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glycan analysis and influenza a virus infection of primary swine respiratory epithelial cells: the importance of neuac{alpha}2-6 glycans.to better understand influenza virus infection of pigs, we examined primary swine respiratory epithelial cells (srecs, the primary target cells of influenza viruses in vivo), as a model system. glycomic profiling of srecs by mass spectrometry revealed a diverse range of glycans terminating in sialic acid or galαgal. in terms of sialylation, α2-6 linkage was more abundant than α2-3, and neuac was more abundant than neugc. virus binding and infection experiments were conducted to determine functio ...201020724471
avian-origin h3n2 canine influenza a viruses in southern china.this study reports four sporadic cases of h3n2 canine influenza in southern china, which were identified from sick dogs from may 2006 to october 2007. the evolutionary analysis showed that all eight segments of these four viruses are avian-origin and phylogenetically close to the h3n2 canine influenza viruses reported earlier in south korea. systematic surveillance is required to monitor the disease and evolutionary behavior of this virus in canine populations in china.201020732458
genetic correlation between current circulating h1n1 swine and human influenza viruses.h1n1 is the main subtype influenza a virus circulating in human and swine population, and has long been a threat to economy and public health.201020732830
serological characterization of guinea pigs infected with h3n2 human influenza or immunized with hemagglutinin protein.recent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses. therefore guinea pig may be a useful animal model for better understanding influenza infection and assessing vaccine strategies. to more fully characterize the model, antibody responses following either infection/re-infection with human influenza a/wyoming/03/2003 h3n2 or immunization with its homologous recombinant hemagglutinin (ha) protein were studied.201020735849
seroepidemiology of pandemic influenza a (h1n1) 2009 virus infections in pune, india.in india, pune was one of the badly affected cities during the influenza a (h1n1) 2009 pandemic. we undertook serosurveys among the risk groups and general population to determine the extent of pandemic influenza a (h1n1) 2009 virus infections.201020738878
clinical importance and impact on the households of oseltamivir-resistant seasonal a/h1n1 influenza virus in healthy children in italy.a resistance of a/h1n1 influenza viruses to oseltamivir has recently emerged in a number of countries. however, the clinical and socioeconomic importance of this resistance has not been precisely defined. as children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal a/h1n1 influenza virus in an otherwise healthy pediatric populat ...201020738882
the impact of the pandemic influenza a(h1n1) 2009 virus on seasonal influenza a viruses in the southern hemisphere, 2009.data collected over winter 2009 by five world health organisation national influenza centres in the southern hemisphere were used to examine the circulation of pandemic and seasonal influenza a strains during the first pandemic wave in the southern hemisphere.there is compelling evidence that the pandemic influenza a(h1n1) 2009 virus significantly displaced seasonal influenza a(h1n1) and, to a lesser extent, a(h3n2) viruses circulating in the southern hemisphere. complete replacement of seasonal ...201020738990
influenza antiviral prescribing practices during the 2007-08 and 2008-09 influenza seasons in the setting of increased resistance to oseltamivir among circulating influenza viruses.in december 2008, new interim guidelines on the use of influenza antiviral agents were released in response to a high prevalence of circulating oseltamivir-resistant seasonal influenza a(h1n1) and adamantane-resistant influenza a(h3n2) viruses. zanamivir, oseltamivir +/- an adamantane, or oseltamivir was recommended, depending on virus type, subtype, and local surveillance data.201020739002
rapid detection of respiratory tract viral infections and coinfections in patients with influenza-like illnesses by use of reverse transcription-pcr dna microarray systems.we prospectively tested 95 nasal swabs or nasopharyngeal aspirates taken from 56 adults and 39 children visiting the reims university medical centre (northern france) for influenza-like illnesses (ili) during the early stage of the french influenza a/h1n1v pandemic (october 2009). respiratory samples were tested using a combination of two commercially available reverse transcription-pcr (rt-pcr) dna microarray systems allowing rapid detection of influenza a virus strains, including the new a/h1n ...201020739481
[swine-origin influenza h1n1/california--passions and facts].analysis of pandemic caused by swine influenza virus h1n1/california showed moderate virulence of this virus compared to pandemic viruses, which caused pandemics in 1918, 1957, and 1968. during seasonal influenza epidemic in countries of southern hemisphere (june-august 2009) despite on circulation of h1n1/california strain, epidemics was caused by human influenza viruses h3n2 and h1n1. it was concluded that strain h1n1/california could not be attributed to pandemic strains of influenza viruses.201020795393
production and antigenic properties of influenza virus from suspension mdck-siat7e cells in a bench-scale bioreactor.in efforts to overcome limitations associated with egg-based influenza vaccines, mammalian cell substrates have gradually emerged as potential production platforms. recently, a suspension madin darby canine kidney (mdck) cell line for influenza virus production was created by expressing the human siat7e gene. to examine the broad susceptibility of this novel cell line, the scalability of the production process, and the antigenic stability of cell-derived progeny viruses, infection experiments us ...201020800699
genetic content of influenza h3n2 vaccine seeds.influenza vaccine seeds produced in chicken eggs are selected through ha and na surface glycoproteins antigenicity, as well as through high replicative ability. here we characterize the genetic content of recently used thirteen h3n2 influenza vaccine seeds. interestingly, sequence analysis of the vaccine seeds shows reassortment events leading to pr8:h3n2 segment constellations, ranging from the 6:2 to 2:6 constellations. this study shows that the h3n2 pb1 is the most frequent internal segment i ...201020802842
policy statement--recommendations for prevention and control of influenza in children, 2010-2011.the purpose of this statement is to update current recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. the 2009 influenza a (h1n1) pandemic virus is expected to circulate, with infants and children at increased risk of severe illness and death. this year's trivalent seasonal influenza vaccine contains a/california/7/2009 (h1n1)-like antigen (derived from the 2009 pandemic influenza a [h1n1] v ...201020805143
genetic divergence of influenza a ns1 gene in pandemic 2009 h1n1 isolates with respect to h1n1 and h3n2 isolates from previous seasonal epidemics.the influenza a pandemic sustained by a new h1n1 variant (h1n1v) started in mexico and the usa at the end of april 2009 spreading worldwide in a few weeks. in this study we investigate the variability of the ns1 gene of the pandemic h1n1v strain with respect to previous seasonal strains circulating in humans and the potential selection of virus variants through isolation in cell culture.201020809948
serological response in rt-pcr confirmed h1n1-2009 influenza a by hemagglutination inhibition and virus neutralization assays: an observational study.we describe the serological response following h1n1-2009 influenza a infections confirmed by reverse-transcriptase polymerase chain reaction (rt-pcr).201020814575
neonates investigated for influenza-like illness during the outbreak of pandemic h1n1 2009: trivial infections but major triage implications.we report eight cases of neonates (from birth to 25 days) admitted to the neonatal service of a teaching hospital with influenza-like illness during the outbreak of pandemic h1n1 2009, and discuss their management and infection control issues. empirical antibiotics were often promptly initiated and timely stopped when sepsis was ruled out. also, there was no pandemic h1n1-09 but influenza a (h3n2, n = 1), parainfluenza (type 3, n = 3) and respiratory syncytial virus (n = 1) have been isolated. t ...201020814838
amantadine resistance in relation to the evolution of influenza a(h3n2) viruses in iran.the aminoadamantanes, amantadine and rimantadine, have been used to prevent and treat influenza a virus infections for many years. several reports have shown an increased level of resistance to these drugs, particularly among influenza a(h3n2) subtype viruses, during recent years. we observed an increase in amantadine resistance, due to a ser31asn mutation in the m2 channel protein, among a(h3n2) viruses circulating in iran during 2005-2007. sequence analyses of the haemagglutinin and neuraminid ...201020816700
molecular characteristics of the human pandemic influenza a virus (h1n1).the outbreak of the human pandemic influenza a (h1n1) has caused a considerable public concern. the aim of this review was to improve our understanding of this novel virus by analyzing the relationships between its molecular characteristics and pathogenic properties. results of this analysis indicate that the human pandemic influenza a (h1n1) virus is a new re-assorted virus, which combines genetic materials from the avian flu (h1n1) virus, classical swine flu (h1n1) virus, human flu (h3n2) viru ...201020822307
enhanced immunogenicity of stabilized trimeric soluble influenza hemagglutinin.the recent swine-origin h1n1 pandemic illustrates the need to develop improved procedures for rapid production of influenza vaccines. one alternative to the current egg-based manufacture of influenza vaccine is to produce a hemagglutinin (ha) subunit vaccine using a recombinant expression system with the potential for high protein yields, ease of cloning new antigenic variants, and an established safety record in humans.201020824188
reassortant between human-like h3n2 and avian h5 subtype influenza a viruses in pigs: a potential public health risk.human-like h3n2 influenza viruses have repeatedly been transmitted to domestic pigs in different regions of the world, but it is still uncertain whether any of these variants could become established in pig populations. the fact that different subtypes of influenza viruses have been detected in pigs makes them an ideal candidate for the genesis of a possible reassortant virus with both human and avian origins. however, the determination of whether pigs can act as a "mixing vessel" for a possible ...201020830295
a comprehensive surveillance of adamantane resistance among human influenza a virus isolated from mainland china between 1956 and 2009.adamantane-derived drugs have been used for treatment and prophylaxis of influenza a virus infection for many years worldwide. rapid surveillance of antiviral drug resistance is important for appropriate clinical guideline development. here, we retrospectively assessed adamantane resistance among different influenza a subtypes (h1n1, h3n2 and h5n1) over 53 years (1956-2009) in mainland china.201020834097
[history of pandemic influenza in japan].in japan, influenza like epidemics were described many times since heian era. however, spanish flu as the modern medicine invaded japan in 1918, thus almost infected 390,000 patients died with associated pneumonia. after the discovery of influenza virus in 1933, japan experienced pandemic influenza--asian flu(h2n2) in 1957. after about 10 years, hong kong flu (h3n2) came to japan at 1968. however, we had many reliable antibiotics but had not any antiviral drug at the early time. after year 2000, ...201020845733
an influenza b outbreak during the 2007/2008 winter among appropriately immunized elderly people living in a nursing home.the study evaluated the immunogenicity and efficacy of a trivalent subunit mf59-adjuvanted influenza vaccine (a/wisconsin/67/05 (h3n2), a/solomon islands/3/06 (h1n1) and b/malaysia/2506/04) in preventing serologically diagnosed infections in a group of 67 institutionalized elderly volunteers during 2007/2008 winter, characterized by co-circulation of drifted a/h3n2, a/h1n1 and b influenza viruses. influenza vaccination induced a significant increase in the amounts of hemagglutination inhibiting ...201020846530
development of a novel bead-based multiplex pcr assay for combined subtyping and oseltamivir resistance genotyping (h275y) of seasonal and pandemic h1n1 influenza a viruses.the identification of influenza a virus subtypes in clinical specimens is becoming increasingly important for clinical laboratories since seasonal h1n1, h3n2 and pandemic h1n1 influenza a viruses can have defined antiviral resistance patterns and subtyping can be used as a surrogate for antiviral resistance testing.201020846903
influenza a virus replication induces cell cycle arrest in g0/g1 phase.many viruses interact with the host cell division cycle to favor their own growth. in this study, we examined the ability of influenza a virus to manipulate cell cycle progression. our results show that influenza a virus a/wsn/33 (h1n1) replication results in g(0)/g(1)-phase accumulation of infected cells and that this accumulation is caused by the prevention of cell cycle entry from g(0)/g(1) phase into s phase. consistent with the g(0)/g(1)-phase accumulation, the amount of hyperphosphorylated ...201020861262
evaluation of a new rapid influenza a diagnostic test for detection of pandemic (h1n1) 2009 and seasonal influenza a virus.rapid influenza a diagnostic tests (ridts) play an important role in the clinical setting, especially in the influenza post-pandemic era with three influenza a viruses in circulation.201021051280
[cross immunity study of two different influenza a3 virus vaccine strain].to explore the cross immunity response between two similar strains of influenza a3 virus vaccine from 2007 to 2008.201021055127
evaluation of the cellular immune responses induced by a non-adjuvanted inactivated whole virus a/h5n1/vn/1203 pandemic influenza vaccine in humans.in the present study the homologous and heterologous type and subtype specific cellular immune response induced by a wild type inactivated whole virus h5n1 influenza (a/vietnam/1203/2004) vaccine was evaluated. two immunizations with the vero cell derived h5n1 influenza vaccine on day 0 and day 21 induced significant h5n1 vaccine specific and h5 haemagglutinin specific clade and cross-clade reactive cd4(+) t cell responses, which were maintained at significant levels for at least 6 months. the h ...201021055500
discovery of novel benzoquinazolinones and thiazoloimidazoles, inhibitors of influenza h5n1 and h1n1 viruses, from a cell-based high-throughput screen.a highly reproducible and robust cell-based high-throughput screening (hts) assay was adapted for screening of small molecules for antiviral activity against influenza virus strain a/vietnam/1203/2004 (h5n1). the nih molecular libraries small molecule repository (mlsmr) molecular libraries screening centers network (mlscn) 100,000-compound library was screened at 50 µm. the "hit" rate (>25% inhibition of the viral cytopathic effect) from the single-dose screen was 0.32%. the hits were evaluated ...201021059874
determinants of glycan receptor specificity of h2n2 influenza a virus hemagglutinin.the h2n2 subtype of influenza a virus was responsible for the asian pandemic of 1957-58. however, unlike other subtypes that have caused pandemics such as h1n1 and h3n2, which continue to circulate among humans, h2n2 stopped circulating in the human population in 1968. strains of h2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. such an event is a potential global health concern because of t ...201021060797
protective efficacy of seasonal influenza vaccination against seasonal and pandemic influenza virus infection during 2009 in hong kong.the relationship between seasonal influenza vaccine and susceptibility to 2009 pandemic a/h1n1 virus infection is not fully understood.201021067351
origin of the 1918 pandemic h1n1 influenza a virus as studied by codon usage patterns and phylogenetic analysis.the pandemic of 1918 was caused by an h1n1 influenza a virus, which is a negative strand rna virus; however, little is known about the nature of its direct ancestral strains. here we applied a broad genetic and phylogenetic analysis of a wide range of influenza virus genes, in particular the pb1 gene, to gain information about the phylogenetic relatedness of the 1918 h1n1 virus. we compared the rna genome of the 1918 strain to many other influenza strains of different origin by several means, in ...201021068184
localization of epitopes recognized by monoclonal antibodies that neutralized the h3n2 influenza viruses in man.through extensive isolation of neutralizing mabs against h3n2 influenza viruses representing the in vivo repertoire in a human donor, we examined the relationships between antigenic drift of influenza virus and protective antibodies generated in an infected individual. the majority of mabs isolated from a donor born in 1960 were divided into three major groups with distinct strain specificity: 1968-1973, 1977-1993 and 1997-2003. in the present study, we developed a new method that allowed us to ...201021068214
efficacy of oseltamivir-zanamivir combination compared to each monotherapy for seasonal influenza: a randomized placebo-controlled trial.neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. the objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo.201021072246
singleplex real-time rt-pcr for detection of influenza a virus and simultaneous differentiation of a/h1n1v and evaluation of the realstar influenza kit.a novel influenza a virus, subtype a/h1n1v emerged in april 2009 and caused the first influenza pandemic of the 21st century. reliable detection and differentiation from seasonal influenza viruses is mandatory for appropriate case management as well as public health.201021075679
phylogenetic analysis of swine influenza viruses isolated in poland.swine influenza virus (siv) of h1n1 and h3n2 subtypes are dominated in european pigs population. "classical swine" h1n1 subtype was replaced by "avian-like" h1n1 subtype. it co-circulates with h3n2 reassortant possessing "avian" genes. in the present study, 41 siv strains isolated from pigs with pneumonia, raised in 20 polish farms, were identified and characterised. since it was evidenced that isolates from the same geographic district and the same year of isolation are in 100% similar, 15 stra ...201021077429
transmission of a 2009 pandemic influenza virus shows a sensitivity to temperature and humidity similar to that of an h3n2 seasonal strain.in temperate regions of the world, influenza epidemics follow a highly regular seasonal pattern, in which activity peaks in midwinter. consistently with this epidemiology, we have shown previously that the aerosol transmission of a seasonal h3n2 influenza virus is most efficient under cold, dry conditions. with the 2009 h1n1 pandemic, an exception to the standard seasonality of influenza developed: during 2009 in the northern hemisphere, an unusually high level of influenza virus activity over t ...201021084485
selective pressure to increase charge in immunodominant epitopes of the h3 hemagglutinin influenza protein.the evolutionary speed and the consequent immune escape of h3n2 influenza a virus make it an interesting evolutionary system. charged amino acid residues are often significant contributors to the free energy of binding for protein-protein interactions, including antibody-antigen binding and ligand-receptor binding. we used markov chain theory and maximum likelihood estimation to model the evolution of the number of charged amino acids on the dominant epitope in the hemagglutinin protein of circu ...201021086120
a diagnostic algorithm for detection of antibodies to influenza a viruses in dogs in italy (2006-2008).since 2004, there have been several reports of influenza a virus (fluav) infection in dogs. dogs have been infected with equine influenza h3n8, avian influenza h3n2 and h5n1, and the pandemic h1n1 virus. because of recent avian and equine influenza outbreaks in italy, the objectives of the present study were to estimate the level of exposure of italian dogs to influenza a viruses and to assess a diagnostic algorithm for detection of fluav exposure in dogs. sera collected from 6,858 dogs from 200 ...201021088175
replicon particle vaccine protects swine against influenza.an alphavirus derived replicon particle (rp) vaccine expressing the cluster iv h3n2 swine influenza virus (siv) hemagglutinin (ha) gene induced protective immunity against homologous influenza virus challenge. however, pigs with maternal antibody had no protective immunity against challenge after vaccination with rp vaccines expressing ha gene alone or in combination with nucleoprotein gene.201021094422
phenotypic and genotypic characterization of influenza virus mutants selected with the sialidase fusion protein das181.influenza viruses (ifvs) frequently achieve resistance to antiviral drugs, necessitating the development of compounds with novel mechanisms of action. das181 (fludase), a sialidase fusion protein, may have a reduced potential for generating drug resistance due to its novel host-targeting mechanism of action.201021097900
the i222v neuraminidase mutation has a compensatory role in replication of an oseltamivir-resistant influenza virus a/h3n2 e119v mutant.oseltamivir-resistant a/h3n2 influenza isolates with or without the e119v and i222v neuraminidase (na) mutations were recovered from an immunocompromised patient. based on plaque size, yield assays, and na activity, the impaired viral fitness of the e119v mutant was partially restored by the i222v na mutation.201021106781
[preparation of vero cell-adapted influenza h5n1 virus strain by genetic reassortment].to prepare vero cell-adapted influenza h5n1 virus strain by genetic reassortment and produce influenza h5n1 vaccine using vero cell as a substrate.201021110431
seroprevalence and risk factors of swine influenza in spain.swine influenza is caused by type a influenza virus. pigs can be infected by both avian and human influenza viruses; therefore, the influenza virus infection in pigs is considered an important public health concern. the aims of present study were to asses the seroprevalence of swine influenza subtypes in spain and explore the risk factors associated with the spread of those infections. serum samples from 2151 pigs of 98 randomly selected farms were analyzed by an indirect elisa for detection of ...201021112702
genetic diversity of h9n2 influenza viruses from pigs in china: a potential threat to human health?pandemic strains of influenza a virus might arise by genetic reassortment between viruses from different hosts. pigs are susceptible to both human and avian influenza viruses and have been proposed to be intermediate hosts or mixing vessels, for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. in this study, we summarize and report for the first time the coexistence of 10 (a-j) genotypes in pigs in china by analyzing the eight genes of 28 swi ...201021115230
a novel sequence-based antigenic distance measure for h1n1, with application to vaccine effectiveness and the selection of vaccine strains.h1n1 influenza causes substantial seasonal illness and was the subtype of the 2009 influenza pandemic. precise measures of antigenic distance between the vaccine and circulating virus strains help researchers design influenza vaccines with high vaccine effectiveness. we here introduce a sequence-based method to predict vaccine effectiveness in humans. historical epidemiological data show that this sequence-based method is as predictive of vaccine effectiveness as hemagglutination inhibition assa ...201021123189
intranasal immunization with influenza vlps incorporating membrane-anchored flagellin induces strong heterosubtypic protection.we demonstrated previously that the incorporation of a membrane-anchored form of flagellin into influenza virus-like particles (vlps) improved the immunogenicity of vlps significantly, inducing partially protective heterosubtypic immunity by intramuscular immunization. because the efficacy of mucosal vaccination is highly dependent on an adjuvant, and is particularly effective for preventing mucosal infections such as influenza, we determined whether the membrane-anchored flagellin is an efficie ...201021124769
guinea pig model for evaluating the potential public health risk of swine and avian influenza viruses.the influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. animal models to evaluate the potential public health risk potential of these viruses are needed.201021124850
network analysis of global influenza spread.although vaccines pose the best means of preventing influenza infection, strain selection and optimal implementation remain difficult due to antigenic drift and a lack of understanding global spread. detecting viral movement by sequence analysis is complicated by skewed geographic and seasonal distributions in viral isolates. we propose a probabilistic method that accounts for sampling bias through spatiotemporal clustering and modeling regional and seasonal transmission as a binomial process. a ...201021124942
redundancy of the influenza a virus-specific cytotoxic t lymphocyte response in hla-b*2705 transgenic mice limits the impact of a mutation in the immunodominant np(383-391) epitope on influenza pathogenesis.during the 1993-1994 flu season, influenza a/h3n2 viruses emerged with an amino acid substitution (r384g) at the anchor residue of the hla-b*2705 restricted np(383-391) epitope located in the nucleoprotein (np). the r384g substitution reached fixation rapidly and abrogated recognition of a/h3n2 viruses by np(383-391)-specific cd8+ t cytotoxic t lymphocytes (ctl) completely. to test the impact of the r384g substitution in the immunodominant np(383-391) epitope in vivo, influenza a viruses that di ...201020863862
detection of excess influenza severity: associating respiratory hospitalization and mortality data with reports of influenza-like illness by primary care physicians.we explored whether excesses in influenza severity can be detected by combining respiratory syndromic hospital and mortality data with data on influenza-like illness (ili) cases obtained from general practitioners.201020864730
comparison of pro-inflammatory cytokine expression and cellular signal transduction in human macrophages infected with different influenza a viruses.influenza a virus infection of macrophages and virus-induced pro-inflammatory gene expression are regarded to contribute to severity of influenza a virus-caused diseases. although some data are available on cytokine production by influenza a virus-infected macrophages, systematic comparisons of the virus types are currently considered to be of high relevance in humans (pandemic h1n1/2009, seasonal h1n1, seasonal h3n2, highly pathogenic avian influenza h5n1) on pro-inflammatory potential, and rel ...201020865277
pandemic h1n1 and seasonal h3n2 influenza infection in the human population show different distributions of viral loads, which substantially affect the performance of rapid influenza tests.a wide range of sensitivity has been reported for rapid influenza antigen tests (riat). in this study, we analyzed the viral loads of 778 pandemic h1n1- and 227 seasonal h3n2-virus positive clinical specimens collected during the same period and found that viral loads in pandemic h1n1 viruses was characterized by lower copy numbers than seasonal h3n2 viruses. among various factors including the timing of specimen collection, patient age, patient gender and subtype of influenza, we found that the ...201020875469
seroprevalence of seasonal and pandemic influenza a viruses in domestic cats.infection of domestic cats with pandemic h1n1 influenza virus has recently been documented. we conducted a seroprevalence survey and found that 17 of 78 (21.8%) cats sampled during the 2009-2010 influenza season had antibody titers ≥40 against the novel h1n1 strain by hemagglutinin-inhibition assay, compared to only 1 of 39 (2.6%) sampled in 2008 prior to emergence of the pandemic (p = 0.006). seroprevalance of seasonal h1n1 (41.9%) and h3n2 (25.6%) viruses was similarly high. these data reflect ...201020878192
characterization of an h3n2 triple reassortant influenza virus with a mutation at the receptor binding domain (d190a) that occurred upon virus transmission from turkeys to pigs.the hemagglutinin (ha) protein of influenza virus mediates essential viral functions including the binding to host receptor and virus entry. it also has the antigenic sites required for virus neutralization by host antibodies. here, we characterized an h3n2 triple reassortant (tr) influenza virus (a/turkey/ohio/313053/04) with a mutation at the receptor binding domain (asp190ala) that occurred upon virus transmission from turkeys to pigs in an experimental infection study. the mutant virus repli ...201020920297
influence of an additional amino group on the potency of aminoadamantanes against influenza virus a. ii - synthesis of spiropiperazines and in vitro activity against influenza a h3n2 virus.spiro[piperidine-2,2'-adamantane] 4 is one of the most potent synthetic anti-influenza a aminoadamantanes or other cage structure amines tested so far. based on previous results tataridis et al. (2007) [5h] which demonstrate the boost of in vitro potency by the presence of an additional amino group, we examined whether the incorporation of a second amino group into this heterocycle would increase the anti-influenza a virus activity. the new synthetic molecules 5-7 are capable of forming two hydr ...201020926112
contrasting substitution patterns between ha proteins of avian and human influenza viruses: implication for monitoring human influenza epidemics.the ha1 domain of influenza a viruses is critical for immune escape and host receptor recognition. however, the association between ha1 evolution and host species-specific adaptations remains unclear. we have identified the amino acid sites that are related to the host species-specific adaptations by systematically comparing the evolutionary dynamics of ha1 between human and avian hosts for both h1n1 and h3n2 viruses. we can thus refine the "positively selected sites" in the ha1 domain of these ...201020933040
influenza a virus strains that circulate in humans differ in the ability of their ns1 proteins to block the activation of irf3 and interferon-β transcription.we demonstrate that influenza a virus strains that circulate in humans differ markedly in the ability of their ns1 proteins to block the activation of irf3 and interferon-β transcription. strong activation occurs in cells infected with viruses expressing ns1 proteins of seasonal h3n2 and h2n2 viruses, whereas activation is blocked in cells infected with viruses expressing ns1 proteins of some, but not all seasonal h1n1 viruses. the ns1 proteins of the 2009 h1n1 and h5n1 viruses also block these ...201020934196
glycan shielding of the influenza virus hemagglutinin contributes to immunopathology in mice.pandemic influenza viruses historically have had few potential sites for n-linked glycosylation on the globular head of the hemagglutinin (ha) on emergence from the avian reservoir. gain of glycans within antigenic sites of the ha during adaptation to the mammalian lung facilitates immune evasion.201020935106
inhibition of lectin-mediated innate host defences in vivo modulates disease severity during influenza virus infection.host-mediated recognition of mannose-rich glycans on the surface of pathogens represents an ancient mechanism of innate immune defence. in this study, we demonstrate that the virus strains that differ in the degree of n-linked glycosylation on the globular head of their hemagglutinin glycoprotein also differed in their (i) sensitivity to neutralization by a mannose-specific lectin in mouse lung fluids and (ii) ability to infect (and, therefore, to be destroyed) by airway macrophages. virus strai ...201020938455
possible role of aerosol transmission in a hospital outbreak of influenza.we examined the role of aerosol transmission of influenza in an acute ward setting.201020942655
multiplexed, rapid detection of h5n1 using a pcr-free nanoparticle-based genomic microarray assay.for more than a decade there has been increasing interest in the use of nanotechnology and microarray platforms for diagnostic applications. in this report, we describe a rapid and simple gold nanoparticle (np)-based genomic microarray assay for specific identification of avian influenza virus h5n1 and its discrimination from other major influenza a virus strains (h1n1, h3n2).201020942949
combination of peramivir and rimantadine demonstrate synergistic antiviral effects in sub-lethal influenza a (h3n2) virus mouse model.efficacy of combination of the intramuscularly administered neuraminidase (na) inhibitor, peramivir, and the orally administered m2 ion channel blocker, rimantadine was evaluated in mouse influenza a/victoria/3/75 (h3n2) model. mice were challenged with a sub-lethal virus dose (0-40% mortality in placebo group) and changes in body weights were analyzed by three-dimensional effect analysis to assess mode of drug interactions. compounds were administered in a 5-day treatment course starting 1h bef ...201020943201
cationic lipid/dna complex-adjuvanted influenza a virus vaccination induces robust cross-protective immunity.influenza a virus is a negative-strand segmented rna virus in which antigenically distinct viral subtypes are defined by the hemagglutinin (ha) and neuraminidase (na) major viral surface proteins. an ideal inactivated vaccine for influenza a virus would induce not only highly robust strain-specific humoral and t-cell immune responses but also cross-protective immunity in which an immune response to antigens from a particular viral subtype (e.g., h3n2) would protect against other viral subtypes ( ...201020943978
influenza antigen-sparing by immune stimulation with gram-positive enhancer matrix (gem) particles.gram-positive enhancer matrix (gem) particles, produced from non-genetically modified lactococcus lactis bacteria have an inherent immunostimulatory activity. it was investigated whether co-administration of gem particles can reduce the amount of influenza subunit vaccine (ha) necessary to protect mice from viral infection. decreasing ha amounts of 5, 1, 0.2 and 0.04μg admixed with gem particles were tested in intramuscular immunizations. combinations of gem and seasonal ha (a/wisconsin/67/2005 ...201020946860
transforming growth factor-β: activation by neuraminidase and role in highly pathogenic h5n1 influenza pathogenesis.transforming growth factor-beta (tgf-β), a multifunctional cytokine regulating several immunologic processes, is expressed by virtually all cells as a biologically inactive molecule termed latent tgf-β (ltgf-β). we have previously shown that tgf-β activity increases during influenza virus infection in mice and suggested that the neuraminidase (na) protein mediates this activation. in the current study, we determined the mechanism of activation of ltgf-β by na from the influenza virus a/gray teal ...201020949074
vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes.current influenza virus vaccines protect mostly against homologous virus strains; thus, regular immunization with updated vaccine formulations is necessary to guard against the virus' hallmark remodeling of regions that mediate neutralization. development of a broadly protective influenza vaccine would mark a significant advance in human infectious diseases research. antibodies with broad neutralizing activity (nabs) against multiple influenza virus strains or subtypes have been reported to bind ...201020956293
transmission of influenza a viruses between pigs and people, iowa, 2002-2004.triple-reassortant (tr) viruses of human, avian, and swine origin, including h1n1, h1n2, and h3n2 subtypes, emerged in north american swine herds in 1998 and have become predominant. while sporadic human infections with classical influenza a (h1n1) and with tr-swine influenza viruses have been reported, relatively few have been documented in occupationally exposed swine workers (sw).201020958933
analysis of synonymous codon usage bias in 09h1n1.a novel subtype of influenza a virus 09h1n1 has rapidly spread across the world. evolutionary analyses of this virus have revealed that 09h1n1 is a triple reassortant of segments from swine, avian and human influenza viruses. in this study, we investigated factors shaping the codon usage bias of 09h1n1 and carried out cluster analysis of 60 strains of influenza a virus from different subtypes based on their codon usage bias. we discovered that more preferentially used codons of 09h1n1 are a-ende ...201020960179
modifications in the polymerase genes of a swine-like triple-reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic h1n1 viruses.on 11 june 2009, the world health organization (who) declared that the outbreaks caused by novel swine-origin influenza a (h1n1) virus had reached pandemic proportions. the pandemic h1n1 (h1n1pdm) virus is the predominant influenza virus strain in the human population. it has also crossed the species barriers and infected turkeys and swine in several countries. thus, the development of a vaccine that is effective in multiple animal species is urgently needed. we have previously demonstrated that ...201020962084
potential role of viral surface glycoproteins in the replication of h3n2 triple reassortant influenza a viruses in swine and turkeys.the h3n2 triple reassortant (tr) influenza viruses emerged in swine in 1998 and then in turkeys in 2003. it was then hypothesized that these viruses crossed the species barrier and transmitted from pigs to turkeys. in previous work we identified viruses with different transmission behavior between the two species, of which a/turkey/ohio/313053/04 (tk04) transmitted both ways between swine and turkeys, and a/swine/north carolina/03 (sw03) did not transmit either way between the two species. utili ...201020965669
genomic signature-based identification of influenza a viruses using rt-pcr/electro-spray ionization mass spectrometry (esi-ms) technology.the emergence and rapid spread of the 2009 h1n1 pandemic influenza a virus (h1n1pdm) in humans highlights the importance of enhancing the capability of existing influenza surveillance systems with tools for rapid identification of emerging and re-emerging viruses. one of the new approaches is the rt-pcr electrospray ionization mass spectrometry (rt-pcr/esi-ms) technology, which is based on analysis of base composition (bc) of rt-pcr amplicons from influenza "core" genes. combination of the bc si ...201020967258
single-dose mucosal immunization with a candidate universal influenza vaccine provides rapid protection from virulent h5n1, h3n2 and h1n1 viruses.the sudden emergence of novel influenza viruses is a global public health concern. conventional influenza vaccines targeting the highly variable surface glycoproteins hemagglutinin and neuraminidase must antigenically match the emerging strain to be effective. in contrast, "universal" vaccines targeting conserved viral components could be used regardless of viral strain or subtype. previous approaches to universal vaccination have required protracted multi-dose immunizations. here we evaluate a ...201020976273
outbreaks of pandemic (h1n1) 2009 and seasonal influenza a (h3n2) on cruise ship.to determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (h1n1) 2009 and influenza a (h3n2) that had occurred on a cruise ship in may 2009. of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (h1n1) 2009 virus, 98 (3.6%) with influenza a (h3n2) virus, and 2 (0.1%) with both. among 45 children who visited the ship's childcare center, infection rate for pandemic (h1n1) 2009 was hi ...201021029531
one-step real-time reverse transcription-pcr assays for detecting and subtyping pandemic influenza a/h1n1 2009, seasonal influenza a/h1n1, and seasonal influenza a/h3n2 viruses.pandemic influenza a/h1n1 2009 (a/h1n1pdm) virus has caused significant outbreaks worldwide. a previous one-step real-time reverse transcription-pcr (rrt-pcr) assay for detecting a/h1n1pdm virus (h1pdm rrt-pcr assay) was improved since the former probe had a low melting temperature and low tolerance to viral mutation. to help with the screening of the a/h1n1pdm virus, rrt-pcr assays were also developed for detecting human seasonal a/h1n1 (h1 rrt-pcr assay) and a/h3n2 influenza viruses (h3 rrt-pc ...201021029748
[in vivo efficacy of ingavirin against pandemic a (h1n1/09)v influenza virus].ingavirin was shown to be efficient in inhibition of the pandemic influenza virus strains a/california/04/2009 (h1n1)v, a/california/07/2009 (h1n1)v, a/moscow/225/2009 (h1n1)v and a/moscow/226/2009 (h1n1)v. as well as the influenza virus strain a/aichi/2/68 (h3n2) in the lungs of the infected mice. after oral administration of ingavirin the titers of the influenza virus strains in the lung homogenates lowered.201021033472
investigation of the influence of eps® 7630, a herbal drug preparation from pelargonium sidoides, on replication of a broad panel of respiratory viruses.the pelargonium sidoides extract eps® 7630 is an approved drug for the treatment of acute bronchitis in germany. the postulated mechanisms underlying beneficial effects of eps® 7630 in bronchitis patients include immunomodulatory and cytoprotective effects, inhibition of interaction between bacteria and host cells, and increase of cilliary beat frequency on respiratory cells. here, we investigated the influence of eps® 7630 on replication of a panel of respiratory viruses. determination of virus ...201021036571
prolonged shedding of amantadine- and oseltamivir-resistant influenza a(h3n2) virus with dual mutations in an immunocompromised infant.in this study, we report a case of multidrug-resistant influenza a(h3n2) virus isolated from an immunosuppressed patient with prolonged viral shedding. we also describe the genetic characterization of the haemagglutinin, neuraminidase and m2 influenza genes. the virus contained the substitutions e119v in neuraminidase and v27a in m2, which produce resistance to oseltamivir and adamantanes, respectively. this is the first report of this dual mutation pattern in multidrug-resistant influenza a(h3n ...201021041923
[analysis of the situation of swine influenza in the districts upper bavaria, swabia, freiburg and tübingen based on antibody profiles of piglets from bavarian breeding farms].a total of 1026 serum samples from 388 pigs from three bavarian rearing farms in the region of swabia were investigated in the course of investigations into the development of antibodies against influenza a virus subtypes h1n1, h1n2 and h3n2 by haemagglutination inhibition test during the period from november 2002 to february 2004. there were no signs of respiratory disease during this period. the antibody titres decreased steadily in this period which corresponds to the kinetics of maternally-d ...201021043147
in vitro and in vivo anti-influenza virus activity of diarylheptanoids isolated from alpinia officinarum.diarylheptanoids (ao-0002 [7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-4e-hepten-3-one] and ao-0011 [(5s)-5-hydroxy-7-(4''-hydroxyphenyl)-1-phenyl-3-heptanone]) isolated from alpinia officinarum have been reported to exhibit anti-influenza virus activity in vitro. hence, efficacies against influenza virus infection and the mode of antiviral action were evaluated in vivo and in vitro, respectively.201021045258
in vitro assessment of attachment pattern and replication efficiency of h5n1 influenza a viruses with altered receptor specificity.the continuous circulation of the highly pathogenic avian influenza (hpai) h5n1 virus has been a cause of great concern. the possibility of this virus acquiring specificity for the human influenza a virus receptor, alpha2,6-linked sialic acids (sa), and being able to transmit efficiently among humans is a constant threat to human health. different studies have described amino acid substitutions in hemagglutinin (ha) of clinical hpai h5n1 isolates or that were introduced experimentally that resul ...201020392847
epidemiologic study of human influenza virus infection in south korea from 1999 to 2007: origin and evolution of a/fujian/411/2002-like strains.influenza epidemics arise through the accumulation of viral genetic changes, culminating in a novel antigenic type that is able to escape host immunity. following an outbreak of the a/fujian/411/2002-like strains in asia, including china, japan, and south korea, in 2002, australia and new zealand experienced substantial outbreaks of the same strains in 2003, and subsequently worldwide outbreaks occurred in the 2003-2004 season. the emergence of a/fujian/411/2002-like strains coincided with a hig ...201020392920
the impact of key amino acid substitutions in the hemagglutinin of influenza a (h3n2) viruses on vaccine production and antibody response.influenza h3n2 viruses have recently drifted from a/wisconsin/67/05-like to a/brisbane/10/07-like viruses. the effect of key amino acid substitutions in the hemagglutinin (ha) protein on the replication, antigenicity and immunogenicity of cold-adapted, live attenuated vaccine strains was examined. a/brisbane/10/07 egg isolate contained a unique combination of g186 and p194 which were required for efficient virus growth in madin-darby canine kidney (mdck) cells and embryonated chicken eggs, but t ...201020399830
influenza a viral loads in respiratory samples collected from patients infected with pandemic h1n1, seasonal h1n1 and h3n2 viruses.nasopharyngeal aspirate (npa), nasal swab (ns), and throat swab (ts) are common specimens used for diagnosis of respiratory virus infections based on the detection of viral genomes, viral antigens and viral isolation. however, there is no documented data regarding the type of specimen that yields the best result of viral detection. in this study, quantitative real time rt-pcr specific for m gene was used to determine influenza a viral loads present in ns, npa and ts samples collected from patien ...201020403211
antigenic variations of human influenza virus in shiraz, iran.influenza virus is a major cause of human respiratory infections and responsible for pandemics and regional outbreaks around the world. this investigation aims to determine the prevalent influenza genotypes during 2005-2007 outbreaks in shiraz, the capital city of fars province, southern iran and compare the results obtained with those of previous study.201020404455
serologic survey of swine workers for exposure to h2n3 swine influenza a.of the 16 influenza a hemagglutinin (h) subtypes, only h1, h2 and h3 viruses have been shown to cause sustained human infection. whereas h1 and h3 viruses currently circulate seasonally in humans, h2 viruses have not been identified in humans since 1968. in 2006, an h2n3 influenza virus was isolated from ill swine in the united states.201020409213
neuraminidase receptor binding variants of human influenza a(h3n2) viruses resulting from substitution of aspartic acid 151 in the catalytic site: a role in virus attachment?changes in the receptor binding characteristics of human h3n2 viruses have been evident from changes in the agglutination of different red blood cells (rbcs) and the reduced growth capacity of recently isolated viruses, particularly in embryonated eggs. an additional peculiarity of viruses circulating in 2005 to 2009 has been the poor inhibition of hemagglutination by postinfection ferret antisera for many viruses isolated in mdck cells, including homologous reference viruses. this was shown not ...201020410266
quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza a virus.seasonal and pandemic influenza a virus (iav) continues to be a public health threat. however, we lack a detailed and quantitative understanding of the immune response kinetics to iav infection and which biological parameters most strongly influence infection outcomes. to address these issues, we use modeling approaches combined with experimental data to quantitatively investigate the innate and adaptive immune responses to primary iav infection. mathematical models were developed to describe th ...201020410284
an epidemiological modeling and data integration framework.in this work, a cellular automaton software package for simulating different infectious diseases, storing the simulation results in a data warehouse system and analyzing the obtained results to generate prediction models as well as contingency plans, is proposed. the brisbane h3n2 flu virus, which has been spreading during the winter season 2009, was used for simulation in the federal state of tyrol, austria.201020411210
replication, pathogenesis and transmission of pandemic (h1n1) 2009 virus in non-immune pigs.the declaration of the human influenza a pandemic (h1n1) 2009 (h1n1/09) raised important questions, including origin and host range [1], [2]. two of the three pandemics in the last century resulted in the spread of virus to pigs (h1n1, 1918; h3n2, 1968) with subsequent independent establishment and evolution within swine worldwide [3]. a key public and veterinary health consideration in the context of the evolving pandemic is whether the h1n1/09 virus could become established in pig populations ...201020140096
single assay for simultaneous detection and differential identification of human and avian influenza virus types, subtypes, and emergent variants.for more than four decades the cause of most type a influenza virus infections of humans has been attributed to only two viral subtypes, a/h1n1 or a/h3n2. in contrast, avian and other vertebrate species are a reservoir of type a influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus str ...201020140251
influenza viruses differ in ability to infect macrophages and to induce a local inflammatory response following intraperitoneal injection of mice.strains of influenza a virus show marked differences in their ability to infect murine macrophages (mphi) such that strain a/pr/8/34 (pr8; h1n1) infects mphi poorly while strain bjx109 (h3n2) infects mphi to high levels. given the central role of mphi in initiating and regulating inflammatory responses, we hypothesized that virus strains that infect mphi poorly may also be poor at initiating inflammatory responses. studies to compare the inflammatory response of mice after intranasal inoculation ...201020142836
effect of inactivation method on the cross-protective immunity induced by whole 'killed' influenza a viruses and commercial vaccine preparations.we have recently shown that intranasal (i.n.) administration of gamma-irradiated a/pr/8 [a/puerto rico/8/34 (h1n1)] protects mice against lethal avian influenza a/vietnam/1203/2004 (h5n1) and other heterosubtypic influenza a infections. here, we used gamma-irradiated, formalin- and uv-inactivated a/pc [a/port chalmers/1/73 (h3n2)] virus preparations and compared their ability to induce both homologous and heterosubtypic protective immunity. our data show that, in contrast to i.n. vaccination wit ...201020147516
public hospital-based laboratory experience during an outbreak of pandemic influenza a (h1n1) virus infections.the experience of a public hospital virology laboratory during a springtime 2009 outbreak of a novel influenza a (h1n1) virus in new york state is described. influenza virus was isolated from 145 of 613 respiratory swab specimens. symptoms of fever (temperature, 102.7 +/- 0.32 degrees f), cough, upper respiratory infection, myalgia, and headache were reported. atypical symptoms of nausea/vomiting and diarrhea were also observed. illness occurred mainly in patients <or=21 years of age (85/145 pat ...201020147645
highly conserved sequences for human neutralization epitope on hemagglutinin of influenza a viruses h3n2, h1n1 and h5n1: implication for human monoclonal antibody recognition.the epitope sequences within the hemagglutinin (ha) of influenza a virus h3n2 at amino acid residues 173-181 and 227-239 that forms anti-parallel beta-sheet structure are similarly recognized by human monoclonal antibodies (humabs), b-1 and d-1 that we recently obtained using the peripheral blood lymphocytes from two influenza-vaccinated volunteers. both humabs showed strong global neutralization of h3n2 strains. here we show the significant conservation of the beta-sheet region consisting of th ...201020152806
[design and construction of the platform for comparative genomics].to design a versatile genome comparison and visualization platform based on browser/server mode supported by a local server.201020159684
development and comparison of molecular assays for the rapid detection of the pandemic influenza a (h1n1) 2009 virus.human infection with the novel pandemic influenza a (h1n1) virus was first identified in april 2009. two months later, the world health organization (who) had raised the pandemic level to phase 6. rapid case identification is essential for prompt patient management and public health actions. this study developed real-time and conventional reverse transcription-polymerase chain reaction (rrt-pcr and crt-pcr) assays for pandemic h1n1 detection, and compared their sensitivities with protocols devel ...201020166184
influenza in the tropics.data on influenza in tropical countries remain scarce compared with that in temperate countries. however, the emergence of avian influenza virus (h5n1) and the 2009 pandemic represented a major stimulus for advances in knowledge about influenza in many of these countries. this review summarizes recent data on viral and epidemiologic aspects of the condition in tropical countries.201020644472
influenza virus infections among a sample of hospital attendees in ragama, sri lanka.this study was carried out to define the types of influenza viruses circulating among humans and to understand the seasonality of influenza virus activity. such information is essential for deciding on influenza vaccination strategy and on the appropriate time for delivering influenza vaccination, if such a vaccination policy was decided to be a priority.201020645542
prevalence of antibodies to swine influenza viruses in humans with occupational exposure to pigs, thuringia, germany, 2008-2009.the eurasian lineages of swine influenza viruses are different genetically from classical swine h1n1 influenza viruses and comprise avian-like h1n1 and human-like h1n2 and h3n2 subtypes. although sporadic isolation of such viruses from human specimens has been reported, the prevalence of human infections is not known. in the present study, the seroprevalence against eurasian swine influenza viruses was investigated. sera were collected in thuringia, germany, from december 2007 to april 2009. the ...201020648619
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