-attenuated influenza vaccine (laiv-t) was conducted in temple-belton, texas, as part of a larger community-based, non-randomized, open-label study in three communities that began in august 1998 [gaglani mj, piedra pa, herschler g ...200717395338
nuclear and nucleolar targeting of influenza a virus ns1 protein: striking differences between different virus subtypes.influenza a virus nonstructural protein 1 (ns1a protein) is a virulence factor which is targeted into the nucleus. it is a multifunctional protein that inhibits host cell pre-mrna processing and counteracts host cell antiviral responses. we show that the ns1a protein can interact with all six human importin alpha isoforms, indicating that the nuclear translocation of ns1a protein is mediated by the classical importin alpha/beta pathway. the ns1a protein of the h1n1 (wsn/33) virus has only one n- ...200717376915
isolation and genetic analysis of human origin h1n1 and h3n2 influenza viruses from pigs in china.influenza a viruses of subtypes h1n1 and h3n2 have been reported widely in pigs, associated with clinical disease. these mainly include classical swine h1n1, avian-like h1n1, and human-like or avian-like h3n2 viruses. from 2005 to 2006, we carried out swine influenza virus surveillance in eight provinces of china. here we report, for the first time, the isolation and genetic analysis of a human-like influenza h1n1 virus from a pig in a farm of guangdong province of southern china, a host suspect ...200717346674
amino acid 226 in the hemagglutinin of h9n2 influenza viruses determines cell tropism and replication in human airway epithelial cells.influenza a viruses of the h9n2 subtype are endemic in poultry in many eurasian countries and have occasionally caused clinical respiratory diseases in humans. while some avian h9n2 viruses have glutamine (q) at amino acid position 226 of the hemagglutinin (ha) receptor-binding site, an increasing number of isolates have leucine (l) at this position, which has been associated with the establishment of stable lineages of the h2 and h3 subtypes of viruses in humans. little is known about the impor ...200717344280
influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin.influenza virus is a highly infectious respiratory pathogen that results in severe morbidity and mortality. the current licensed trivalent vaccine formulations in the u.s. are made from virus grown in allantoic fluid from infected hen eggs that is then chemically inactivated and split into subunit components. these vaccines elicit antibodies, primarily to the viral hemagglutinin (ha), which are efficacious in healthy adults, but are limited in protecting high risk individuals, such as the elderl ...200717337102
[influenza virus in pediatrics. a reason for hospitalization].influenza infection in infants and children has been classically underestimated due to its non-specific symptoms, which sometimes overlap those of other respiratory viruses. infants under 24 months are a risk group and school-aged children are a major source of influenza infection. the aim of this study was to describe the clinical and epidemiological characteristics of children hospitalized for flu, including co-infections and the differences as compared to other respiratory viruses. the effect ...200717335696
preclinical evaluation of microneedle technology for intradermal delivery of influenza vaccines.recent clinical studies have suggested that, for certain strains of influenza virus, intradermal (i.d.) delivery may enable protective immune responses using a lower dose of vaccine than required by intramuscular (i.m.) injection. here, we describe the first preclinical use of microneedle technology for i.d. administration of three different types of influenza vaccines: (i) a whole inactivated influenza virus, (ii) a trivalent split-virion human vaccine, and (iii) a plasmid dna encoding the infl ...200717329444
antibodies specific to the ha2 glycopolypeptide of influenza a virus haemagglutinin with fusion-inhibition activity contribute to the protection of mice against lethal infection.four monoclonal antibodies (mabs) recognizing distinct antigenic sites on the ha2 glycopolypeptide of influenza virus a/dunedin/4/73 (h3n2) have been tested for in vivo protection. when applied intravenously before infection, three of them increased the survival of balb/c mice infected with 1 ld50 homologous virus. the protection resulted simultaneously in 2 days earlier clearance of virus from the lungs. these three antibodies inhibited the fusion activity of virus in previous in vitro experime ...200717325369
hidden epitopes emerge in secondary influenza virus-specific cd8+ t cell responses.influenza a virus-specific cd8+ t cell responses in h2(b) mice are characterized by reproducible hierarchies. compensation by the d(b)pb1-f2(62) epitope is apparent following infection with a variant h3n2 virus engineered to disrupt the prominent d(b)np(366) and d(b)pa(224) epitopes (a double knockout or dko). analysis with a "triple" knockout (tko) virus, which also compromises d(b)pb1-f2(62), did not reveal further compensation to the known residual, minor, and predicted epitopes. however, inf ...200717312156
comparison of the mchip to viral culture, reverse transcription-pcr, and the quickvue influenza a+b test for rapid diagnosis of influenza.the performance of a diagnostic microarray (the mchip assay) for influenza was compared in a blind study to that of viral culture, reverse transcription (rt)-pcr, and the quickvue influenza a+b test. the patient sample data set was composed of 102 respiratory secretion specimens collected between 29 december 2005 and 2 february 2006 at scott & white hospital and clinic in temple, texas. samples were collected from a wide range of age groups by using direct collection, nasal/nasopharyngeal swabs, ...200717301287
influenza surveillance in korea: establishment and first results of an epidemiological and virological surveillance scheme.surveillance is an important component of influenza control. this report describes the establishment and first results of the korean influenza surveillance scheme (kiss), an integrated clinical and laboratory surveillance network involving 622 public health centres (phcs) and private clinics. sentinel physicians reported cases of influenza-like illness (ili) weekly and forwarded specimens for virus isolation and characterization. influenza activity during the opening 2000-2001 season was milder ...200717291376
antigenic and genetic evolution of swine influenza a (h3n2) viruses in europe.in the early 1970s, a human influenza a/port chalmers/1/73 (h3n2)-like virus colonized the european swine population. analyses of swine influenza a (h3n2) viruses isolated in the netherlands and belgium revealed that in the early 1990s, antigenic drift had occurred, away from a/port chalmers/1/73, the strain commonly used in influenza vaccines for pigs. here we show that italian swine influenza a (h3n2) viruses displayed antigenic and genetic changes similar to those observed in northern europea ...200717287258
design, synthesis, inhibitory activity, and sar studies of pyrrolidine derivatives as neuraminidase inhibitors.a series of pyrrolidine derivatives were synthesized and evaluated for their ability to inhibit neuraminidase (na) of influenza a virus (h3n2). all compounds were synthesized in good yields starting from commercially 4-hydroxy-l-proline using a suitable synthetic strategy. these compounds showed potent inhibitory activity against influenza a neuraminidase. within this series, five compounds, 6e, 9c, 9e, 9f, and 10e, have good potency (ic(50)=1.56-2.71 microm) which are compared to that the na in ...200717287121
performance testing of two new one-step real time pcr assays for detection of human influenza and avian influenza viruses isolated in humans and respiratory syncytial virus.two real time one-step rt-pcr assays were developed for simultaneous detection and typing of influenza a and b viruses and detection of respiratory syncytial virus (rsv). as regard influenza, primers were designed to amplify specific sequences of gene m of a/h1n1, a/h3n2, a/h5n1, a/h7n7 and a/h9n2 viruses and of gene np of type b viruses belonging both yamagata and victoria lineage. specificity, analytical and clinical sensitivity, dynamic range, linearity of the new assays were evaluated.200617263157
humoral and cellular immune responses in children given annual immunization with trivalent inactivated influenza vaccine.there have been no prior reports of the frequency of circulating influenza-specific, interferon gamma-producing memory cd4+ and cd8+ t-cells in healthy children who have received multiple influenza immunizations.200717259871
recombinant parainfluenza virus 5 (piv5) expressing the influenza a virus hemagglutinin provides immunity in mice to influenza a virus challenge.parainfluenza virus type 5 (piv5), formerly known as simian virus 5 (sv5), is a non-segmented negative strand rna virus that offers several advantages as a vaccine vector. piv5 infects many cell types causing little cytopathic effect, it replicates in the cytoplasm of infected cells, and does not have a dna phase in its life cycle thus avoiding the possibility of introducing foreign genes into the host dna genome. importantly, piv5 can infect humans but it is not associated with any known human ...200717254623
prevalence of pb1-f2 of influenza a viruses.pb1-f2 is a pro-apoptotic polypeptide of many influenza a virus (fluav) isolates encoded by an alternative orf of segment 2. a comprehensive genbank search was conducted to analyse its prevalence. this search yielded 2226 entries of 80 fluav subtypes. of these sequences, 87 % encode a pb1-f2 polypeptide greater than 78 aa. however, classic swine influenza viruses and human h1n1 isolates collected since 1950 harbour a truncated pb1-f2 sequence. while pb1-f2 of human h1n1 viruses terminates after ...200717251572
assessment of the extent of variation in influenza a virus cytotoxic t-lymphocyte epitopes by using virus-specific cd8+ t-cell clones.the influenza a virus nucleoprotein (np) and matrix protein are major targets for human virus-specific cytotoxic t-lymphocyte (ctl) responses. most of the ctl epitopes that have been identified so far are conserved. however, sequence variation in ctl epitopes of the np has recently been demonstrated to be associated with escape from virus-specific ctls. to assess the extent of variation in ctl epitopes during influenza a virus evolution, 304 ctl clones derived from six study subjects were obtain ...200717251571
[influenza in poland in 2004].a total number of 336,919 cases of influenza and influenza-like illness registered in poland in 2004 (incidence 882.4 per 100 000 population). regionally the incidence ranged from 226.2 per 100 000 population in podlaskie to 2,122.3 in mazowieckie. children and adolescents under 15 years of age accounted for 30.5% of all cases (age specific incidence 1,588.2 per 100,000). in this age group the incidence varied regionally from 388,7 in slaskie to 3,718.2 in mazowieckie. 1,038 patients (0.31% of a ...200617249160
amantadine-resistant influenza a (h3n2) virus in japan, 2005-2006. 200717229966
serologic surveillance of swine h1 and h3 and avian h5 and h9 influenza a virus infections in swine population in korea.influenza a is a respiratory disease common in the swine industry. three subtypes, h1n1, h1n2 and h3n2 influenza a viruses, are currently co-circulating in swine populations in korea. an outbreak of the highly pathogenic avian influenza h5n1 virus occurred in domestic bird farms in korea during the winter season of 2003. pigs can serve as hosts for avian influenza viruses, enabling passage of the virus to other mammals and recombination of mammalian and avian influenza viruses, which are more re ...200717223213
epidemiology of influenza in hanoi, vietnam, from 2001 to 2003.the aim of this study was to clarify the epidemiology of laboratory-confirmed influenza in hanoi, vietnam.200717222912
features discriminating sars from other severe viral respiratory tract infections.this study investigated the discriminatory features of severe acute respiratory syndrome (sars) and severe non-sars community-acquired viral respiratory infection (requiring hospitalization) in an emergency department in hong kong. in a case-control study, clinical, laboratory and radiological data from 322 patients with laboratory-confirmed sars from the 2003 sars outbreak were compared with the data of 253 non-sars adult patients with confirmed viral respiratory tract infection from 2004 in or ...200717219094
non-compact nucleocapsid protein multimers in influenza-virus-infected cells.we have previously shown that protease-resistant and highly immunoreactive compact np oligomers, dissociating at +80 degrees c and possessing properties of folded proteins, are post-translationally formed in influenza-virus-infected cells. in this study we demonstrate that, in addition to compact np oligomers, incompletely folded np multimers are detected intracellularly by sds/page carried out under weak dissociating conditions. in cells infected with avian, human a(h2n2), and human a(h3n2) vir ...200717216139
[the properties of the epidemic influenza viruses a and b strains circulating in russia in the 2004-2005 epidemic season].the epidemic upsurge of influenza morbidity in russia in 2004-2005 was caused by the active circulation of influenza a(h3n2) and b viruses. a hundred and sixty-six epidemic strains were studied. all the strains were isolated in the mck cell culture. influenza a(h3n2) viruses (n=77) were antigenic variants of the reference a/fujian/411/ 2002 and a/california/7/2004 strains. three influenza a(h1n1) viral strains that were antigenic variants of a/new caledonia/20/99 strains were isolated in sporadi ...200617214079
a comparison of the humoral and cellular immune responses at different immunological sites after split influenza virus vaccination of mice.the spleen, bone marrow and lymph nodes are all known to be important organs for the initiation and maintenance of an immune response after vaccination. to investigate the differences and similarities in the humoral and cellular immune responses between these tissues, we vaccinated mice once or twice with the conventional human dose (15 microg ha) of influenza a (h3n2) split virus vaccine and analysed the sera and lymphocytes collected from the different sites. we found that the response of anti ...200717212762
avian-virus-like receptor specificity of the hemagglutinin impedes influenza virus replication in cultures of human airway epithelium.a non-optimal receptor-binding specificity of avian influenza viruses is believed to hamper their replication in humans; however, the magnitude of this restriction remains undefined. here we generated recombinant viruses, r1 and r2, that differed solely by two amino acids in the receptor-binding site of their hemagglutinin (ha). r1 harbored the original ha of the pandemic human virus a/hong kong/1/68 (h3n2), whereas r2 was the l226q/s228g ha mutant with avian-virus-like receptor specificity. in ...200717207830
comparative analytical sensitivities of six rapid influenza a antigen detection test kits for detection of influenza a subtypes h1n1, h3n2 and h5n1.rapid and simple methods for diagnosing human influenza a (h5n1) disease urgently needed. the limited data so far suggest that the currently available rapid antigen detection kits have poor clinical sensitivity for diagnosis of human h5n1 disease.200717194622
identification of a/h5n1 influenza viruses using a single gene diagnostic microarray.in previous work, a simple diagnostic dna microarray that targeted only the matrix gene segment of influenza a (mchip) was developed and evaluated with patient samples. in this work, the analytical utility of the mchip for detection and subtyping of an emerging virus was evaluated with a diverse set of a/h5n1 influenza viruses. a total of 43 different highly pathogenic a/h5n1 viral isolates that were collected from diverse geographic locations, including vietnam, nigeria, indonesia, and kazakhst ...200717194164
[influenza associated excess mortality in argentina: 1992-2002].to describe the effect of influenza on mortality in argentina, from 1992 to 2002.200617186076
changes in paracrine interleukin-2 requirement, ccr7 expression, frequency, and cytokine secretion of human immunodeficiency virus-specific cd4+ t cells are a consequence of antigen load.virus-specific cd4+ t-cell responses are thought to be required for the induction and maintenance of many effective cd8+ t-cell and b-cell immune responses in experimental animals and humans. although the presence of human immunodeficiency virus (hiv)-specific cd4+ t cells has been documented in patients at all stages of hiv infection, many fundamental questions regarding their frequency and function remain. a 10-color, 12-parameter flow cytometric panel was utilized to examine the frequency, me ...200717182676
anti-influenza virus activities of 4-[(1,2-dihydro-2-oxo-3h-indol-3-ylidene)amino]-n-(4,6-dimethyl-2-pyrimidin-2-yl)benzenesulphonamide and its derivatives.4-[(1,2-dihydro-2-oxo-3h-indol-3-ylidene)amino]-n-(4,6-dimethyl-2-pyrimidinyl)-benzenesulphonamide (spiii-5h) and related compounds were tested for antiviral activity against influenza a (h1n1, h3n2, and h5n1) and b viruses in madin darby canine kidney (mdck) cell culture. among the compounds tested, spiii-5h and four derivatives (5-chloro [spill-5cl], 5-bromo [spiii-5br], 5-methyl [spiii-5me] and n-acetyl [spiii-na]) showed similar antiviral potencies, with only the 5-fluoro (spiii-5f) derivati ...200617176631
rimantadine and oseltamivir demonstrate synergistic combination effect in an experimental infection with type a (h3n2) influenza virus in mice.we studied the combination effect of rimantadine hydrochloride and oseltamivir phosphate on mice infected with influenza a/aichi/2/68 (h3n2) virus. compounds were simultaneously administered in a 5-day-treatment course, starting 4 h before intranasal infection with 10 or 20 viral 50% mouse lethal doses. initially, we tested combinations of oseltamivir (0.05, 0.1 and 0.2 mg/kg/day) and rimantadine (2.5, 5.0 and 7.5 mg/kg/day). significant differences were recorded between combination-treated grou ...200617176629
lower clinical effectiveness of oseltamivir against influenza b contrasted with influenza a infection in children.recently, many japanese physicians have claimed that oseltamivir is less effective in children with influenza b virus infection. this study assesses the effectiveness of oseltamivir against influenza a (h3n2) and influenza b in children on the basis of the duration of febrile illness.200717173216
prevention of antigenically drifted influenza by inactivated and live attenuated vaccines.the efficacy of influenza vaccines may decline during years when the circulating viruses have antigenically drifted from those included in the vaccine.200617167134
natural course of fever during influenza virus infection in children.during the 2001-2002 epidemic of influenza virus a/h1n1, a/h3n2, and b, the authors obtained detailed profiles of fever from 118 infected children. the only treatment given was acetaminophen for temperatures greater than 39.0 degrees c. fever was most prominent in a/h3n2 and young children. secondary fever was observed frequently at 72 to 132 hours in all types. the duration of fever was associated negatively with the age of the child and positively with the maximal temperature. the information ...200717164515
antiviral management of seasonal and pandemic influenza.the goals of antiviral treatment for influenza are to decrease symptoms and functional disability and, more important, to decrease associated complications, hospitalizations, and mortality. four drugs have been approved for treatment of and prophylaxis against influenza in the united states, but they are underutilized. the m2 ion channel inhibitors amantadine and rimantadine are effective for prophylaxis, and they decrease the duration of symptoms if they are used for early treatment of influenz ...200617163384
influenza virus pleiomorphy characterized by cryoelectron tomography.influenza virus remains a global health threat, with millions of infections annually and the impending threat that a strain of avian influenza may develop into a human pandemic. despite its importance as a pathogen, little is known about the virus structure, in part because of its intrinsic structural variability (pleiomorphy): the primary distinction is between spherical and elongated particles, but both vary in size. pleiomorphy has thwarted structural analysis by image reconstruction of elect ...200617146053
stochastic processes are key determinants of short-term evolution in influenza a virus.understanding the evolutionary dynamics of influenza a virus is central to its surveillance and control. while immune-driven antigenic drift is a key determinant of viral evolution across epidemic seasons, the evolutionary processes shaping influenza virus diversity within seasons are less clear. here we show with a phylogenetic analysis of 413 complete genomes of human h3n2 influenza a viruses collected between 1997 and 2005 from new york state, united states, that genetic diversity is both abu ...200617140286
proteinase inhibitors from streptomyces with antiviral activity.an extensive screening study for the production of proteolytic inhibitors has been carried out on 75 streptomyces strains. it was found that 18 of the strains and/or their variants (24%) produced proteinaceous substances, which belonged to the group of typical serine protease inhibitors. 23 samples were tested for inhibitory activity on the replication of influenza virus a/germany/34, strain rostock (h7n1) (a/rostock) in chicken embryonic fibroblast (cef) cells. eleven of the tested samples (52. ...200617139614
using sentinel surveillance to monitor effectiveness of influenza vaccine is feasible: a pilot study in denmark.the influenza vaccine for the season 2003/04 did not contain the circulating a(h3n2)/fujian virus strain. vaccine effectiveness (ve) estimates were needed but unavailable. we explored whether or not laboratory based influenza surveillance can be used to estimate ve. we carried out a case-control study nested within danish sentinel surveillance. a case was defined as a person aged 25 or above with a(h3n2)/fujian/411/02 influenza. four controls per case, matched on age groups and time, were select ...200617130655
chemoenzymatic synthesis of artificial glycopolypeptides containing multivalent sialyloligosaccharides with a gamma-polyglutamic acid backbone and their effect on inhibition of infection by influenza viruses.highly water-soluble, artificial glycopolypeptides with a gamma-polyglutamic acid (gamma-pga) backbone derived from bacillus subtilis sp. and multivalent sialyloligosaccharide units have been chemoenzymatically synthesized as potential polymeric inhibitors of infection by bird and human influenza viruses. 5-trifluoroacetamidopentyl beta-n-acetyllactosaminide and 5-trifluoroacetamidopentyl beta-lactoside were enzymatically synthesized from lacnac and lactose, respectively, by cellulase-mediated c ...200717129732
characterization of multidrug-resistant influenza a/h3n2 viruses shed during 1 year by an immunocompromised child.development of influenza drug resistance is an important problem in immunocompromised children that could result in treatment failure and viral transmission to others.200617109288
virus associated hemophagocytic syndrome accompanied by acute respiratory failure caused by influenza a (h3n2).a 40-year-old japanese woman was admitted to oita university hospital with progressive dyspnea, consciousness disturbance and severe cytopenias. her chest roentgenogram showed diffuse bilateral infiltrates. she was therefore forced to receive mechanical ventilation. bone marrow aspiration disclosed numerous hemophagocytic histiocytes, thus suggesting her condition to be hemophagocytic syndrome. in addition, she also developed myocarditis and renal failure. pulsed methylprednisolone, gamma-globul ...200617106167
subtyping of influenza a isolates in taiwan--2003 to 2004.some isolated influenza strains are untypable. the possibility that a novel and potentially lethal strain, such as h5 virus, might be one of these untypable strains remains a major concern. this study investigated the nature of untypable influenza strains in taiwan.200617098691
[peptide mapping of the monoclonal antibodies against the heavy chain hemagglutinin from influenza virus h3n2].interaction of the synthetic peptides corresponding to the regions 122-133, 136-147, 154-164 and 314-328 of the virus a/aichi/2/68 hemagglutinin heavy chain with monoclonal antibodies specific for this hemagglutinin was assayed in a variety of tests, e.g., elisa, competition ria, hemagglutinin-inhibition and virus-neutralization assays. the monoclonal antibody 152 reacted with the area 136-147 (epitope a), three monoclonal antibodies 3, 19 and 63 reacted exclusively with the area (154-164) glu ( ...200617094654
response to influenza vaccine in people with non-protective hi antibody titers.the purpose of the study was to determine which factors correlate directly with response to vaccination in such a group of subjects with non-protective hi antibody titers before vaccination. two vaccines were used, a subunit virus vaccine adjuvanted with mf59 and a split virus vaccine. the analysis indicated that immunization with vaccine adjuvanted with mf59 was an independent variable for immune response against a/h3n2 (or: 3.51; 95% ci: 1.81-6.79) and b (or: 2.31; 95% ci: 1.37-3.89). the resu ...200617082899
[avian influenza viruses--new causative agents of human infections].introduction: influenza a viruses can infect humans, some mammals and especially birds. subtypes of human influenza a viruses: a(h1n1), a(h2n2) and a(h3n2) have caused pandemics. avian influenza viruses vary owing to their 15 hemagglutinins (h) and 9 neuraminidases (n). human cases of avian influenza a: in the netherlands in 2003, there were 83 human cases of influenza a (h7n7). in 1997, 18 cases of h5n1 influenza a, of whom 6 died, were found among residents of hong kong. in 2004, 34 human case ...200617068888
long intervals of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza a virus.the interpandemic evolution of the influenza a virus hemagglutinin (ha) protein is commonly considered a paragon of rapid evolutionary change under positive selection in which amino acid replacements are fixed by virtue of their effect on antigenicity, enabling the virus to evade immune surveillance.200617067369
[an adult case of acute cerebellitis after influenza a infection with a cerebellar corical lesion on mri].we report an adult case of acute cerebellitis associated with influenza a. a 25-year-old woman with fever and headache was diagnosed as having influenza a infection, because nasal swab extract was found positive in the influenza assay. she was treated with oseltamivir. after the treatment, she gradually developed gait and speech disturbance. neurological examination revealed dysarthria with scanning slurred speech, and limb and truncal ataxia. cerebrospinal fluid showed pleocytosis and a four-fo ...200617061703
rapid sequencing of the non-coding regions of influenza a virus.the non-coding regions (ncrs) of influenza a virus gene segments play a crucial role in the viral replication cycle. although the ncrs are considered to be conserved, some variation does exist, that affects viral replication. therefore, a rapid method to sequence the 5' and 3' ncrs was designed. this method is based on ligation of viral rna, rt reactions and subsequent pcr with primersets consisting of a gene segment specific primer and a primer designed across the junction of the 5' and 3' ends ...200717059848
dose-related safety and immunogenicity of baculovirus-expressed trivalent influenza vaccine: a double-blind, controlled trial in adult patients with non-hodgkin b cell lymphoma.in 27 patients randomized to receive commercial trivalent influenza vaccine (tiv) containing 15 microg of the hemagglutinin (ha) of influenza a (h3n2 and h1n1) and b virus or a recombinant vaccine (rhao) containing 15, 45, or 135 microg of each ha, reactogenicity was minor. among patients with similar prevaccination titers, 40% given 45 microg and 60% given 135 microg of rhao developed an increase in influenza a/h3 neutralizing antibody levels; there were no increases in 4 given tiv. for each va ...200617054068
[surveillance for influenza a virus infections in infants and young children in beijing, china, 2001-2005].to characterize the prevalence and antigenic drift of influenza a viruses isolated during the period from 2001 to 2005 in infants and young children in beijing.200617044978
phase i, randomized, controlled trial to study the reactogenicity and immunogenicity of a nasal, inactivated trivalent influenza virus vaccine in healthy adults.we performed a randomized, placebo-controlled, dose-escalating clinical trial to evaluate the safety and immunogenicity of an inactivated, split virion, trivalent, nasal influenza vaccine using lipid/polysaccharide molecules as carriers. a total of 64 adults (mean age 29; range 19-69 years) were randomly allocated to receive a mixture of lipid/polysaccharide carrier molecules and 7.5, 15, or 30 microg hemagglutinin antigen of each of the three influenza strains (a/johannesburg/82/96 [h1n1], a/na ...200517038827
a non-living nasal influenza vaccine can induce major humoral and cellular immune responses in humans without the need for adjuvants.twenty-eight healthy adult volunteers were immunized intranasally with an inactivated whole-virus influenza vaccine based on the strain a/new caledonia/20/99 (h1n1), either in saline or mixed with formaldehyde-inactivated bordetella pertussis as a mucosal adjuvant, or in a thixotropic vehicle with mucoadhesive properties. after four doses, all groups of vaccinees developed significant igg- and iga-antibody responses, measured by elisa, in respectively serum and nasal secretions. none of the volu ...200517038826
[expression of host genes in influenza virus infected cells].when nci-h292 human bronchial epithelial cells were infected with influenza a/udorn/72(h3n2) virus, 152 host genes were identified as virus-stimulated genes (vsgs). the expression of these genes was increased more than 4-fold by the virus infection and reached to the level of more than one copy per cell. seventy-three vsgs were also stimulated by interferon-beta (ifn-beta) treatment and they contained the genes known to possess antiviral activity. as a likely consequence, the production of proge ...200617037354
reassortment between human a(h3n2) viruses is an important evolutionary mechanism.phylogenetic relationships of whole genomes of h3n2 viruses circulating in germany during a 6-year period from 1998 to 2005 revealed the co-circulation of different lineages of viruses. multiple reassortment events occurred during this time between viruses belonging to different lineages or different subgroups. strains isolated during 1998-1999 were characterised by a surprisingly high heterogeneity and multiple reassortment events. seventy percent of the examined 1998-1999 viruses had completel ...200617030498
longitudinal analysis of genotype distribution of influenza a virus from 2003 to 2005.influenza a viruses cause yearly epidemics, in part, due to their ability to overcome immunity from previous infections through acquisition of mutations. amino acid sequences encoded by genes 4 (ha), 6 (na), 7 (m), and 8 (ns) from 77 h3n2 influenza a isolates, collected between november 2003 and march 2005, were analyzed to determine the extent to which the viruses mutated within epidemic periods and between the epidemics. nucleotide and amino acid sequences were stable throughout the epidemics ...200617021086
antibody responses after dose-sparing intradermal influenza vaccination.reduced-dose intradermal (id) influenza vaccination is an attractive approach to increase availability of vaccine supply in an event of vaccine shortage. we conducted a randomized open-label study, in which 500 subjects were randomly assigned to receive an id injection of 0.1 ml dose of inactivated split-virion influenza vaccine or an im injection of 0.5 ml dose. the subjects who had hemagglutination inhibition (hi) antibody titer of at least 1:40 at day 28 post-vaccination in id and im groups w ...200717011678
superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections.young children have a high incidence of influenza and influenza-related complications. this study compared the efficacy and safety of cold-adapted influenza vaccine, trivalent (caiv-t) with trivalent inactivated influenza vaccine (tiv) in young children with a history of recurrent respiratory tract infections (rtis).200617006279
primary influenza a virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice.in order to assess the level of protection against a lethal influenza virus infection provided by a primary infection with a virus strain of another subtype, c57bl/6 mice were infected with the sublethal influenza virus x-31 (h3n2) and subsequently challenged with the lethal strain a/pr/8/34 (h1n1). the outcome of the challenge infection was compared with that in mice that did not experience an infection with influenza virus x-31 prior to the challenge infection. the x-31 experienced mice cleare ...200717005299
serological profiles after consecutive experimental infections of pigs with european h1n1, h3n2, and h1n2 swine influenza viruses.swine influenza viruses (sivs) of h1n1, h3n2, and h1n2 subtypes, with antigenically different hemagglutinins, are currently cocirculating in pigs in europe. this study aimed to determine whether the hemagglutination inhibition (hi) test, which is the primary serological test for siv, is sufficiently specific to discriminate between infections with the three subtypes. in experiment 1, pigs were consecutively inoculated with european h1n1, h3n2, and h1n2 sivs by the intranasal route, or with the r ...200616987057
inhibition of multiple subtypes of influenza a virus in cell cultures with morpholino oligomers.peptide-conjugated phosphorodiamidate morpholino oligomers (p-pmo) are single-stranded nucleic acid-like antisense agents that can reduce gene expression by sterically blocking complementary rna sequence. p-pmo are water soluble and nuclease resistant, and they readily achieve uptake into cells in culture under standard conditions. eight p-pmo, each 20 to 22 bases in length, were evaluated for their ability to inhibit influenza a virus (fluav) a/pr/8/34 (h1n1) replication in cell culture. the p- ...200616966399
evaluation of hemagglutinin subtype 1 swine influenza viruses from the united states.swine influenza viruses (siv) of the hemagglutinin subtype 1 (h1) isolated from the united states (u.s.) have not been well-characterized in the natural host. an increase in the rate of mutation and reassortment has occurred in siv isolates from the u.s. since 1998, including viruses belonging to the h1 subtype. two independent animal studies were done to evaluate and compare the pathogenesis of 10 siv isolates dating from 1930 to currently circulating isolates. in addition, the hemagglutinin an ...200616962262
immunization with trivalent inactivated influenza vaccine in partially immunized toddlers.children > or = 6 months of age who have previously received 1 dose of trivalent inactivated influenza vaccine are recommended to be given an additional single trivalent inactivated influenza vaccine dose the following fall. limited data exist documenting the immunogenicity of 2 doses of influenza vaccine given in separate years to young children, and it is not known if the antigen content of each of the 2 doses of vaccine must be identical or similar to optimally immunize children in this age g ...200616950949
a fused gene of nucleoprotein (np) and herpes simplex virus genes (vp22) induces highly protective immunity against different subtypes of influenza virus.we evaluated the immunogenicity and protective activity of plasmid dna vaccines encoding the influenza virus np gene (pnp) alone or in combination with the herpes simplex virus type 1 protein 22 gene (pvp22). optimal immune responses were observed in balb/c mice immunized with the combination of pvp22 plus pnp, as assessed by enzyme-linked immunosorbent assay (elisa), enzyme-linked immunospot (elispot) and intracellular cytokine staining (iccs). these mice also showed maximal resistance followin ...200616945400
vaccination of pigs against swine influenza viruses by using an ns1-truncated modified live-virus vaccine.swine influenza viruses (siv) naturally infect pigs and can be transmitted to humans. in the pig, genetic reassortment to create novel influenza subtypes by mixing avian, human, and swine influenza viruses is possible. an siv vaccine inducing cross-protective immunity between different subtypes and strains circulating in pigs is highly desirable. previously, we have shown that an h3n2 siv (a/swine/texas/4199-2/98 [tx98]) containing a deleted ns1 gene expressing a truncated ns1 protein of 126 ami ...200616943300
overcoming maternal antibody interference by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of swine influenza virus.sows and gilts lack immunity to human adenovirus 5 (ad-5) vectored vaccines so immunogens of swine pathogens can be expressed with these vaccines in order to immunize suckling piglets that have interfering, maternally derived antibodies. in this study 7-day-old piglets, that had suckled h3n2 infected gilts, were sham-inoculated with a non-expressing ad-5 vector or given a primary vaccination with replication-defective ad-5 viruses expressed the h3 hemagglutinin and the nucleoprotein of swine inf ...200616939702
virus-epitope vaccine design: informatic matching the hla-i polymorphism to the virus genome.attempts to develop peptide vaccines, based on a limited number of peptides face two problems: hla polymorphism and the high mutation rate of viral epitopes. we have developed a new genomic method that ensures maximal coverage and thus maximal applicability of the peptide vaccine. the same method also promises a large number of epitopes per hla to prevent escape via mutations. our design can be applied swiftly in order to face rapidly emerging viral diseases. we use a genomic scan of all candida ...200716930710
influenza a outbreak in a community hospital.in january 2005, the department of public health, hse eastern region, received notification of an outbreak of influenza-like illness (ili) in a community hospital for elderly patients. influenza a (h3n2 subtype) was isolated in 12 of 18 (66%) throat swabs sent to the national virus reference laboratory (nvrl). an outbreak control team was convened. infection control measures were put in place. immunisation clinics were organised for non-immunised staff. the epidemic curve confirmed peak onset of ...200616921823
addition of a prominent epitope affects influenza a virus-specific cd8+ t cell immunodominance hierarchies when antigen is limiting.a reverse genetics strategy was used to insert the ova peptide (amino acid sequence siinfekl; ova(257-264)) into the neuraminidase stalk of both the a/pr8 (h1n1) and a/hkx31 (h3n2) influenza a viruses. initial characterization determined that k(b)ova257 is presented on targets infected with pr8-ova and hk-ova without significantly altering d(b) nucleoprotein (np)366 presentation. there were similar levels of k(b)ova257- and d(b)np366-specific ctl expansion following both primary and secondary in ...200616920927
importance of neuraminidase active-site residues to the neuraminidase inhibitor resistance of influenza viruses.neuraminidase inhibitors (nais) are antivirals designed to target conserved residues at the neuraminidase (na) enzyme active site in influenza a and b viruses. the conserved residues that interact with nais are under selective pressure, but only a few have been linked to resistance. in the a/wuhan/359/95 (h3n2) recombinant virus background, we characterized seven charged, conserved na residues (r118, r371, e227, r152, r224, e276, and d151) that directly interact with the nais but have not been r ...200616912325
a cell-based luminescence assay is effective for high-throughput screening of potential influenza antivirals.the spread of highly pathogenic avian influenza across geographical and species barriers underscores the increasing need for novel antivirals to compliment vaccination and existing antiviral therapies. identification of new antiviral lead compounds depends on robust primary assays for high-throughput screening (hts) of large compound libraries. we have developed a cell-based screen for potential influenza antivirals that measures the cytopathic effect (cpe) induced by influenza virus (a/udorn/72 ...200716904762
outbreak of influenza amongst residential school students in malaysia.in the months of july and august 2003, an outbreak of acute respiratory illness caused by influenza a virus occurred among students in seven residential schools situated in the northern part (perak) of peninsular malaysia. out of 4989 students, aged 13 to 18 years (mean = 15.9), 1419 (28%) were effected by influenza-like illness. all patients were treated as outpatients except for 36 students who required admission for high fever, severe coughing and shortness of breath. abnormal chest x-ray fin ...200616898307
impaired long-chain fatty acid metabolism in mitochondria causes brain vascular invasion by a non-neurotropic epidemic influenza a virus in the newborn/suckling period: implications for influenza-associated encephalopathy.the neuropathogenesis of influenza-associated encephalopathy in children and reye's syndrome remains unclear. a surveillance effort conducted during 2000-2003 in south-west japan reveals that almost all fatal and handicapped influenza-associated encephalopathy patients exhibit a disorder of mitochondrial beta-oxidation with elevated serum acylcarnitine ratios (c(16:0)+c(18:1))/c(2). here we show invasion by a non-neurotropic epidemic influenza a h3n2 virus in cerebral capillaries with progressiv ...200716896540
mutations conferring zanamivir resistance in human influenza virus n2 neuraminidases compromise virus fitness and are not stably maintained in vitro.viruses resistant to zanamivir have been generated in vitro, but no resistant virus has yet been isolated from a zanamivir-treated immunocompetent patient. in contrast most resistant viruses isolated from oseltamivir-treated patients correspond to those selected in vitro. however, despite mutations being in conserved residues in the neuraminidase (na) they do not confer resistance in all na subtypes.200616891631
experimental evaluation of the fluchip diagnostic microarray for influenza virus surveillance.global surveillance of influenza is critical for improvements in disease management and is especially important for early detection, rapid intervention, and a possible reduction of the impact of an influenza pandemic. enhanced surveillance requires rapid, robust, and inexpensive analytical techniques capable of providing a detailed analysis of influenza virus strains. low-density oligonucleotide microarrays with highly multiplexed "signatures" for influenza viruses offer many of the desired char ...200616891504
lack of transmission of h5n1 avian-human reassortant influenza viruses in a ferret model.avian influenza a h5n1 viruses continue to spread globally among birds, resulting in occasional transmission of virus from infected poultry to humans. probable human-to-human transmission has been documented rarely, but h5n1 viruses have not yet acquired the ability to transmit efficiently among humans, an essential property of a pandemic virus. the pandemics of 1957 and 1968 were caused by avian-human reassortant influenza viruses that had acquired human virus-like receptor binding properties. ...200616880383
influenza-related mortality in the italian elderly: no decline associated with increasing vaccination coverage.we investigated trends in influenza-related mortality among the elderly population in italy associated with increased vaccination coverage. using italian vital statistics data, we studied monthly death rates for pneumonia and influenza and all-cause for persons >/=65 years of age by 5-year age groups for 1970-2001. using a classic seasonal regression modelling approach, we estimated the age-specific seasonal excess mortality rates among italian elderly as a measure of influenza-related deaths. w ...200616876293
prevention and control of influenza: recommendations of the advisory committee on immunization practices (acip).this report updates the 2005 recommendations by the advisory committee on immunization practices (acip) regarding the use of influenza vaccine and antiviral agents (cdc. prevention and control of influenza: recommendations of the advisory committee on immunization practices [acip]. mmwr 2005;54[no. rr-8]:1--44). the 2006 recommendations include new and updated information. principal changes include 1) recommending vaccination of children aged 24-59 months and their household contacts and out-of- ...200616874296
infection of human airway epithelium by human and avian strains of influenza a virus.we describe the characterization of influenza a virus infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (hae). sialic acid receptors for both human and avian viruses, alpha-2,6- and alpha-2,3-linked sialic acids, respectively, were detected on the hae cell surface, and their distribution accurately reflected that in human tracheobronchial tissue. nonciliated cells present a higher proportion of alpha-2,6-linked sialic acid, while ciliated cells po ...200616873262
evidence of a cross-protective immune response to influenza a in the cotton rat model.epidemiologic evidence suggests that cross-protective immune responses to influenza a viruses that have different hemagglutinin and neuraminidase subtypes occur in humans. this study characterized this heterosubtypic immunity in cotton rats (sigmodon hispidus). animals were infected with influenza a/pr/8/34 (h1n1) or a/wuhan/359/95 (h3n2), and then challenged with a/wuhan/359/95(h3n2) virus 4 weeks later. viral titers, respiratory rates, and pathology of the respiratory tract following primary a ...200616860444
genomic analysis of influenza a viruses, including avian flu (h5n1) strains.this study was designed to conduct genomic analysis in two steps, such as the overall relative synonymous codon usage (rscu) analysis of the five virus species in the orthomyxoviridae family, and more intensive pattern analysis of the four subtypes of influenza a virus (h1n1, h2n2, h3n2, and h5n1) which were isolated from human population. all the subtypes were categorized by their isolated regions, including asia, europe, and africa, and most of the synonymous codon usage patterns were analyzed ...200616858618
identification of genetic diversity by cultivating influenza a(h3n2) virus in vitro in the presence of post-infection sera from small children.antigenic variants probably arise in the field by escaping herd immunity. we have earlier found that sera from small children are more strain-specific than sera from adults and could therefore, provide favourable conditions for selecting antigenic escape mutants. we had access to small volumes of anonymous sera collected in norway after the epidemic season 1999/00, which was dominated by the a/panama/2007/99 (h3n2) variant. the ha gene of the representative strain of that season was genetically ...200616844271
natural selection on the influenza virus genome.influenza viruses are the etiological agents of influenza. although vaccines and drugs are available for the prophylaxis and treatment of influenza virus infections, the generation of escape mutants has been reported. to develop vaccines and drugs that are less susceptible to the generation of escape mutants, it is important to understand the evolutionary mechanisms of the viruses. here natural selection operating on all the proteins encoded by the h3n2 human influenza a virus genome was inferre ...200616818477
[adamantane resistance among influenza a (h3n2) viruses isolated from the mainland of china].to study the incidence of adamantane resistance among influenza a (h3n2) viruses isolated from the mainland of china since 1989 through our influenza surveillance system, and to provide more information for the clinical usage of adamantane drugs.200616816855
single amino acid substitutions in the hemagglutinin of influenza a/singapore/21/04 (h3n2) increase virus growth in embryonated chicken eggs.most of the recently circulating h3n2 influenza a strains do not replicate well in embryonated chicken eggs and had to be isolated by cell culture, which presents a great challenge for influenza vaccine production using embryonated chicken eggs. we previously reported that a human h3n2 virus, a/fujian/411/02, which replicates poorly in eggs, could be improved by changing a minimum of two ha residues (g186v/v226i or h183l/v226a). here, we extended our work to the a/singapore/21/04 strain that was ...200616814431
amantadine resistance among porcine h1n1, h1n2, and h3n2 influenza a viruses isolated in germany between 1981 and 2001.this study was designed to gain insight into amantadine susceptibility of porcine influenza a viruses isolated in germany between 1981 and 2001. the 12 studied h1n1, h1n2, and h3n2 porcine influenza virus strains were isolated in chicken eggs and passaged once in mdck cells. plaque reduction assays were applied to examine virus susceptibility to amantadine. genotyping was used to confirm drug resistance. in the results of these antiviral studies, only 3 of the 12 isolates were shown to be amanta ...200616809934
[sequence analysis of the ha1 regions of hemagglutinin genes of influenza viruses (h3n2) isolated from children in beijing from 1998 - 2004].to characterize the ha1 regions of hemagglutinin gene of influenza viruses (h3n2) isolated from children in beijing from 1998 - 2004.200616792896
[diagnostics of viral respiratory infections in hospitalized patients and ambulatory patients from sentinel program during 2004/05 season in poland].the aim of the study was to evaluate an impact of respiratory infections on the study population, type/subtype of influenza viruses circulating during 2004/05 season within the groups of hospitalised (n=35) and ambulatory patients (n=420) and to determine antigenic affinity of isolated viral strains. laboratory diagnostics of influenza a and b type, rsv, adenovirus and parainfluenzavirus (type 1, 2 and 3) was performed using direct immunofluorescence test (difa), virus isolation on mdck cell lin ...200516789521
the guinea pig as a transmission model for human influenza viruses.the severity of epidemic and pandemic influenza outbreaks is dictated in part by the efficiency with which the causative strain transmits between human hosts. the mechanisms underlying influenza virus spread are poorly understood, in part because of the lack of a convenient animal model to study this phenomenon. indeed, despite extremely efficient transmission among humans and virulence in the mouse model, we have shown that even the 1918 pandemic influenza virus does not transmit between mice. ...200616785447
[influenza diagnostics in patient with leukemia suspicion].influenza is a seasonal viral disease, with the peak of morbidity occurring in poland between january and march. it is estimated that up to 70% of respiratory infections during the season is caused by this virus. influenza virus infection poses an ultimate threat to the elderly > or = 65 years old and chronically ill, in whom postinfluenzal complications--including viral pneumonia and secondary bacterial pneumonia--cause from 0.1% to 0.4% deaths annually. influenza also triggers off from 5% to 7 ...200616780271
cross-reactivity of influenza a (h3n2) hemagglutination-inhibition antibodies induced by an inactivated influenza vaccine.the antigenic drift of influenza a (h3n2) virus in 2003-2004 necessitated a change in the vaccine from the a/panama to the a/wyoming strain for the 2004-2005 season. using hemagglutination inhibition, we therefore tested antibodies in sera of 39 individuals (mean age 64.6 years) at the end of the 2003-2004 season for cross-reactivity to vaccine strains and h3n2 antigens subject to antigenic drift. antibodies against both a (h3n2) panama and wyoming developed in 5/13 (38.5%) unvaccinated individu ...200616777274
epidemiological and virological assessment of influenza activity in europe, during the 2004-2005 winter.the 2004-2005 influenza season in europe started in late december 2004 and the first influenza activity occurred in the west and southwest (spain, united kingdom and ireland). influenza activity then moved gradually east across europe during january and early february 2005, and from late february until late march, most movement was south to north. the intensity of clinical influenza activity in ten out of 23 countries was higher than during the 2003-2004 season, and lower or equal to the 2003-20 ...200616757850
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