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[monitoring of activity of influenza in santa fe, argentina, 2005-2010].influenza viruses have a relevant public health impact.201424878901
[optimization of culture condition for cultivation of influenza virus a on mdck cell].to optimize the cultivation condition of influenza virus a on mdck cells and to improve the separation rate and the inspected effect of influenza virus.201424868970
safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: a phase i dose escalating study in healthy volunteers.live attenuated influenza vaccine (laiv) offers the promise of inducing a variety of immune responses thereby conferring protection to circulating field strains. laivs are based on cold adapted and temperature sensitive phenotypes of master donor viruses (mdvs) containing the surface glycoprotein genes of seasonal influenza strains. two types of mdv lineages have been described, the ann arbor lineages and the a/leningrad/17 and b/ussr/60 lineages. here the safety and immunogenicity of a madin da ...201424858566
protective efficacy of intranasally administered bivalent live influenza vaccine and immunological mechanisms underlying the protection.previously we reported the generation of a new potential live attenuated influenza vaccine (laiv) named siv/606 that expresses h1 and h3 has. we also demonstrated intratracheal vaccination of siv/606 conferred protection against infections with both h1 and h3 swine influenza virus subtypes in pigs. here we vaccinated pigs with siv/606 intranasally, which is a more suitable route for laiv, and evaluated vaccine efficacy. intranasal vaccination of siv/606 induced serum igg antibody responses again ...201424837774
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 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
effectiveness of seasonal influenza vaccinations against laboratory-confirmed influenza-associated infections among singapore military personnel in 2010-2013.limited information is available about seasonal influenza vaccine effectiveness (ve) in tropical communities.201424828687
influenza virus genotypes circulating in and around lucknow, uttar pradesh, india, during post pandemic period, august 2010--september 2012.during the post influenza pandemic period, continuous surveillance of influenza virus and its subtypes is mandatory to help the policy makers to take effective and appropriate decisions. therefore, this study was planned to determine the pattern of influenza virus activity in context to various meteorological and clinical parameters in and around lucknow, uttar pradesh, india, during post pandemic period august 2010 - september 2012.201424820836
[determination of the frequency of human bocavirus and other respiratory viruses among 0-2 years age group children diagnosed as acute bronchiolitis].acute bronchiolitis, mostly seen in infants and younger children, is a lower respiratory tract infection frequently caused by viral agents. we aimed to determine the frequency of a broad panel of respiratory viruses including human bocavirus (hbov) and to assess the clinical characteristics of acute bronchiolitis in a group of children under 24 months of age. a total of 62 children (45 male, 17 female; age range: 0-2 years) with the initial diagnosis of acute bronchiolitis and 33 healthy childre ...201424819262
comparison of the characteristics of elderly influenza patients in two consecutive seasons.the seasonality of influenza infections can be affected by virus subtypes, climate, and social networking in populations. while these factors are well known, their relative influences in specific age groups have not been fully investigated. during 2010-2011, patients aged 65 years and above with influenza virus infections were recruited from a regional hospital in hong kong. they were either residents of homes for the elderly (n=60) or living with their family (n=75). two seasons were distinguis ...201424815741
suppressor of cytokine signaling 4 (socs4) protects against severe cytokine storm and enhances viral clearance during influenza infection.suppressor of cytokine signaling (socs) proteins are key regulators of innate and adaptive immunity. there is no described biological role for socs4, despite broad expression in the hematopoietic system. we demonstrate that mice lacking functional socs4 protein rapidly succumb to infection with a pathogenic h1n1 influenza virus (pr8) and are hypersusceptible to infection with the less virulent h3n2 (x31) strain. in socs4-deficient animals, this led to substantially greater weight loss, dysregula ...201424809749
bifunctional thiosialosides inhibit influenza virus.we have synthesized a panel of bivalent s-sialoside analogues, with modifications at the 4 position, as inhibitors of influenza virus. these first generation compounds show ic50 values ranging from low micromolar to high nanomolar in enzyme inhibition and plaque reduction assays with two intact viruses, influenza h1n1 (a/california/07/2009) and h3n2 (a/hongkong/8/68).201424374271
genetic and antigenic typing of seasonal influenza virus breakthrough cases from a 2008-2009 vaccine efficacy trial.estimations of the effectiveness of vaccines against seasonal influenza virus are guided by comparisons of the antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in a vaccine. this study examined whether the prediction of antigenicity using a sequence analysis of the hemagglutinin (ha) gene-encoded ha1 domain is a simpler alternative to using the conventional hemagglutination inhibition (hi) assay, which requires influenza virus culturing. spec ...201424371255
influenza associated mortality in southern china, 2010-2012.influenza caused substantial morbidity and mortality worldwide. the mortality burden caused by influenza has been under evaluation; however, data assessing this burden have been relatively sparse in tropical or subtropical regions. we estimated influenza-associated mortality in guangzhou, china and assessed the excess mortality due to different influenza virus subtypes.201424370709
influenza a virus infections in swine: pathogenesis and diagnosis.influenza has been recognized as a respiratory disease in swine since its first appearance concurrent with the 1918 "spanish flu" human pandemic. all influenza viruses of significance in swine are type a, subtype h1n1, h1n2, or h3n2 viruses. influenza viruses infect epithelial cells lining the surface of the respiratory tract, inducing prominent necrotizing bronchitis and bronchiolitis and variable interstitial pneumonia. cell death is due to direct virus infection and to insult directed by leuk ...201424363301
protective efficacy in mice of monovalent and trivalent live attenuated influenza vaccines in the background of cold-adapted a/x-31 and b/lee/40 donor strains.influenza virus continues to take a heavy toll on human health and vaccination remains the mainstay of efforts to reduce the clinical impact imposed by viral infections. proven successful for establishing live attenuated vaccine donor strains, cold-adapted live attenuated influenza vaccines (caivs) have become an attractive modality for controlling the virus infection. previously, we developed the cold-adapted strains a/x-31 and b/lee/40 as novel donor strains of caivs against influenza a and b ...201424342248
egg- or cell culture-derived hemagglutinin mutations impair virus stability and antigen content of inactivated influenza vaccines.egg-derived viruses are the only available seed material for influenza vaccine production. vaccine manufacturing is done in embryonated chicken eggs, mdck or vero cells. in order to contribute to efficient production of influenza vaccines, we investigate whether the quality of inactivated vaccines is influenced by the propagation substrate. we demonstrate that h3n2 egg-derived seed viruses (a/brisbane/10/07, ivr147, and a/uruguay/716/07) triggered the hemagglutinin (ha) conformational change und ...201424323790
a single amino acid substitution in the hemagglutinin of h3n2 subtype influenza a viruses is associated with resistance to the long pentraxin ptx3 and enhanced virulence in mice.the long pentraxin, pentraxin 3 (ptx3), can play beneficial or detrimental roles during infection and disease by modulating various aspects of the immune system. there is growing evidence to suggest that ptx3 can mediate antiviral activity in vitro and in vivo. previous studies demonstrated that ptx3 and the short pentraxin serum amyloid p express sialic acids that are recognized by the hemagglutinin (ha) glycoprotein of certain influenza a viruses (iav), resulting in virus neutralization and an ...201424307735
drug susceptibility surveillance of influenza viruses circulating in the united states in 2011-2012: application of the who antiviral working group criteria.assessing susceptibility of influenza viruses to neuraminidase (na) inhibitors (nais) is primarily done in na inhibition (ni) assays, supplemented by na sequence analysis. however, two factors present challenges for ni assay data interpretation: lack of established ic50 values indicative of clinically relevant resistance and insufficient harmonization of ni testing methodologies among surveillance laboratories. in 2012, the who working group on influenza antiviral susceptibility (who-avwg) devel ...201424299049
antiviral susceptibility of variant influenza a(h3n2)v viruses isolated in the united states from 2011 to 2013.since 2011, outbreaks caused by influenza a(h3n2) variant [a(h3n2)v] viruses have become a public health concern in the united states. the a(h3n2)v viruses share the a(h1n1)pdm09 m gene containing the marker of m2 blocker resistance, s31n, but do not contain any known molecular markers associated with resistance to neuraminidase (na) inhibitors (nais). using a fluorescent na inhibition (ni) assay, the susceptibilities of recovered a(h3n2)v viruses (n=168) to fda-approved (oseltamivir and zanamiv ...201424449767
serum 25-hydroxyvitamin d level and influenza vaccine immunogenicity in children and adolescents.vaccination is an important strategy in the prevention of influenza, but immunologic response to vaccination can vary widely. recent studies have shown an association between serum 25-hydroxyvitamin d (25[oh]d) levels and immune function. the purpose of this study was to determine if serum 25(oh)d level correlates with influenza vaccine immunogenicity in children and adolescents.201424427274
synthesis, structure and inhibitory activity of a stereoisomer of oseltamivir carboxylate.a stereodivergent plan is presented leading to all eight stereoisomers of oseltamivir carboxylate (oc). key chemical manoeuvers are (1) a three-component vinylogous mukaiyama-mannich reaction, which sets the whole carbon skeleton and heteroatom substituents, and (2) an intramolecular, silylative mukaiyama aldol reaction, which creates the targeted carbocycle. the viability of the plan was demonstrated by the first total synthesis of 4-epi-oseltamivir carboxylate (6), accessed in 15 steps from gl ...201424425043
evaluation of heterosubtypic cross-protection against highly pathogenic h5n1 by active infection with human seasonal influenza a virus or trivalent inactivated vaccine immunization in ferret models.the threat of highly pathogenic avian influenza (hpai) h5n1 viruses to cause the next pandemic remains a major concern. here, we evaluated the cross-protection induced by natural infection of human seasonal influenza strains or immunization with trivalent inactivated influenza vaccine (tiv) against hpai h5n1 (a/vietnam/1203/2004) virus in ferrets. groups were treated with pbs (group a), infected with h1n1 (group b) or h3n2 (group c) virus, or immunized with tiv (group d). twelve weeks after the ...201424421115
establishment of serological herd profiles for zoonoses and production diseases in pigs by "meat juice multi-serology".the most important pork-borne zoonotic diseases in humans such as salmonelloses and yersinioses cause only latent infections in pigs. thus, the infection of pigs does not result in apparent or palpable alterations in the pig carcasses. this is the major reason, why the traditional meat inspection with adspection, palpation and incision is not able to control the food safety risks of today. the objective of this paper is to evaluate a set of serological tests, which provides a classification of p ...201424411983
immunogenicity of a 2009 pandemic influenza virus a h1n1 vaccine, administered simultaneously with the seasonal influenza vaccine, in children receiving chemotherapy.no examination of simultaneous vaccination against pandemic h1n1 and the seasonal influenza virus strains, in children with cancer receiving chemotherapy, are yet published. we investigated the immunogenicity of a whole-virion, inactivated, adjuvanted pandemic h1n1, and seasonal influenza vaccines administered simultaneously to children with cancer undergoing chemotherapy.201424395342
a historical perspective of influenza a(h1n2) virus.the emergence and transition to pandemic status of the influenza a(h1n1)a(h1n1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. within a short time of the initial emergence of a(h1n1)pdm09 virus, novel reassortants were isolated from swine. in late 2011, a variant (v) h3n2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase wit ...201424377419
viral aetiology influenza like illnesses in santa cruz, bolivia (2010-2012).acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of influenza like illnesses (ilis) remain largely unknown in developing countries. this study represents the first attempt to characterise viral aetiologies of ilis in bolivia.201424564892
intranasal vaccination with a replication-deficient influenza virus induces heterosubtypic neutralising mucosal iga antibodies in humans.we investigated the cross-neutralising potential of serum and nasal wash samples from volunteers who were intranasally immunised once with a monovalent replication-deficient delns1-h1n1 influenza virus vaccine (7.7log10tcid50/volunteer). eight out of twelve (8/12) vaccinees responded to vaccination with a significant increase of antibody levels in serum igg elisa, mucosal iga elisa, mna or hai. four responders showed delns1-specific elisa iga increases and revealed excellent homosubtypic neutral ...201424560674
in vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against influenza virus isolates in the 2011-2012 season in japan.the neuraminidase inhibitors oseltamivir phosphate (tamiflu®), zanamivir (relenza®), laninamivir octanoate (inavir®), and peramivir (rapiacta®) have been available for the treatment of influenza in japan since 2010. to assess the extent of viral resistance, we measured the 50% inhibitory concentration (ic₅₀) of each drug for influenza virus isolates from the 2011-2012 influenza season. specimens were obtained from patients prior to treatment. viral isolation was done using madine-darby canine ki ...201424560563
h3n2 virus as causative agent of ards requiring extracorporeal membrane oxygenation support.pandemic influenza virus a(h1n1) 2009 was associated with a higher risk of viral pneumonia in comparison with seasonal influenza viruses. the influenza season 2011-2012 was characterized by the prevalent circulation of influenza a(h3n2) viruses. whereas most h3n2 patients experienced mild, self-limited influenza-like illness, some patients were at increased risk for influenza complications because of age or underlying medical conditions. cases presented were patients admitted to the intensive ca ...201424527039
phylogenetic analysis of a swine influenza a(h3n2) virus isolated in korea in 2012.influenza a virus (iav) can infect avian and mammalian species, including humans. the genome nature of iavs may contribute to viral adaptation in different animal hosts, resulting in gene reassortment and the reproduction of variants with optimal fitness. as seen again in the 2009 swine-origin influenza a h1n1 pandemic, pigs are known to be susceptible to swine, avian, and human iavs and can serve as a 'mixing vessel' for the generation of novel iav variants. to this end, the emergence of swine ...201424523938
tmprss2 is a host factor that is essential for pneumotropism and pathogenicity of h7n9 influenza a virus in mice.cleavage of the hemagglutinin (ha) by host proteases is essential for the infectivity of influenza viruses. here, we analyzed the role of the serine protease tmprss2, which activates ha in the human respiratory tract, in pathogenesis in a mouse model. replication of the human h7n9 isolate a/anhui/1/13 and of human h1n1 and h3n2 viruses was compared in tmprss2 knockout (tmprss2(-/-)) and wild-type (wt) mice. knockout of tmprss2 expression inhibited h7n9 influenza virus replication in explants of ...201424522916
prospective surveillance and molecular characterization of seasonal influenza in a university cohort in singapore.southeast asia is believed to be a potential locus for the emergence of novel influenza strains, and therefore accurate sentinel surveillance in the region is critical. limited information exists on sentinel surveillance of influenza-like illness (ili) in young adults in singapore in a university campus setting. the objective of the present study was to determine the proportion of ili caused by influenza a and b viruses in a university cohort in singapore.201424520371
influenza a virus infections in marine mammals and terrestrial carnivores.influenza a viruses (iav), members of the orthomyxoviridae, cover a wide host spectrum comprising a plethora of avian and, in comparison, a few mammalian species. the viral reservoir and gene pool are kept in metapopulations of aquatic wild birds. the mammalian-adapted iavs originally arose by transspecies transmission from avian sources. in swine, horse and man, species-adapted iav lineages circulate independently of the avian reservoir and cause predominantly respiratory disease of highly vari ...201424511825
integrating influenza antigenic dynamics with molecular evolution.influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (hi) assay. here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phy ...201424497547
differences in antibody responses between trivalent inactivated influenza vaccine and live attenuated influenza vaccine correlate with the kinetics and magnitude of interferon signaling in children.live attenuated influenza vaccine (laiv) and trivalent inactivated influenza vaccine (tiv) are effective for prevention of influenza virus infection in children, but the mechanisms associated with protection are not well defined.201424495909
a new class of synthetic anti-lipopolysaccharide peptides inhibits influenza a virus replication by blocking cellular attachment.influenza a viruses are a continuous threat to human health as illustrated by the 2009 h1n1 pandemic. since circulating influenza virus strains become increasingly resistant against currently available drugs, the development of novel antivirals is urgently needed. here, we have evaluated a recently described new class of broad-spectrum antiviral peptides (synthetic anti-lipopolysaccharide peptides; salps) for their potential to inhibit influenza virus replication in vitro and in vivo. we found t ...201424486207
genetic characterization of influenza a viruses circulating in pigs and isolated in north-east spain during the period 2006-2007.swine influenza virus is one of the most important pathogens involved in the swine respiratory disease complex. recent serological surveys showed a high prevalence of swine influenza strains belonging to the h1n1, h1n2 and h3n2 subtypes circulating in pigs in spain. however, little is known about their genome sequence. five swine influenza strains were isolated from some unrelated outbreaks occurred during 2006-2007, and their complete genome sequences were determined. phylogenetic analysis reve ...201424461956
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
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
selection of dna aptamers that bind to influenza a viruses with high affinity and broad subtype specificity.many cases of influenza are reported worldwide every year. the influenza virus often acquires new antigenicity, which is known as antigenic shift; this results in the emergence of new virus strains, for which preexisting immunity is not found in the population resulting in influenza pandemics. in the event a new strain emerges, diagnostic tools must be developed rapidly to detect the novel influenza strain. the generation of high affinity antibodies is costly and takes time; therefore, an altern ...201424269231
human cytotoxic t lymphocytes directed to seasonal influenza a viruses cross-react with the newly emerging h7n9 virus.in february 2013, zoonotic transmission of a novel influenza a virus of the h7n9 subtype was reported in china. although at present no sustained human-to-human transmission has been reported, a pandemic outbreak of this h7n9 virus is feared. since neutralizing antibodies to the hemagglutinin (ha) globular head domain of the virus are virtually absent in the human population, there is interest in identifying other correlates of protection, such as cross-reactive cd8(+) t cells (cytotoxic t lympho ...201424257602
immunogenicity and safety of an inactivated 2012/2013 trivalent influenza vaccine produced in mammalian cell culture (optaflu®): an open label, uncontrolled study.the present study aimed to evaluate immunogenicity and safety of the 2012/2013 seasonal influenza vaccine (optaflu(®)) after the world health organization recommended two new strains for the composition.201424240428
a serological survey of canine h3n2, pandemic h1n1/09 and human seasonal h3n2 influenza viruses in dogs in china.influenza viruses have been isolated from dogs in china; however, the extent of influenza infection among dogs is not yet clear. here, we examined the seroprevalence of avian-origin canine h3n2, pandemic h1n1/09 and human seasonal h3n2 influenza viruses in pet dogs in china during january 2012 to june 2013. the seropositivity rate of canine h3n2, h1n1/09 and human h3n2 were 3.5%, 1.5%, and 1.2%, respectively. dogs aged 2-5 years were most commonly seropositive to canine h3n2 virus. it is worth n ...201424239170
genomic analysis of influenza a virus from captive wild boars in brazil reveals a human-like h1n2 influenza virus.influenza is a viral disease that affects human and several animal species. in brazil, h1n1, h3n2 and 2009 pandemic h1n1 a(h1n1)pdm09 influenza a viruses (iav) circulate in domestic swine herds. wild boars are also susceptible to iav infection but in brazil until this moment there are no reports of iav infection in wild boars or in captive wild boars populations. herein the occurrence of iav in captive wild boars with the presence of lung consolidation lesions during slaughter was investigated. ...201424238665
receptor binding and ph stability - how influenza a virus hemagglutinin affects host-specific virus infection.influenza a virus strains adopt different host specificities mainly depending on their hemagglutinin (ha) protein. via ha, the virus binds sialic acid receptors of the host cell and, upon endocytic uptake, ha triggers fusion between the viral envelope bilayer and the endosomal membrane by a low ph-induced conformational change leading to the release of the viral genome into the host cell cytoplasm. both functions are crucial for viral infection enabling the genesis of new progeny virus. adaptati ...201424161712
plc-γ1 signaling plays a subtype-specific role in postbinding cell entry of influenza a virus.host signaling pathways and cellular proteins play important roles in the influenza viral life cycle and can serve as antiviral targets. in this study, we report the engagement of host phosphoinositide-specific phospholipase γ1 (plc-γ1) in mediating cell entry of influenza virus h1n1 but not h3n2 subtype. both plc-γ1-specific inhibitor and short hairpin rna (shrna) strongly suppress the replication of h1n1 but not h3n2 viruses in cell culture, suggesting that plc-γ1 plays an important subtype-sp ...201424155396
activation of influenza a viruses by host proteases from swine airway epithelium.pigs are important natural hosts of influenza a viruses, and due to their susceptibility to swine, avian, and human viruses, they may serve as intermediate hosts supporting adaptation and genetic reassortment. cleavage of the influenza virus surface glycoprotein hemagglutinin (ha) by host cell proteases is essential for viral infectivity. most influenza viruses, including human and swine viruses, are activated at a monobasic ha cleavage site, and we previously identified tmprss2 and hat to be re ...201424155384
newly emerging mutations in the matrix genes of the human influenza a(h1n1)pdm09 and a(h3n2) viruses reduce the detection sensitivity of real-time reverse transcription-pcr.new variants of the influenza a(h1n1)pdm09 and a(h3n2) viruses were detected in taiwan between 2012 and 2013. some of these variants were not detected in clinical specimens using a common real-time reverse transcription-pcr (rt-pcr) assay that targeted the conserved regions of the viral matrix (m) genes. an analysis of the m gene sequences of the new variants revealed that several newly emerging mutations were located in the regions where the primers or probes of the real-time rt-pcr assay bind; ...201424153120
molecular epidemiology of influenza a virus infection in cyprus in four consecutive seasons (2009 pandemic-2013).the aim of this study was to investigate the epidemiology of influenza a virus infection in cyprus from the 2009 pandemic until 2013. pandemic influenza a(h1n1)2009 virus infections outnumbered infections with other respiratory viruses until the end of 2009. the pandemic virus was also the prevalent influenza strain during influenza season 2010-2011; however, it was completely replaced by h3n2 subtype in the next season. during the most recent influenza season, 2012-2013, the pandemic strain was ...201424152574
administration of as03b-adjuvanted a(h1n1)pdm09 vaccine in children aged <3 years enhances antibody response to h3 and b viruses following a single dose of trivalent vaccine one year later.we report on a follow-up clinical and serological investigation of 274 children who received seasonal influenza vaccine (trivalent inactivated vaccine [tiv]) 1 year after receipt of either as03(b)-adjuvanted subunit or whole virus monovalent a(h1n1)pdm09 vaccine and describe the antibody responses to the h3n2 a/perth/16/2009 and b/brisbane/60/2008 components of tiv.201424149079
review of 10 years of clinical experience with chinese domestic trivalent influenza vaccine anflu®.influenza viruses cause annual winter epidemics globally and influenza vaccination is most effective way to prevent the disease or severe outcomes from the illness, especially in developing countries. however, the majority of the world's total production capacity of influenza vaccine is concentrated in several large multinational manufacturers. a safe and effective preventive vaccine for the developing countries is urgent. anflu®, a chinese domestic preservative-free, split-virus trivalent influ ...201424104060
surveillance of human influenza a(h3n2) virus from 1999 to 2009 in southern italy.the aim of this study was to evaluate the presence of influenza virus co-infections in humans and changes in the genetic variability of a(h3n2) virus strains in southern italy from 1999 to 2009. a partial sequence of the haemagglutinin (ha) gene by human influenza h3n2 strains identified in oropharyngeal swabs from patients with influenza-like illness was analysed by dna sequencing and a phylogenetic analysis was performed. during the seasons 1999-2000, 2002-2003, 2004-2005 and 2008-2009, the in ...201423967903
incorporation of a proteotyping approach using mass spectrometry for surveillance of influenza virus in cell-cultured strains.the reemergence of deadly pandemic influenza virus strains has necessitated the development of improved methods for rapid detection and subtyping of influenza viruses that will enable more strains to be characterized at the molecular level. representative circulating strains of human influenza viruses from primary clinical specimens were grown in cell culture, purified through polyethylene glycol precipitation, proteolytically digested with an endoproteinase, and analyzed and identified by high- ...201424226917
influenza vaccine effectiveness in the 2011-2012 season: protection against each circulating virus and the effect of prior vaccination on estimates.each year, the us influenza vaccine effectiveness network examines the effectiveness of influenza vaccines in preventing medically attended acute respiratory illnesses caused by influenza.201424235265
prevalence of antibodies to european porcine influenza viruses in humans living in high pig density areas of germany.the risk of zoonotic human infection caused by european porcine influenza virus strains was estimated in german regions with a high pig density. sera from 622 healthy volunteers were collected between april 2009 and november 2011, mainly in westphalia and western lower saxony. these included 362 subjects with occupational contact to pigs and 260 blood donors without any direct exposition to pigs. samples were analysed by the haemagglutination inhibition (hi) assay against a panel of six swine vi ...201424013183
survival of influenza virus on human fingers.indirect transmission of the influenza virus via finger contamination with respiratory mucus droplets has been hypothesized to contribute to transmission in the community. under laboratory conditions, influenza-infected respiratory droplets were reconstituted as close as possible to natural conditions. we investigated experimentally the survival of influenza a (h3n2) and a (h1n1)pdm09 viruses on human fingers. infectious virus was easily recoverable on all fingers 1 min after fingertip contamina ...201423927722
mortality attributable to seasonal and pandemic influenza, australia, 2003 to 2009, using a novel time series smoothing approach.official statistics under-estimate influenza deaths. time series methods allow the estimation of influenza-attributable mortality. the methods often model background, non-influenza mortality using a cyclic, harmonic regression model based on the serfling approach. this approach assumes that the seasonal pattern of non-influenza mortality is the same each year, which may not always be accurate.201423755139
antivirally active ribavirin analogues--4,5-disubstituted 1,2,3-triazole nucleosides: biological evaluation against certain respiratory viruses and computational modelling.ribavirin is a broad-spectrum antiviral agent that derives some of its activity from inhibition of cellular inosine monophosphate dehydrogenase (impdh), resulting in lower guanosine triphosphate (gtp) levels. here we report the biological activities of three ribavirin analogues.201423538746
first report of seroprevalence of swine influenza a virus in tibetan pigs in tibet, china.swine influenza a virus (siv) is zoonotic pathogen that can be acquired by food-borne transmission because food animals, for example pigs, are recognized as a reservoir. the objectives of this study were to determine the seroprevalence of anti-siv (h1n1 and h3n2) in tibetan pigs in tibet nationality autonomous region, china, a region with cold weather and high altitude. a total of 421 serum samples were randomly collected from tibetan pigs in tibet and were evaluated for antibodies against siv u ...201423955014
detection of influenza a virus nucleoprotein antibodies in oral fluid specimens from pigs infected under experimental conditions using a blocking elisa.in commercial swine populations, influenza is an important component of the porcine respiratory disease complex (prdc) and a pathogen with major economic impact. previously, a commercial blocking elisa (flockchek(™) avian influenza virus multis-screen(®) antibody test kit, idexx laboratories, inc., westbrook, me, usa) designed to detect influenza a nucleoprotein (np) antibodies in avian serum was shown to accurately detect np antibodies in swine serum. the purpose of this study was to determine ...201423046061
european surveillance network for influenza in pigs: surveillance programs, diagnostic tools and swine influenza virus subtypes identified in 14 european countries from 2010 to 2013.swine influenza causes concern for global veterinary and public health officials. in continuing two previous networks that initiated the surveillance of swine influenza viruses (sivs) circulating in european pigs between 2001 and 2008, a third european surveillance network for influenza in pigs (esnip3, 2010-2013) aimed to expand widely the knowledge of the epidemiology of european sivs. esnip3 stimulated programs of harmonized siv surveillance in european countries and supported the coordinatio ...201425542013
characteristics of influenza ha-na interdependence determined through a graphical technique.influenza viruses are characterized by two surface proteins - the hemagglutinin (ha) of which there are 16 varieties, and the neuraminidase (na) of which there are 9, each subtype characterized by its antigenic properties. although theoretically 16 x 9 combinations are possible, only a few like the h1n1, h3n2, etc are seen to occur more frequently. numerous studies with select subtypes like h1n1, h5n1, etc., have explained this phenomena by indicating that viral viability necessitates functional ...201425794303
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
[mutations in the neuraminidase gene of the epidemic influenza virus strain isolated in the 2012-2013 season and improvement of a pcr assay for the detection of influenza virus].in 2011, we developed a real-time rt-pcr method to rapidly and sensitively detect three subtypes of influenza a virus [h1n1, h3n2, and influenza (h1n1) 2009] and influenza b virus (the conventional pcr method). this method was useful during the 2011-2012 epidemic season. however, epidemic influenza a virus strain h3n2 in the 2012-2013 season was undetectable by this method, possibly due to mutation in the neuraminidase (na) gene of epidemic influenza a virus strain h3n2. therefore, we improved t ...201427526538
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
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
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
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
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
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
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
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
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
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
characterization of human influenza viruses in lebanon during 2010-2011 and 2011-2012 post-pandemic seasons.to genetically characterize human influenza viruses and their susceptibilities to antivirals during two post-pandemic seasons in lebanon.201425301400
serial intervals of respiratory infectious diseases: a systematic review and analysis.the serial interval of an infectious disease represents the duration between symptom onset of a primary case and symptom onset of its secondary cases. a good evidence base for such values is essential, because they allow investigators to identify epidemiologic links between cases and serve as an important parameter in epidemic transmission models used to design infection control strategies. we reviewed the literature for available data sets containing serial intervals and for reported values of ...201425294601
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
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
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