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a prospective study of romanian agriculture workers for zoonotic influenza infections.in this prospective study we sought to examine seroepidemiological evidence for acute zoonotic influenza virus infection among romanian agricultural workers.201424869796
influenza a virus and tlr7 activation potentiate nox2 oxidase-dependent ros production in macrophages.influenza a virus infects resident alveolar macrophages in the respiratory tract resulting in toll like receptor 7 (tlr7) activation that triggers an inflammatory response to resolve the infection. macrophages are also major sources of reactive oxygen species (ros) via the nox2-containing nadph oxidase. although ros are crucial for pathogen clearance, in response to influenza a virus, ros are touted as being culprit mediators of the lung tissue injury. the aim of the present study was to determi ...201424869957
influenza virus pb1 and neuraminidase gene segments can cosegregate during vaccine reassortment driven by interactions in the pb1 coding region.egg-grown influenza vaccine yields are maximized by infection with a seed virus produced by "classical reassortment" of a seasonal isolate with a highly egg-adapted strain. seed viruses are selected based on a high-growth phenotype and the presence of the seasonal hemagglutinin (ha) and neuraminidase (na) surface antigens. retrospective analysis of h3n2 vaccine seed viruses indicated that, unlike other internal proteins that were predominantly derived from the high-growth parent a/puerto rico/8/ ...201424872588
activation of c-jun n-terminal kinase upon influenza a virus (iav) infection is independent of pathogen-related receptors but dependent on amino acid sequence variations of iav ns1.a hallmark cell response to influenza a virus (iav) infections is the phosphorylation and activation of c-jun n-terminal kinase (jnk). however, so far it is not fully clear which molecules are involved in the activation of jnk upon iav infection. here, we report that the transfection of influenza viral-rna induces jnk in a retinoic acid-inducible gene i (rig-i)-dependent manner. however, neither rig-i-like receptors nor myd88-dependent toll-like receptors were found to be involved in the activat ...201424872593
[monitoring of activity of influenza in santa fe, argentina, 2005-2010].influenza viruses have a relevant public health impact.201424878901
isolation and identification of phase i metabolites of phillyrin in rats.phillyrin was one of the main chemical constituents of the fruit of forsythia suspensa (thunb.) vahl. it showed various bioactivities including antioxidant and anti-inflammatory activities. however, the metabolism of phillyrin remained unknown. this report described the isolation and identification of phase i metabolites of phillyrin in rats. nine metabolites including six new ones were isolated by various column chromatographies and high-performance liquid chromatography. their structures were ...201424879901
detection of avian influenza a/h7n9/2013 virus by real-time reverse transcription-polymerase chain reaction.the first case of avian influenza a/h7n9 infection was reported in shanghai in mid-february, 2013; by may 1, 2013, it had infected 127 people and caused 26 deaths in 10 provinces in china. therefore, it is important to obtain reliable epidemiological data on the spread of this new infectious agent, a need that may be best met by the development of novel molecular methods. here, a new method was described for the detection of avian influenza a/h7n9 using real-time reverse transcription-polymerase ...201424880072
influenza virus h1n1 inhibition by serine protease inhibitor (serpin) antithrombin iii.endogenous serine protease inhibitors (serpins) are anti-inflammatory mediators with multiple biologic functions. serpins are also part of the early innate immune response to viral infection that includes mannose binding lectins, soluble cd14, defensins and antimicrobial peptides. recently, serpin antithrombin iii (atiii) was shown to have broad-spectrum antiviral activity against hiv, hsv and hcv. we tested atiii's antiviral activity against a variety of influenza virus strains. in our studies ...201424883334
a brief introduction to influenza a virus in swine.influenza a viruses (iav) of the orthomyxoviridae virus family cause one of the most important respiratory diseases in pigs as well as humans. repeated outbreaks and rapid spread of genetically and antigenically distinct iavs represent a considerable challenge for animal production and public health. this overlap between human and animal health is a prime example of the "one health" concept. although only subtypes of h1n1, h1n2, and h3n2 are endemic in swine around the world, considerable divers ...201424899434
design, synthesis, antiviral and cytostatic activity of ω-(1h-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues.the efficient synthesis of a new series of polyhydroxylated dibenzyl ω-(1h-1,2,3-triazol-1-yl)alkylphosphonates as acyclic nucleotide analogues is described starting from dibenzyl ω-azido(polyhydroxy)alkylphosphonates and selected alkynes under microwave irradiation. selected o,o-dibenzylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. all compounds were evaluated in vitro for activity against a broad variety of dna and rna viruses and for cytostatic activity ...201424906510
molecular epidemiology and evolution of a(h1n1)pdm09 and h3n2 virus during winter 2012-2013 in beijing, china.in order to evaluate the epidemiology of influenza a and its surface antigens (haemagglutinin [ha] and neuraminidase [na]) for molecular epidemiology and evolution analysis during winter 2012-2013 in beijing, china, we worked within the framework of the chinese national influenza center and collected nasal swabs of patients presenting with influenza-like illness. we found that both a(h1n1)pdm09 (46.8%) and h3n2 (53.2%) viruses were the predominant strains during the 2012-2013 influenza epidemic. ...201424911284
serological and molecular prevalence of swine influenza virus on farms in northwestern mexico.the aim of this study was to provide an overview of the epidemiological status of swine influenza viruses in pigs from northwestern mexico in 2008-2009. a serological and molecular survey was conducted in 150 pigs from 15 commercial farms in sonora, mexico (northwestern region of mexico). the serological data showed that 55% of the sera were positive for the h1n1 subtype, 59% for the h3n2 subtype, and 38% for both subtypes. overall, 16.6% (25/150) of the samples were positive for type a influenz ...201424925324
identification and genetic characterization of avian-origin h3n2 canine influenza viruses isolated from the liaoning province of china in 2012.a total of 158 serum samples and 510 nasal swab specimens were collected between september 2010 and may 2012, from dogs exhibiting respiratory symptoms, in order to investigate the epidemiology of h3n2 canine influenza viruses (civs) in the liaoning province of china. serological surveillance demonstrated that 10.8 % (17/158) of serum samples were positive for h3n2 canine influenza. two h3n2 influenza viruses, a/canine/liaoning/27/2012 and a/canine/liaoning/h6/2012, were isolated from pet dogs i ...201424928168
a packaged paper fluidic-based microdevice for detecting gene expression of influenza a virus.pathotyping and subtyping of influenza a virus were performed with a packaged paper fluidic-based analytical microdevice (pfam) after one-step reverse transcription-polymerase chain reaction (rt-pcr). the pfam contains two test lines: one for detecting m gene to identify the influenza a virus and another for haemagglutinin subtyping to determine the viral strain among h1n1, h3n2, and h5n1. the m gene and the haemagglutinin gene (h1, h3, and h5 genes) were amplified by using the digoxigenin and t ...201424949821
significant cross reactive antibodies to influenza virus in adults and children during a period of marked antigenic drift.little is known about the development of cross-reactive antibodies following natural exposure to pathogens. such knowledge is critical in the development of new universal influenza vaccines.201424950742
conservation of t cell epitopes between seasonal influenza viruses and the novel influenza a h7n9 virus.a novel avian influenza a (h7n9) virus recently emerged in the yangtze river delta and caused diseases, often severe, in over 130 people. this h7n9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as h5n1 and h9n2. while there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved t-cell epitopes between endemic h1n1 and h3n2 influenza viruses and the ...201424950786
characterization of drug-resistant influenza virus a(h1n1) and a(h3n2) variants selected in vitro with laninamivir.neuraminidase inhibitors (nais) play a major role for managing influenza virus infections. the widespread oseltamivir resistance among 2007-2008 seasonal a(h1n1) viruses and community outbreaks of oseltamivir-resistant a(h1n1)pdm09 strains highlights the need for additional anti-influenza virus agents. laninamivir is a novel long-lasting nai that has demonstrated in vitro activity against influenza a and b viruses, and its prodrug (laninamivir octanoate) is in phase ii clinical trials in the uni ...201424957832
epidemiology of influenza virus types and subtypes in south africa, 2009-2012.to determine clinical and epidemiologic differences between influenza caused by different virus types and subtypes, we identified patients and tested specimens. patients were children and adults hospitalized with confirmed influenza and severe acute respiratory illness (sari) identified through active, prospective, hospital-based surveillance from 2009-2012 in south africa. respiratory specimens were tested, typed, and subtyped for influenza virus by pcr. of 16,005 sari patients tested, 1,239 (8 ...201424960314
serological report of pandemic and seasonal human influenza virus infection in dogs in southern china.from january to july 2012, we looked for evidence of subclinical a (h1n1) pdm09 and seasonal human influenza viruses infections in healthy dogs in china. sera from a total of 1920 dogs were collected from guangdong, guangxi, fujian and jiangxi provinces. we also examined archived sera from 66 dogs and cats that were collected during 2008 from these provinces. using hemagglutination inhibition (hi) and microneutralization (mn) assays, we found that only the dogs sampled in 2012 had elevated antib ...201424965232
introductions and evolution of human-origin seasonal influenza a viruses in multinational swine populations.the capacity of influenza a viruses to cross species barriers presents a continual threat to human and animal health. knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. we sequenced the genomes of 141 influenza viruses collected from north american swine during 2002 to 2011 and identified a swine virus that possessed all eight genome segments of human seasonal a/h3n2 virus origin. a molecular clock analysi ...201424965467
higher vaccine effectiveness in seasons with predominant circulation of seasonal influenza a(h1n1) than in a(h3n2) seasons: test-negative case-control studies using surveillance data, spain, 2003-2011.we used data provided by the spanish influenza surveillance system to measure seasonal influenza vaccine effectiveness (ve) against medically attended cases, laboratory confirmed with the predominately circulating influenza virus over eight seasons (2003-2011).201424968153
influenza vaccination accelerates recovery of ferrets from lymphopenia.ferrets are a useful animal model for human influenza virus infections, since they closely mimic the pathogenesis of influenza viruses observed in humans. however, a lack of reagents, especially for flow cytometry of immune cell subsets, has limited research in this model. here we use a panel of primarily species cross-reactive antibodies to identify ferret t cells, cytotoxic t lymphocytes (ctl), b cells, and granulocytes in peripheral blood. following infection with seasonal h3n2 or h1n1pdm09 i ...201424968319
surveillance of influenza virus during 2010-2012 in changsha, china.the objective of this study was to examine the circulating influenza viruses in changsha, china, during 2010-2012. nasopharyngeal specimens were collected from persons with influenza-like illness (ili) who presented for care at two hospitals. of 2,955 patients tested, 278/(9.4%) were positive for influenza virus: 116/(41.7%) were influenza type a(h3n2), 79/(28.4%) were type a(h1n1) pandemic 2009 (pdm09) and 83/(29.9%) were influenza type b. the rates of virus detection varied by age and sex. the ...201424968671
universal immunity to influenza must outwit immune evasion.although an influenza vaccine has been available for 70 years, influenza virus still causes seasonal epidemics and worldwide pandemics. currently available vaccines elicit strain-specific antibody (ab) responses to the surface haemagglutinin (ha) and neuraminidase (na) proteins, but these can be ineffective against serologically-distinct viral variants and novel subtypes. thus, there is a great need for cross-protective or "universal" influenza vaccines to overcome the necessity for annual immun ...201424971078
estimates of mortality attributable to influenza and rsv in the united states during 1997-2009 by influenza type or subtype, age, cause of death, and risk status.influenza and respiratory syncytial virus (rsv) cause substantial mortality from respiratory and other causes in the usa, especially among people aged 65 and older.201424975705
performance characteristics of qualified cell lines for isolation and propagation of influenza viruses for vaccine manufacturing.cell culture is now available as a method for the production of influenza vaccines in addition to eggs. in accordance with currently accepted practice, viruses recommended as candidates for vaccine manufacture are isolated and propagated exclusively in hens' eggs prior to distribution to manufacturers. candidate vaccine viruses isolated in cell culture are not available to support vaccine manufacturing in mammalian cell bioreactors so egg-derived viruses have to be used. recently influenza a (h3 ...201424975811
h3n2 canine influenza virus with the matrix gene from the pandemic a/h1n1 virus: infection dynamics in dogs and ferrets.after an outbreak of pandemic influenza a/h1n1 (ph1n1) virus, we had previously reported the emergence of a recombinant canine influenza virus (civ) between the ph1n1 virus and the classic h3n2 civ. our ongoing routine surveillance isolated another reassortant h3n2 civ carrying the matrix gene of the ph1n1 virus from 2012. the infection dynamics of this h3n2 civ variant (civ/h3n2mv) were investigated in dogs and ferrets via experimental infection and transmission. the civ/h3n2mv-infected dogs an ...201524977303
alzheimer's associated β-amyloid protein inhibits influenza a virus and modulates viral interactions with phagocytes.accumulation of β-amyloid (βa) is a key pathogenetic factor in alzheimer's disease; however, the normal function of βa is unknown. recent studies have shown that βa can inhibit growth of bacteria and fungi. in this paper we show that βa also inhibits replication of seasonal and pandemic strains of h3n2 and h1n1 influenza a virus (iav) in vitro. the 42 amino acid fragment of βa (βa42) had greater activity than the 40 amino acid fragment. direct incubation of the virus with βa42 was needed to achi ...201424988208
evaluation of alere i influenza a&b for rapid detection of influenza viruses a and b.rapid and accurate diagnosis of influenza is important for infection control, as well as for patient management. alere i influenza a&b is an isothermal nucleic acid amplification-based integrated system for detection and differentiation of influenza virus a and influenza virus b. the performance of the alere i influenza a&b was screened using frozen nasopharyngeal-swab specimens collected in viral transport medium (vtm) that were originally tested fresh with the filmarray respiratory panel (rp) ...201424989611
recent h3n2 influenza virus clinical isolates rapidly acquire hemagglutinin or neuraminidase mutations when propagated for antigenic analyses.prior to serological testing, influenza viruses are typically propagated in eggs or cell culture. recent human h3n2 strains bind to cells with low avidity. here, we isolated nine primary h3n2 viral isolates from respiratory secretions of children. upon propagation in vitro, five of these isolates acquired hemagglutinin or neuraminidase mutations that increased virus binding to cell surfaces. these mutations can potentially confound serological assays commonly used to identify antigenically novel ...201424991002
simflu: a simulation tool for predicting the variation pattern of influenza a virus.since the first pandemic outbreak of avian influenza a virus (h5n1 subtype) in 1997, the national center for biotechnology information (ncbi) has provided a large number of influenza virus sequences with well-organized annotations. using the time-series sequences of influenza a viruses, we developed a simulation tool for influenza virus, named simflu, to predict possible future variants of influenza viruses. simflu can create variants from a seed nucleotide sequence of influenza a virus using th ...201424995426
intranasal chitosan-dna vaccines that protect across influenza virus subtypes.an egg-free and broadly effective influenza vaccine that can be produced rapidly, adequately and cost-effectively is needed. in this study, chitosan-associated dnas prepared at various nitrogen/phosphate charge (n/p) ratios were studied for their physicochemical properties, stability, cytotoxicity, and protein expression ability. the chitosan-dna complexes (chitoplexes) of the n/p ratio 2 had the required characteristics including optimal size range, positive surface charge, high dna association ...201424998507
viral etiology and seasonality of influenza-like illness in gabon, march 2010 to june 2011.surveillance of influenza-like illness (ili) in central africa began only recently, and few data are therefore available on the circulation of influenza virus and other respiratory viruses. in gabon, a central african country, we established a surveillance network in four major towns in order to analyze cases of ili among patients who visited health centers between march 2010 and june 2011, and to determine the viral etiology.201425000832
glycan based detection and drug susceptibility of influenza virus.we have developed a panel of synthetic glycans as receptor mimics for the specific capture of influenza viruses. the glycans were printed onto commercial glass slides using a free amine at the end of a spacer to generate a small focused microarray. the microarray was evaluated for its ability to capture three different strains of influenza a virus, two h1n1, a/brisbane/59/2007 and a/solomon islands/3/2006 and one h3n2, a/aichi/2/1968. we observed an excellent detection ability with some compound ...201425007351
expansion of genotypic diversity and establishment of 2009 h1n1 pandemic-origin internal genes in pigs in china.two-way transmission of influenza viruses between humans and swine has been frequently observed, and the occurrence of the 2009 h1n1 pandemic influenza virus (pdm/09) demonstrated that swine-origin viruses could facilitate the genesis of a pandemic strain. although multiple introductions to and reassortment in swine of the pdm/09 virus have been repeatedly reported in both eurasia and the americas, its long-term impact on the development of swine influenza viruses (sivs) has not been systematica ...201425008935
[an international collaborative study on influenza viruses antibody titers and contact patterns of individuals in rural and urban household of guangzhou].to describe the influenza viruses antibody levels and contact patterns of individuals in rural and urban regions of guangzhou and to understand how contact patterns and other factors would correlate with the levels on the titers of antibody.201425009036
influenza and other respiratory viruses involved in severe acute respiratory disease in northern italy during the pandemic and postpandemic period (2009-2011).since 2009 pandemic, international health authorities recommended monitoring severe and complicated cases of respiratory disease, that is, severe acute respiratory infection (sari) and acute respiratory distress syndrome (ards). we evaluated the proportion of sari/ards cases and deaths due to influenza a(h1n1)pdm09 infection and the impact of other respiratory viruses during pandemic and postpandemic period (2009-2011) in northern italy; additionally we searched for unknown viruses in those case ...201425013770
effectiveness of trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the united kingdom: 2012/13 end of season results.the effectiveness of the 2012/13 trivalent seasonal influenza vaccine (tiv) was assessed using a test-negative case-control study of patients consulting primary care with influenza-like illness in the united kingdom. strain characterisation was undertaken on selected isolates. vaccine effectiveness (ve) against confirmed influenza a(h3n2), a(h1n1) and b virus infection, adjusted for age, sex, surveillance scheme (i.e. setting) and month of sample collection was 26% (95% confidence interval (ci): ...201425033051
use of fractional factorial design to study the compatibility of viral ribonucleoprotein gene segments of human h7n9 virus and circulating human influenza subtypes.avian h7n9 influenza viruses may pose a further threat to humans by reassortment with human viruses, which could lead to generation of novel reassortants with enhanced polymerase activity. we previously established a novel statistical approach to study the polymerase activity of reassorted vrnps (influenza other respir viruses. 2013;7:969-78). here, we report the use of this method to study recombinant vrnps with subunits derived from human h1n1, h3n2, and h7n9 viruses. our results demonstrate t ...201425043276
divergent immune responses and disease outcomes in piglets immunized with inactivated and attenuated h3n2 swine influenza vaccines in the presence of maternally-derived antibodies.live-attenuated influenza virus (laiv) prime-boost vaccination previously conferred protection against heterologous h3n2 swine influenza challenge, including in piglets with maternally derived antibodies (mda). conversely, a whole-inactivated virus (wiv) vaccine was associated with enhanced disease. this study was aimed at identifying immune correlates of cross-protection. piglets with and without mda received intramuscular adjuvanted wiv or intranasal laiv, and were challenged with heterologous ...201425043588
global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012-2013.emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (nais) is sporadic, often follows exposure to nais, but occasionally occurs in the absence of nai pressure. the emergence and global spread in 2007/2008 of a(h1n1) influenza viruses showing clinical resistance to oseltamivir due to neuraminidase (na) h275y substitution, in the absence of drug pressure, warrants continued vigilance and monitoring for similar viruses. four world health organization (who) collabo ...201425043638
azapropellanes with anti-influenza a virus activity.the synthesis of several [4,4,3], [4,3,3], and [3,3,3]azapropellanes is reported. several of the novel amines displayed low-micromolar activities against an amantadine-resistant h1n1 strain, but they did not show activity against an amantadine-sensitive h3n2 strain. none of the tested compounds inhibit the influenza a/m2 proton channel function. most of the compounds did not show cytotoxicity for mdck cells.201425050174
targeting the ha2 subunit of influenza a virus hemagglutinin via cd40l provides universal protection against diverse subtypes.the influenza viral hemagglutinin (ha) is comprised of two subunits. current influenza vaccine predominantly induces neutralizing antibodies (abs) against the ha1 subunit, which is constantly evolving in unpredictable fashion. the other subunit, ha2, however, is highly conserved but largely shielded by the ha head domain. thus, enhancing immune response against ha2 could potentially elicit broadly inhibitory abs. we generated a recombinant adenovirus (rad) encoding secreted fusion protein, consi ...201525052763
neuraminidase gene homology contributes to the protective activity of influenza vaccines prepared from the influenza virus library.whole-virus (wv) vaccines from influenza a/duck/hokkaido/77 (h3n2), and its reassortant strains h3n4, h3n5 and h3n7, which have the same haemagglutinin (ha) gene but different neuraminidase (na) genes, were prepared from our influenza virus library. mice were intranasally immunized with equivalent doses of each vaccine (1-0.01 µg per mouse). all of the mice that received the highest dose of each vaccine (1 µg per mouse) showed equivalent high ha-inhibiting (hi) antibody titres and survived the h ...201425053564
genomic reassortants of pandemic a (h1n1) 2009 virus and endemic porcine h1 and h3 viruses in swine in japan.from 2010 to 2013 in japan, we isolated 11 swine influenza viruses (sivs) from pigs showing respiratory symptoms. sequence and phylogenetic analyses showed that 6 h1n1 viruses originated from the pandemic (h1n1) 2009 (pdm 09) virus and the other 5 viruses were reassortants between sivs and pdm 09 viruses, representing 4 genotypes. two h1n2 viruses contained h1 and n2 genes originated from japanese h1n2 siv together with internal genes of pdm 09 viruses. additionally, 1 h1n2 virus contained a fur ...201425056678
chimeric influenza-virus-like particles containing the porcine reproductive and respiratory syndrome virus gp5 protein and the influenza virus ha and m1 proteins.both porcine reproductive and respiratory syndrome and swine influenza are acute, highly contagious swine diseases. these diseases pose severe threats for the swine industry and cause heavy economic losses worldwide. in this study, we have developed a chimeric virus-like particle (vlp) vaccine candidate for porcine reproductive and respiratory syndrome virus (prrsv) and h3n2 influenza virus and investigated its immunogenicity in mice. the ha and m1 proteins from the h3n2 influenza virus and the ...201425064513
an h1-h3 chimeric influenza virosome confers complete protection against lethal challenge with pr8 (h1n1) and x47 (h3n2) viruses in mice.annual health threats and economic damages caused by influenza virus are still a main concern of the world health organization and other health departments all over the world. an influenza virosome is a highly efficient immunomodulating carrier mimicking the natural antigen presentation pathway and has shown an excellent tolerability profile due to its biocompatibility and purity. the major purpose of this study was to construct a new chimeric virosome influenza vaccine containing hemagglutinin ...201425066138
[the peculiarities of the influenza epidemics in some areas of russia during 2012-2013 season. the influenza a (h1n1) pdm09 virus domination in european countries].the peculiarities of the influenza viruses circulation in 2012-2013 are discussed. the results were obtained in 10 cities of russia, where basic laboratories of the influenza ecology and epidemics center of on the basis of ivanovsky institute of virology, ministry of health of the russian federation, are situated. the increasing rate of the ard morbidity caused by influenza viruses was observed in january-march 2013. the highest indices of the morbidity were detected during 6-7 weeks with the fo ...201625069278
detection of h3n2 canine influenza virus using a quartz crystal microbalance.label-free technology-based quartz crystal microbalance (qcm) is an emerging tool in biological research. in this study, qcm was applied successfully for the rapid diagnosis of h3n2 canine influenza virus (civ) infection. prolinker™ b, a calixcrown derivative, enables antibodies to be attached to a gold-coated quartz surface and positioned in a regular pattern with the correct orientation. the prolinker-coated quartz-based assay detected h3n2 civ at lower concentrations (2(2) ha unit) than a com ...201425072379
[evaluation of the sensitivity of a densitometry system, in judging the result of influenza virus antigen-detection kit using immunochromatography].immunochromatography viral antigen-detection kits have become popular in clinical settings in japan. influenza virus detection kit is one of them. it is sometimes used in early phase of the disease, combined with the early treatment with anti-influenza drugs. most of them are invented to visually read the test line on their kits. however, we should be careful about their reliability of them. sometimes human errors occur at the visual tests, and they have different sensitivities among the kits fr ...201425073199
antiviral activity of baicalin against influenza a (h1n1/h3n2) virus in cell culture and in mice and its inhibition of neuraminidase.scutellaria baicalensis georgi, a chinese herbal decoction, has been used for the treatment of the common cold, fever and influenza virus infections. in previous studies, we found that oral administration of baicalein resulted in the inhibition of influenza a virus replication in vivo, which was linked to baicalin in serum. however, the effective dose and underlying mechanisms of the efficacy of baicalin against influenza a virus have not been fully elucidated. in this study, the antiviral effec ...201425078390
evaluation of the temporal association between kawasaki disease and viral infections in south korea.this study is aimed at elucidating potential temporal associations between the occurrence of kawasaki disease (kd) and various viral infections.201425089137
influenza vaccine effectiveness against medically-attended influenza illness during the 2012-2013 season in beijing, china.influenza vaccine coverage remains low in china, and there is limited information on the preventive value of local vaccination programs.201425092635
the effectiveness of influenza vaccination in preventing hospitalizations in children in hong kong, 2009-2013.influenza vaccination is widely recommended every year to protect individuals against influenza virus infection and illness. there are few published estimates of influenza vaccine effectiveness against hospitalization in children or from subtropical regions.201425092636
inhibitory potency of flavonoid derivatives on influenza virus neuraminidase.the constant risk of emerging new influenza virus strains that are resistant to established inhibitors like oseltamivir leaves influenza neuraminidase (na) a prominent target for drug design. the inhibitory activity of several flavonoid derivatives was experimentally tested in comparison to oseltamivir for the na expressed by the seasonal influenza virus strains a/california/7/09 (a(h1n1)pdm09), a/perth/16/09 (a(h3n2)), and b/brisbane/60/08. ic50 values of polyphenols confirmed moderate inhibiti ...201425096296
induction of cd8 t cell heterologous protection by a single dose of single-cycle infectious influenza virus.the effector functions of specific cd8 t cells are crucial in mediating influenza heterologous protection. however, new approaches for influenza vaccines that can trigger effective cd8 t cell responses have not been extensively explored. we report here the generation of single-cycle infectious influenza virus that lacks a functional hemagglutinin (ha) gene on an x31 genetic background and demonstrate its potential for triggering protective cd8 t cell immunity against heterologous influenza virus ...201425100831
pi3k/akt signaling pathway modulates influenza virus induced mouse alveolar macrophage polarization to m1/m2b.macrophages polarized to m1 (pro-inflammation) or m2 (anti-inflammation) phenotypes in response to environmental signals. in this study, we examined the polarization of alveolar macrophage (am), following induction by different influenza virus strains (st169 (h1n1), st602 (h3n2) and hkg9 (h9n2)). macrophages from other tissues or cell line exert alternative responding pattern, and am is necessary for investigating the respiratory system. am polarized toward the m1 phenotype after 4 hours of infe ...201425105760
evolution of oseltamivir resistance mutations in influenza a(h1n1) and a(h3n2) viruses during selection in experimentally infected mice.the evolution of oseltamivir resistance mutations during selection through serial passages in animals is still poorly described. herein, we assessed the evolution of neuraminidase (na) and hemagglutinin (ha) genes of influenza a/wsn/33 (h1n1) and a/victoria/3/75 (h3n2) viruses recovered from the lungs of experimentally infected balb/c mice receiving suboptimal doses (0.05 and 1 mg/kg of body weight/day) of oseltamivir over two generations. the traditional phenotypic and genotypic methods as well ...201425114143
[genetic characteristics of influenza a/h3n2 virus neuraminidase gene: a survey from 2010 to 2012 in qinghai province, china].this study aims to perform a survey of genetic variation in neuraminidase (na) gene of influenza a/h3n2 virus, as well as related resistance to na inhibitors, in qinghai province of china, 2010 to 2012. strains of influenza a/h3n2 isolated during an influenza survey from 2010 to 2012 in qinghai were enrolled by random sampling. viral rna was extracted and amplified by rt-pcr. purified pcr products were sequenced thereafter. genetic analysis of nucleic acid and the derived amino acid sequences wa ...201425118381
computational prediction of vaccine strains for human influenza a (h3n2) viruses.human influenza a viruses are rapidly evolving pathogens that cause substantial morbidity and mortality in seasonal epidemics around the globe. to ensure continued protection, the strains used for the production of the seasonal influenza vaccine have to be regularly updated, which involves data collection and analysis by numerous experts worldwide. computer-guided analysis is becoming increasingly important in this problem due to the vast amounts of generated data. we here describe a computation ...201425122778
desc1 and mspl activate influenza a viruses and emerging coronaviruses for host cell entry.the type ii transmembrane serine protease (ttsp) tmprss2 cleaves and activates the influenza virus and coronavirus surface proteins. expression of tmprss2 is essential for the spread and pathogenesis of h1n1 influenza viruses in mice. in contrast, h3n2 viruses are less dependent on tmprss2 for viral amplification, suggesting that these viruses might employ other ttsps for their activation. here, we analyzed ttsps, reported to be expressed in the respiratory system, for the ability to activate in ...201425122802
characterization of variations in pb2, ns1, m, neuraminidase and hemagglutinin of influenza a (h3n2) viruses in iran.in the influenza a viruses, neuraminidase (na), hemagglutinin (ha), pb2, ns1 and m are responsible for the disease pathogenicity. the mechanism of pathogenicity differs among these viruses. binding of host proteases by the viral na, sequence of ha in the cleavage and receptor-binding sites, number of oligosaccharide side chains of ha, shortening of na, and substitutions in pb2, ns1 and m genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses.201425147684
swine-to-human transmission of influenza a(h3n2) virus at agricultural fairs, ohio, usa, 2012.agricultural fairs provide an opportunity for bidirectional transmission of influenza a viruses. we sought to determine influenza a virus activity among swine at fairs in the united states. as part of an ongoing active influenza a virus surveillance project, nasal swab samples were collected from exhibition swine at 40 selected ohio agricultural fairs during 2012. influenza a(h3n2) virus was isolated from swine at 10 of the fairs. according to a concurrent public health investigation, 7 of the 1 ...201425148572
deep sequencing reveals the eight facets of the influenza a/hongkong/1/1968 (h3n2) virus cap-snatching process.the influenza a virus rna polymerase cleaves the 5' end of host pre-mrnas and uses the capped rna fragments as primers for viral mrna synthesis. we performed deep sequencing of the 5' ends of viral mrnas from all genome segments transcribed in both human (a549) and mouse (m-1) cells infected with the influenza a/hongkong/1/1968 (h3n2) virus. in addition to information on rna motifs present, our results indicate that the host primers are divergent between the viral transcripts. we observed differ ...201425154590
cellular and humoral cross-immunity against two h3n2v influenza strains in presumably unexposed healthy and hiv-infected subjects.human cases of infection due to a novel swine-origin variant of influenza a virus subtype h3n2 (h3n2v) have recently been identified in the united states. pre-existing humoral and cellular immunity has been recognized as one of the key factors in limiting the infection burden of an emerging influenza virus strain, contributing to restrict its circulation and to mitigate clinical presentation. aim of this study was to assess humoral and cell-mediated cross immune responses to h3n2v in immuno-comp ...201425162670
live attenuated and inactivated influenza vaccines in children.live attenuated influenza vaccine (laiv) and inactivated influenza vaccine (iiv) are available for children. local and systemic immunity induced by laiv followed a month later by laiv and iiv followed by laiv were investigated with virus recovery after laiv doses as surrogates for protection against influenza on natural exposure.201525165161
cleavage of hemagglutinin-bearing lentiviral pseudotypes and their use in the study of influenza virus persistence.influenza a viruses (iavs) are a major cause of infectious respiratory human diseases and their transmission is dependent upon the environment. however, the role of environmental factors on iav survival outside the host still raises many questions. in this study, we used lentiviral pseudotypes to study the influence of the hemagglutinin protein in iav survival. high-titered and cleaved influenza-based lentiviral pseudoparticles, through the use of a combination of two proteases (hat and tmprss2) ...201425166303
early activation of map kinases by influenza a virus x-31 in murine macrophage cell lines.early molecular responses to influenza a (flua) virus strain a/x-31 h3n2 in macrophages were explored using j774.a1 and raw 264.7 murine cell lines. nf-kappa b (nfκb) was reported to be central to flua host-response in other cell types. our data showed that flua activation of the classical nfκb dependent pathway in these macrophages was minimal. regulator proteins, ikappab-alpha and -beta (iκbα, iκbβ), showed limited degradation peaking at 2 h post flua exposure and p65 was not observed to trans ...201425166426
influenza polymerase encoding mrnas utilize atypical mrna nuclear export.influenza is a segmented negative strand rna virus. each rna segment is encapsulated by influenza nucleoprotein and bound by the viral rna dependent rna polymerase (rdrp) to form viral ribonucleoproteins responsible for rna synthesis in the nucleus of the host cell. influenza transcription results in spliced mrnas (m2 and ns2), intron-containing mrnas (m1 and ns1), and intron-less mrnas (ha, na, np, pb1, pb2, and pa), all of which undergo nuclear export into the cytoplasm for translation. most c ...201425168591
infection of influenza virus neuraminidase-vaccinated mice with homologous influenza virus leads to strong protection against heterologous influenza viruses.vaccination is the best measure to prevent influenza pandemics. here, we studied the protective effect against heterologous influenza viruses, including a/reassortant/nymc x-179a (ph1n1), a/chicken/henan/12/2004 (h5n1), a/chicken/jiangsu/7/2002 (h9n2) and a/guizhou/54/89×a/pr/8/34 (a/guizhou-x) (h3n2), in mice first vaccinated with a dna vaccine of haemagglutinin (ha) or neuraminidase (na) of a/pr/8/34 (pr8) and then infected with the homologous virus. we showed that pr8 ha or na vaccination bot ...201425170051
influenza m2 virus-like particles confer a broader range of cross protection to the strain-specific pre-existing immunity.immunity in humans with annual vaccination does not provide effective protection against antigenically distinct strains. as an approach to improve cross-protection in the presence of pre-existing strain-specific immunity, we investigated the efficacy of heterologous and heterosubtypic protection in previously vaccinated mice at earlier times after subsequent immunization with conserved-antigenic target influenza m2 ectodomain (m2e) virus-like particle vaccine (m2e5× vlp). immunization of mice wi ...201425171841
t-cell-mediated cross-strain protective immunity elicited by prime-boost vaccination with a live attenuated influenza vaccine.antigenic drift and shift of influenza viruses require frequent reformulation of influenza vaccines. in addition, seasonal influenza vaccines are often mismatched to the epidemic influenza strains. this stresses the need for a universal influenza vaccine.201425172265
a population prevalence study on influenza infection in dogs in southern italy.despite several data on influenza infection in dogs, the first natural outbreak of canine influenza virus, closely related to h3n8 equine subtype, dates back to 2004 in florida. subsequent studies highlighted the role of dogs in adaptation of h5n1 to mammals and the susceptibility of dogs to different subtypes of influenza. a prevalence study was carried out on 562 sera collected from pet and kennel dogs in the south of italy. a c-elisa test was employed and c-elisa-positive, c-elisa-doubtful an ...201425180843
an efficient genome sequencing method for equine influenza [h3n8] virus reveals a new polymorphism in the pa-x protein.h3n8 equine influenza virus (eiv) has caused disease outbreaks in horses across the world since its first isolation in 1963. however, unlike human, swine and avian influenza, there is relatively little sequence data available for this virus. the majority of published sequences are for the segment encoding haemagglutinin (ha), one of the two surface glycoproteins, making it difficult to study the evolution of the other gene segments and determine the level of reassortment occurring between sub-li ...201425183201
generation and characterization of influenza a viruses with altered polymerase fidelity.genetic diversity of influenza a viruses (iav) acquired through the error-prone rna-dependent rna polymerase (rdrp) or through genetic reassortment enables perpetuation of iav in humans through epidemics or pandemics. here, to assess the biological significance of genetic diversity acquired through rdrp, we characterize an iav fidelity variant derived from passaging a seasonal h3n2 virus in the presence of ribavirin, a purine analogue that increases guanosine-to-adenosine mutations. we demonstra ...201425183443
severity of clinical disease and pathology in ferrets experimentally infected with influenza viruses is influenced by inoculum volume.ferrets are a valuable model for influenza virus pathogenesis, virus transmission, and antiviral therapy studies. however, the contributions of the volume of inoculum administered and the ferret's respiratory tract anatomy to disease outcome have not been explored. we noted variations in clinical disease outcomes and the volume of inoculum administered and investigated these differences by administering two influenza viruses (a/california/07/2009 [h1n1 pandemic] and a/minnesota/11/2010 [h3n2 var ...201425187553
surveillance for emerging respiratory viruses.several new viral respiratory tract infectious diseases with epidemic potential that threaten global health security have emerged in the past 15 years. in 2003, who issued a worldwide alert for an unknown emerging illness, later named severe acute respiratory syndrome (sars). the disease caused by a novel coronavirus (sars-cov) rapidly spread worldwide, causing more than 8000 cases and 800 deaths in more than 30 countries with a substantial economic impact. since then, we have witnessed the emer ...201425189347
emerging viral respiratory tract infections--environmental risk factors and transmission.the past decade has seen the emergence of several novel viruses that cause respiratory tract infections in human beings, including middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia, an h7n9 influenza a virus in eastern china, a swine-like influenza h3n2 variant virus in the usa, and a human adenovirus 14p1 also in the usa. mers-cov and h7n9 viruses are still a major worldwide public health concern. the pathogenesis and mode of transmission of mers-cov and h7n9 influenza a v ...201425189350
characterization of a broadly neutralizing monoclonal antibody that targets the fusion domain of group 2 influenza a virus hemagglutinin.due to continuous changes to its antigenic regions, influenza viruses can evade immune detection and cause a significant amount of morbidity and mortality around the world. influenza vaccinations can protect against disease but must be annually reformulated to match the current circulating strains. in the development of a broad-spectrum influenza vaccine, the elucidation of conserved epitopes is paramount. to this end, we designed an immunization strategy in mice to boost the humoral response ag ...201425210195
effectiveness of post-exposition prophylaxis with oseltamivir in nursing homes: a randomised controlled trial over four seasons.oseltamivir has been registered for use as post-exposition prophylaxis (pep) following exposure to influenza, based on studies among healthy adults. effectiveness among frail elderly nursing home populations still needs to be properly assessed.201425210532
antiviral activity of novel oseltamivir derivatives against some influenza virus strains.the aim of this study was to investigate the in vitro cytotoxicity of oseltamivir derivatives and determine their activity against a/h1n1/pr/8/34 and a/h3n2/hongkong/8/68 - strains of influenza virus. antiviral activity of these compounds was determined by using two methods. mtt staining was used to assess the viability of mdck cells infected with influenza viruses and treated with various concentrations of drugs. in parallel, the effect of drugs on viral replication was assessed using the hemag ...201425210935
recombinant influenza h7 hemagglutinins induce lower neutralizing antibody titers in mice than do seasonal hemagglutinins.vaccines against avian influenza viruses often require high hemagglutinin (ha) doses or adjuvants to achieve serological titers associated with protection against disease. in particular, viruses of the h7 subtype frequently do not induce strong antibody responses following immunization.201425213778
comparative analysis of virulence of a novel, avian-origin h3n2 canine influenza virus in various host species.a novel avian-origin h3n2 canine influenza a virus (civ) that showed high sequence similarities in hemagglutinin and neuraminidase genes with those of non-pathogenic avian influenza viruses was isolated in our routine surveillance program in south korea. we previously reported that the pathogenicity of this strain could be reproduced in dogs and cats. in the present study, the host tropism of h3n2 civ was examined by experimental inoculation into several host species, including chickens, pigs, m ...201525218482
strain-specific antiviral activity of iminosugars against human influenza a viruses.drugs that target host cell processes can be employed to complement drugs that specifically target viruses, and iminosugar compounds that inhibit host α-glucosidases have been reported to show antiviral activity against multiple viruses. here the effect and mechanism of two iminosugar α-glucosidase inhibitors, n-butyl-deoxynojirimycin (nb-dnj) and n-nonyl-deoxynojirimycin (nn-dnj), on human influenza a viruses was examined.201425223974
identification of genotypes of influenza a virus in malaysia.influenza is considered as an emerging disease until today. the present study was undertaken to determine the prevalent genotypes of influenza a virus in malaysia.201425225528
using multiple linear regression and physicochemical changes of amino acid mutations to predict antigenic variants of influenza a/h3n2 viruses.among human influenza viruses, strain a/h3n2 accounts for over a quarter of a million deaths annually. antigenic variants of these viruses often render current vaccinations ineffective and lead to repeated infections. in this study, a computational model was developed to predict antigenic variants of the a/h3n2 strain. first, 18 critical antigenic amino acids in the hemagglutinin (ha) protein were recognized using a scoring method combining phi (ϕ) coefficient and information entropy. next, a pr ...201425227088
temporal insight into the natural generation of a new reassortant porcine influenza virus in a swine holding.the influenza a virus (iav) subtypes h1n1, h3n2 and h1n2 are the most prevalent subtypes in swine in italy. reassortant influenza a viruses subtypes in swine appeared in european pig population. in particular reassortant viruses carrying genome segment from the pandemic h1n1 (h1n1pdm) are reported in many european countries, including italy. in a 1000 sows farrow-to feeder farm, in northern italy, we isolated 10 iavs from recurrent episodes of respiratory disease in 45-70 days-old pigs from sept ...201425239679
a plasmon-assisted fluoro-immunoassay using gold nanoparticle-decorated carbon nanotubes for monitoring the influenza virus.a plasmon-assisted fluoro-immunoassay (pafi) was developed for the detection of the influenza virus by using au nanoparticle (au np)-decorated carbon nanotubes (aucnts) that were synthesized using phytochemical composites at room temperature in deionized water. specific antibodies (abs) against the influenza virus were conjugated onto the surface of aucnts and cadmium telluride quantum dots (qds), which had a photoluminescence intensity that varied as a function of virus concentration and a dete ...201525240957
in vitro anti-influenza a activity of interferon (ifn)-λ1 combined with ifn-β or oseltamivir carboxylate.influenza viruses, which can cross species barriers and adapt to new hosts, pose a constant potential threat to human health. the influenza pandemic of 2009 highlighted the rapidity with which an influenza virus can spread worldwide. currently available antivirals have a number of limitations against influenza, and novel antiviral strategies, including novel drugs and drug combinations, are urgently needed. here, we evaluated the in vitro effects of interferon (ifn)-β, ifn-λ1, oseltamivir carbox ...201425245230
multiple influenza a (h3n2) mutations conferring resistance to neuraminidase inhibitors in a bone marrow transplant recipient.immunocompromised patients are predisposed to infections caused by influenza virus. influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. this approach may promote the emergence of resistant strains. characterization of neuraminidase (na) inhibitor (nai)-resistant strains of influenza a virus is essential for documenting causes of resistance. in this ...201425246391
enhanced natural killer-cell and t-cell responses to influenza a virus during pregnancy.pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. although some data suggest that natural killer (nk)- and t-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. thus, we analyzed the responses of women that were pregnant (n = 21) versus those that were not (n = 29) immediately before inactivated influenza vaccination (iiv), 7 d after vaccination, and 6 wk postpar ...201425246558
synthesis and influenza virus inhibitory activities of carbosilane dendrimers peripherally functionalized with hemagglutinin-binding peptide.a series of carbosilane dendrimers uniformly functionalized with hemagglutinin (ha) binding peptide (sialic acid-mimic peptide, ala-arg-leu-pro-arg) was systematically synthesized, and their anti-influenza virus activity was evaluated. the carbosilane-based peptide dendrimers, unlike sialylated dendrimers, cannot be digested by virus neuraminidases. the peptide dendrimers exhibited intriguing biological activities depending on the form of their core frame, with a dumbbell-type peptide dendrimer ...201425249262
comparative pathology of pigs infected with korean h1n1, h1n2, or h3n2 swine influenza a viruses.the predominant subtypes of swine influenza a virus (siv) in korea swine population are h1n1, h1n2, and h3n2. the viruses are genetically close to the classical u.s. h1n1 and triple-reassortant h1n2 and h3n2 viruses, respectively. comparative pathogenesis caused by korean h1n1, h1n2, and h3n2 siv was evaluated in this study.201425253051
the association of meningococcal disease with influenza in the united states, 1989-2009.prior influenza infection is a risk factor for invasive meningococcal disease. quantifying the fraction of meningococcal disease attributable to influenza could improve understanding of viral-bacterial interaction and indicate additional health benefits to influenza immunization.201425265409
characterization of uncultivable bat influenza virus using a replicative synthetic virus.bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., ebola, sars-cov). recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. this discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the ha ...201425275541
in vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against clinical isolates of influenza virus in the japanese 2012-2013 season.the neuraminidase inhibitors (nais) oseltamivir phosphate (tamiflu(®)), zanamivir (relenza(®)), laninamivir octanoate (inavir(®)), and peramivir (rapiacta(®)) have been available for the treatment of influenza in japan since 2010. the emergence of resistant virus to any of the nais is a great concern for influenza treatment. to assess the extent of viral resistance, we measured the 50% inhibitory concentration (ic50) of each nai for influenza virus isolates in the 2012-2013 influenza season and ...201525277670
complete genome sequences of h3n2 canine influenza virus with the matrix gene from the pandemic a/h1n1 virus.we analyzed the complete genome sequence containing the 3' and 5' noncoding regions (ncrs) of h3n2 canine influenza virus (civ) with the matrix gene from the pandemic a/h1n1 virus, which will provide a better understanding of the pathogenesis, transmission, and evolution of variant civ.201425278543
relative timing of influenza disease by age group.a detailed understanding of influenza movement in communities during yearly epidemics is needed to inform improved influenza control programs. we sought to determine the relative timing of influenza presentation and symptom onset by age group and influenza strain. prospective, laboratory-confirmed surveillance was performed over three moderate influenza seasons in emergency departments and inpatient settings of both medical centers in winston-salem, nc. influenza disease presented first in schoo ...201425280434
efficacy and safety of treatment with an anti-m2e monoclonal antibody in experimental human influenza.the efficacy of tcn-032, a human monoclonal antibody targeting a conserved epitope on m2e, was explored in experimental human influenza.201525281755
a nonfusogenic antigen mimic of influenza hemagglutinin glycoproteins constituted with soluble full-length ha1 and truncated ha2 proteins expressed in e. coli.a novel method is proposed to produce a soluble recombinant antigen mimic, constituted with full-length ha1 and truncated ha2 individually expressed in e. coli, instead of a precursor form of hemagglutinin protein, that is similar to the naturally processed and disulfide-linked ha1/ha2 on the envelope of the influenza a virus strain x-31 (h3n2). a truncated ectodomain of ha2 subunit, ha2(23-185)/c137s, lacked two membrane-interacting sequences, i.e., the n-terminal fusion peptide as well as the ...201525288022
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