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combinations of 1,8-cineol and oseltamivir for the treatment of influenza virus a (h3n2) infection in mice.it is need for development of new means against influenza virus due to the lack of efficacy of available therapeutic strategies. in previous research, 1,8-cineol exert its inhibition of nuclear factor (nf)-κb, the main regulator of cytokine and chemokine production in influenza, and anti-inflammatory activity. these fact supports and helps establish the hypothesis that 1,8-cineol may have synergism with an antiviral on influenza virus infection. the combined effect of 1,8-cineol with oseltamivir ...201627966790
alternative progenitor lineages regenerate the adult lung depleted of alveolar epithelial type 2 cells.an aberrant oxygen environment at birth increases the severity of respiratory viral infections later in life through poorly understood mechanisms. here, we show that alveolar epithelial cell (aec) 2 cells (aec2s), progenitors for aec1 cells, are depleted in adult mice exposed to neonatal hypoxia or hyperoxia. airway cells expressing surfactant protein (sp)-c and atp binding cassette subfamily a member 3, alveolar pod cells expressing keratin (krt) 5, and pulmonary fibrosis were observed when the ...201727967234
whole-genome characterization of a novel human influenza a(h1n2) virus variant, brazil.we report the characterization of a novel reassortant influenza a(h1n2) virus not previously reported in humans. recovered from a a pig farm worker in southeast brazil who had influenza-like illness, this virus is a triple reassortant containing gene segments from subtypes h1n2 (hemagglutinin), h3n2 (neuraminidase), and pandemic h1n1 (remaining genes).201727983507
national influenza surveillance in the philippines from 2006 to 2012: seasonality and circulating strains.the results of routine influenza surveillance in 13 regions in the philippines from 2006 to 2012 are presented, describing the annual seasonal epidemics of confirmed influenza virus infection, seasonal and alert thresholds, epidemic curve, and circulating influenza strains.201627993136
simultaneous detection of influenza a subtypes of h3n2 virus, pandemic (h1n1) 2009 virus and reassortant avian h7n9 virus in humans by multiplex one-step real-time rt-pcr assay.influenza a virus is a leading causative pathogen of human acute respiratory infection. recently, the co-circulation of pandemic (h1n1) 2009 and seasonal h3n2 viruses was reported, and sporadic cases with reassortant avian h7n9 virus are continually reported in china. we aimed to establish a multiplex one-step real-time reverse transcription-polymerase chain reaction (rrt-pcr) assay to simultaneously detect and discriminate flua subtypes, including human seasonal h3n2 virus, pandemic (h1n1) 2009 ...201627995031
evaluation of a candidate live attenuated influenza vaccine prepared in changchun bcht (china) for safety and efficacy in ferrets.we evaluated the safety and efficacy of a live attenuated influenza vaccine (laiv) product in ferrets. the bcht laiv product was significantly less virulent than wild-type h1n1 virus, when evaluated by comparing virus shedding and histopathologic lesions. the data indicated strong evidence for an attenuated phenotype of laiv. furthermore, the vaccine induced robust humoral immune responses in seronegative ferrets, and protected ferrets against development of fever, weight loss and turbinate infl ...201627997342
structural basis of influenza virus fusion inhibition by the antiviral drug arbidol.the broad-spectrum antiviral drug arbidol shows efficacy against influenza viruses by targeting the hemagglutinin (ha) fusion machinery. however, the structural basis of the mechanism underlying fusion inhibition by arbidol has remained obscure, thereby hindering its further development as a specific and optimized influenza therapeutic. we determined crystal structures of arbidol in complex with influenza virus ha from pandemic 1968 h3n2 and recent 2013 h7n9 viruses. arbidol binds in a hydrophob ...201728003465
ns1 protein amino acid changes d189n and v194i affect interferon responses, thermosensitivity, and virulence of circulating h3n2 human influenza a viruses.influenza virus ns1 protein is a nonstructural, multifunctional protein that counteracts host innate immune responses, modulating virus pathogenesis. ns1 protein variability in subjects infected with h3n2 influenza a viruses (iavs) during the 2010/2011 season was analyzed, and amino acid changes in residues 86, 189, and 194 were found. the consequences of these mutations for the ns1-mediated inhibition of ifn responses and the pathogenesis of the virus were evaluated, showing that ns1 mutations ...201728003482
detection of d151g/n mutations in the neuraminidase gene of influenza a (h3n2) viruses by real-time rt-pcr allelic discrimination assay.single nucleotide polymorphisms (snps) at d151 position of neuraminidase (na) gene of influenza a (h3n2) virus has been associated with drug resistance and increased binding affinity. na-d151g/n-substitutions of influenza a (h3n2) viruses are frequently induced and selected by culturing in madin-darby canine kidney (mdck) cell lines. it is important to consider and exclude d151g/n mutants after isolation of influenza virus in mdck cell line; since, the substitutions can highly influence the resu ...201628004398
impact of influenza in the post-pandemic phase: clinical features in hospitalized patients with influenza a (h1n1) pdm09 and h3n2 viruses, during 2013 in santa fe, argentina.it is important to characterize the clinical and epidemiological pattern of the influenza a (h1n1) pdm09 virus and compare it with influenza a (h3n2) virus, as surveyed in just a few studies, in order to contribute to the implementation and strengthening of influenza control and prevention strategies. the aims in this study were to describe influenza clinical and epidemiological characteristics in hospitalized patients, caused by influenza a (h1n1)pdm09 and influenza a (h3n2) viruses during 2013 ...201628004402
an intranasal proteosome-adjuvanted trivalent influenza vaccine is safe, immunogenic & efficacious in the human viral influenza challenge model. serum igg & mucosal iga are important correlates of protection against illness associated with infection.a proteosome-adjuvanted trivalent inactivated influenza vaccine (p-tiv) administered intra-nasally was shown to be safe, well tolerated and immunogenic in both systemic and mucosal compartments, and effective at preventing illness associated with evidence of influenza infection.201628005959
human seasonal influenza a viruses induce h7n9-cross-reactive antibody-dependent cellular cytotoxicity (adcc) antibodies that are directed towards the nucleoprotein.antibodies that mediate antibody-dependent cellular cytotoxicity (adcc) against avian influenza virus subtypes including h7n9 and h5n1 have been detected in human sera. there are limited data on the presence of such cross-reactive adcc mediating antibodies (adcc-abs) in children and the viral target(s) of these abs are poorly understood. using high-throughput nk cell activation and nk cytotoxicity assays, we compared adcc-abs in sera collected from healthy infants (≤1 year), children (2-17 years ...201628011910
recent h3n2 viruses have evolved specificity for extended, branched human-type receptors, conferring potential for increased avidity.human and avian influenza viruses recognize different sialic acid-containing receptors, referred to as human-type (neuacα2-6gal) and avian-type (neuacα2-3gal), respectively. this presents a species barrier for aerosol droplet transmission of avian viruses in humans and ferrets. recent reports have suggested that current human h3n2 viruses no longer have strict specificity toward human-type receptors. using an influenza receptor glycan microarray with extended airway glycans, we find that h3n2 vi ...201728017661
connective tissue growth factor promotes pulmonary epithelial cell senescence and is associated with copd severity.the purpose of this study was to determine whether expression of connective tissue growth factor (ctgf) protein in chronic obstructive pulmonary disease (copd) is consistent in humans and animal models of copd and to investigate the role of this protein in lung epithelial cells. ctgf in lung epithelial cells of ex-smokers with copd was compared with ex-smokers without copd by immunofluorescence. a total of twenty c57bl/6 mice and sixteen non-human primates (nhps) were exposed to cigarette smoke ...201728026993
frequency of influenza h3n2 intra-subtype reassortment: attributes and implications of reassortant spread.increasing evidence suggests that influenza reassortment not only contributes to the emergence of new human pandemics but also plays an important role in seasonal influenza epidemics, disease severity, evolution, and vaccine efficacy. we studied this process within 2091 h3n2 full genomes utilizing a combination of the latest reassortment detection tools and more conventional phylogenetic analyses.201628034300
coherence of influenza surveillance data across different sources and age groups, beijing, china, 2008-2015.influenza is active during the winter and spring in the city of beijing, which has a typical temperate climate with four clear distinct seasons. the clinical and laboratory surveillance data for influenza have been used to construct critical indicators for influenza activities in the community, and previous studies have reported varying degrees of association between laboratory-confirmed influenza specimens and outpatient consultation rates of influenza-like illness in subtropical cities. howeve ...201628036373
intranasal immunization using mannatide as a novel adjuvant for an inactivated influenza vaccine and its adjuvant effect compared with mf59.intranasal vaccination is more potent than parenteral injection for the prevention of influenza. however, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. the immunomodulator mannatide or polyactin (pa) has been used for the clinical treatment of impaired immunity in china, but its adjuvant effect on an inactivated trivalent influenza vaccine (itiv) via intranasal vaccination is unclear. to ex ...201728052136
optimization of a quantitative micro-neutralization assay.the micro-neutralization (mn) assay is a standard technique for measuring the infectivity of the influenza virus and the inhibition of virus replication. in this study, we present the protocol of an imaging-based mn assay to quantify the true antigenic relationships between viruses. unlike typical plaque reduction assays that rely on visible plaques, this assay quantitates the entire infected cell population of each well. the protocol matches the virus type or subtype with the selection of cell ...201628060291
chimeric virus-like particles containing influenza ha antigen and gpi-ccl28 induce long-lasting mucosal immunity against h3n2 viruses.influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. the duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. in the current study, we examined the long-lasting protective efficacy of chimeric vlps (cvlps) containing influenza ha and gpi-anchored ccl28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. we report that the cvlps induced signi ...201728067290
influenza vaccine effectiveness in the netherlands from 2003/2004 through 2013/2014: the importance of circulating influenza virus types and subtypes.influenza vaccine effectiveness (ive) varies over different influenza seasons and virus (sub)types/lineages. to assess the association between ive and circulating influenza virus (sub)types/lineages, we estimated the overall and (sub)type specific ive in the netherlands. we conducted a test-negative case control study among subjects with influenza-like illness or acute respiratory tract infection consulting the sentinel practices over 11 influenza seasons (2003/2004 through 2013/2014) in the net ...201728068386
detection of antigenic variants of subtype h3 swine influenza a viruses from clinical samples.a large population of genetically and antigenically diverse influenza a viruses (iavs) are circulating among the swine population, playing an important role in influenza ecology. swine iavs not only cause outbreaks among swine but also can be transmitted to humans, causing sporadic infections and even pandemic outbreaks. antigenic characterizations of swine iavs are key to understanding the natural history of these viruses in swine and to selecting strains for effective vaccines. however, influe ...201728077698
[differential diagnosis of the viral etiology of suspected mumps in a population with high vaccine coverage].in this study, buccal swabs from patients with the clinical picture of parotitis epidemica in whom mumps virus (mv) infection was not confirmed by direct detection or serologically were tested. the aim was to detect by molecular methods nucleic acids (nas) of other respiratory viruses possibly involved in salivary gland swelling. at the same time, paired sera, if available, were tested.201628078898
radix isatidis polysaccharides inhibit influenza a virus and influenza a virus-induced inflammation via suppression of host tlr3 signaling in vitro.influenza remains one of the major epidemic diseases worldwide, and rapid virus replication and collateral lung tissue damage caused by excessive pro-inflammatory host immune cell responses lead to high mortality rates. thus, novel therapeutic agents that control influenza a virus (iav) propagation and attenuate excessive pro-inflammatory responses are needed. polysaccharide extract from radix isatidis, a traditional chinese herbal medicine, exerted potent anti-iav activity against human seasona ...201728085062
a virus-like particle vaccination strategy expands its tolerance to h3n2 antigenic drift by enhancing neutralizing antibodies against hemagglutinin stalk.seasonal influenza viruses impact public health annually due to their continual evolution. however, the current inactivated seasonal vaccines provide poor protection against antigenically drifted viruses and require periodical reformulation through hit-and-miss predictions about which strains will circulate during the next season. to reduce the impact caused by vaccine mismatch, we investigated the drift-tolerance of virus-like particles (vlp) as an improved vaccine candidate. the cross-protecti ...201728093338
pathogenicity of modified bat influenza virus with different m genes and its reassortment potential with swine influenza a virus.in our previous studies the reassortant virus containing only the pr8 h1n1 matrix (m) gene in the background of the modified bat influenza bat09:mh1mn1 virus could be generated. however, whether m genes from other origins can be rescued in the background of the bat09:mh1mn1 virus and whether the resulting novel reassortant virus is virulent remain unknown. herein, two reassortant viruses were generated in the background of the bat09:mh1mn1 virus containing either a north american or a eurasian s ...201728100299
a multiplex rt-pcr assay for detection and differentiation of avian-origin canine h3n2, equine-origin h3n8, human-origin h3n2, and h1n1/2009 canine influenza viruses.virological and serological surveys have documented that h1n1/2009, avian-origin canine h3n2 (ch3n2), seasonal human-origin h3n2 (hh3n2), and equine-origin h3n8 influenza viruses are consistently circulating in dogs. in the present study, a multiplex reverse-transcriptase polymerase chain reaction (mrt-pcr) assay was developed for simultaneous detection and differentiation of these influenza viruses. four primer sets were designed to target the hemagglutinin genes of h1n1/2009, ch3n2, hh3n2, and ...201728107507
influenza a virus upregulates prpf8 gene expression to increase virus production.a ddrt-pcr analysis was performed to detect cellular genes that are differentially expressed after influenza a virus (h1n1) infection of a549 cells. after ddrt-pcr, eight dna fragments were identified. prpf8, one of the cellular genes that were upregulated after virus infection, was further analyzed since it has previously been identified as a cellular factor required for influenza virus replication. the upregulation of prpf8 gene expression after viral infection was confirmed using real-time rt ...201728110426
in vitro characterization of the novel h3n1 reassortant influenza viruses from quail.quail is considered as an intermediate host for generation of the novel reassortant influenza a viruses (iavs). in this study, we evaluated the replication ability of the three novel h3n1 reassortant viruses recovered from pandemic h1n1 2009 (ph1n1) and duck h3n2 (dkh3n2) co-infected quail generated from our previous study in embryonated chicken eggs, mammalian (mdck) and human lung derived (a549) cells. our study demonstrated that all of the reassortant viruses replicated efficiently in avian a ...201728110788
mechanistic perspective of the oxido-immunopathologic resolution property of kolaviron in mice influenza pneumonitis.implicated in influenza-associated pathology are innate defence overzealousness and unabated secretion of oxidative tissue-sensitive antimicrobial agents. at different time points, mice were pre-treated with kolaviron (400 mg/kg), a natural antioxidant and anti-inflammatory agent, and subsequently challenged with 2 ld50 influenza a/h3n2/perth/16/09 virus. after euthanasia at day 6, blood, lungs, liver and spleen were collected and processed for biochemical, immunohistochemical and flow cytometri ...201728116826
rules of co-occurring mutations characterize the antigenic evolution of human influenza a/h3n2, a/h1n1 and b viruses.the human influenza viruses undergo rapid evolution (especially in hemagglutinin (ha), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system. therefore, the vaccine has to be updated every year to stay effective. there is a need to characterize the evolution of influenza viruses for better selection of vaccine candidates and the prediction of pandemic strains. studies have shown that the influenza hemagglutinin evolution is dr ...201628117657
one-pot reverse transcriptional loop-mediated isothermal amplification (rt-lamp) for detecting mers-cov.due to the limitation of rapid development of specific antiviral drug or vaccine for novel emerging viruses, an accurate and rapid diagnosis is a key to manage the virus spread. we developed an efficient and rapid method with high specificity for the middle east respiratory syndrome coronavirus (mers-cov), based on one-pot reverse transcription loop-mediated isothermal amplification (one-pot rt-lamp). a set of six lamp primers [f3, b3, fip, bip, lf (loop-f), and lb (loop-b)] were designed using ...201628119682
improving the selection and development of influenza vaccine viruses - report of a who informal consultation on improving influenza vaccine virus selection, hong kong sar, china, 18-20 november 2015.since 2010 the who has held a series of informal consultations to explore ways of improving the currently highly complex and time-pressured influenza vaccine virus selection and development process. in november 2015 experts from around the world met to review the current status of efforts in this field. discussion topics included strengthening influenza surveillance activities to increase the availability of candidate vaccine viruses and improve the extent, timeliness and quality of surveillance ...201728131392
microrna-146a induction during influenza h3n2 virus infection targets and regulates traf6 levels in human nasal epithelial cells (hnecs).we have previously shown that human nasal epithelial cells (hnecs) are highly permissive cells for respiratory viruses including influenza a virus (iav) and respiratory syncytial virus. recent studies have indicated that micrornas (mirnas) are involved in virus-host relationship, and this led us to investigate its essential roles in the in vitro hnecs model derived from multiple donors. by comparing the differential expression of mirnas upon iav infection among animal and cell line studies, cand ...201728131813
antigenic and genetic characterization of influenza viruses circulating in bulgaria during the 2015/2016 season.influenza virological surveillance is an essential tool for early detection of novel genetic variants of epidemiologic and clinical significance. the aim of this study was to determine the antigenic and molecular characteristics of influenza viruses circulating in bulgaria during the 2015/2016 season. the season was characterized by dominant circulation of a(h1n1)pdm09 viruses, accounting for 66% of detected influenza viruses, followed by b/victoria-lineage viruses (24%) and a(h3n2) viruses (10% ...201728132927
vaccination has minimal impact on the intrahost diversity of h3n2 influenza viruses.while influenza virus diversity and antigenic drift have been well characterized on a global scale, the factors that influence the virus' rapid evolution within and between human hosts are less clear. given the modest effectiveness of seasonal vaccination, vaccine-induced antibody responses could serve as a potent selective pressure for novel influenza variants at the individual or community level. we used next generation sequencing of patient-derived viruses from a randomized, placebo-controlle ...201728141862
respiratory viruses in acute exacerbations of chronic obstructive pulmonary disease.acute exacerbations of chronic obstructive pulmonary disease (aecopd) cause significant morbidity, mortality, and an inexorable decline of lung function. data from developed countries have shown viruses to be important causes of aecopd, but data from developing countries like india are scant. we set out to determine the contribution of viruses in the causation of hospitalized patients with aecopd.201728144057
molecular modeling and lead design of substituted zanamivir derivatives as potent anti-influenza drugs.influenza virus spreads infection by two main surface glycoproteins, namely hemagglutinin (ha) and neuraminidase (na). na cleaves the sialic acid receptors eventually releasing newly formed virus particles which then invade new cells. inhibition of na could limit the replication of virus to one round which is insufficient to cause the disease.201628155702
consensus m2e peptide conjugated to gold nanoparticles confers protection against h1n1, h3n2 and h5n1 influenza a viruses.the extracellular domain of influenza a ion channel membrane matrix protein 2 (m2e) is considered to be a potential candidate to develop a universal influenza a vaccine. however poor immunogenicity of m2e presents a significant roadblock. we have developed a vaccine formulation comprising of the consensus m2e peptide conjugated to gold nanoparticles (aunps) with cpg as a soluble adjuvant (aunp-m2e + scpg). we demonstrate that intranasal delivery of aunp-m2e + scpg in mice induces lung b cell act ...201728161578
the characteristics and antigenic properties of recently emerged subclade 3c.3a and 3c.2a human influenza a(h3n2) viruses passaged in mdck cells.two new subclades of influenza a(h3n2) viruses became prominent during the 2014-2015 northern hemisphere influenza season. the ha glycoproteins of these viruses showed sequence changes previously associated with alterations in receptor-binding properties. to address how these changes influence virus propagation, viruses were isolated and propagated in conventional mdck cells and mdck-siat1 cells, cells with enhanced expression of the human receptor for the virus, and analysed at each passage.201728164446
a universal computational model for predicting antigenic variants of influenza a virus based on conserved antigenic structures.rapid determination of the antigenicity of influenza a virus could help identify the antigenic variants in time. currently, there is a lack of computational models for predicting antigenic variants of some common hemagglutinin (ha) subtypes of influenza a viruses. by means of sequence analysis, we demonstrate here that multiple ha subtypes of influenza a virus undergo similar mutation patterns of ha1 protein (the immunogenic part of ha). further analysis on the antigenic variation of influenza a ...201728165025
excess mortality associated with influenza after the 2009 h1n1 pandemic in a subtropical city in china, 2010-2015.the aim of this study was to use a quasi-poisson regression model to estimate the mortality burden associated with influenza type/subtypes in a subtropical city in china, for the years 2010-2015.201728167255
a live-attenuated influenza vaccine for h3n2 canine influenza virus.canine influenza is a contagious respiratory disease in dogs caused by two subtypes (h3n2 and h3n8) of canine influenza virus (civ). currently, only inactivated influenza vaccines (iivs) are available for the prevention of civs. historically, live-attenuated influenza vaccines (laivs) have been shown to produce better immunogenicity and protection efficacy than iivs. here, we have engineered a civ h3n2 laiv by using the internal genes of a previously described civ h3n8 laiv as a master donor vir ...201728167384
bayesian phylogeography of influenza a/h3n2 for the 2014-15 season in the united states using three frameworks of ancestral state reconstruction.ancestral state reconstructions in bayesian phylogeography of virus pandemics have been improved by utilizing a bayesian stochastic search variable selection (bssvs) framework. recently, this framework has been extended to model the transition rate matrix between discrete states as a generalized linear model (glm) of genetic, geographic, demographic, and environmental predictors of interest to the virus and incorporating bssvs to estimate the posterior inclusion probabilities of each predictor. ...201728170397
progesterone-based contraceptives reduce adaptive immune responses and protection against sequential influenza a virus infections.in addition to their intended use, progesterone (p4)-based contraceptives promote anti-inflammatory immune responses, yet their effects on the outcome of infectious diseases, including influenza a virus (iav) infection, are rarely evaluated. to evaluate their impact on immune responses to sequential iav infections, adult female mice were treated with placebo or one of two progestins, p4 or levonorgestrel (lng), and infected with a mouse-adapted h1n1 (mah1n1) virus. treatment with p4 or lng reduc ...201728179523
co-infection with influenza viruses and influenza-like virus during the 2015/2016 epidemic season.concerning viral infection of the respiratory system, a single virus can cause a variety of clinical symptoms and the same set of symptoms can be caused by different viruses. moreover, infection is often caused by a combination of viruses acting at the same time. the present study demonstrates, using multiplex rt-pcr and real-time qrt-pcr, that in the 2015/2016 influenza season, co-infections were confirmed in patients aged 1 month to 90 years. we found 73 co-infections involving influenza virus ...201728181195
circulation of antibodies against influenza virus hemagglutinins in the 2014/2015 epidemic season in poland.the aim of this study was to determine the level of anti-hemagglutinin antibodies in the serum of people in different age-groups during the 2014/2015 epidemic influenza season in poland. a total of 1050 sera were tested. the level of anti-hemagglutinin antibodies was determined using the hemagglutinin inhibition test. the results provided information on the incidence of circulating a/california/7/2009(h1n1)pdm09, a/texas/50/2012(h3n2), and b/massachusetts/2/2012 viruses. the level of antibodies ...201728181197
complete genome sequence of a novel influenza a h1n2 virus circulating in swine from central bajio region, mexico.the aim of this study was to perform the complete genome sequence of a swine influenza a h1n2 virus strain isolated from a pig in guanajuato, méxico (a/swine/mexico/gtodmzc01/2014) and to report its seroprevalence in 86 counties at the central bajio zone. to understand the evolutionary dynamics of the isolate, we undertook a phylogenetic analysis of the eight gene segments. these data revealed that the isolated virus is a reassortant h1n2 subtype, as its genes are derived from human (ha, np, pa) ...201728181421
effectiveness of seasonal influenza vaccination in community-dwelling elderly people: an individual participant data meta-analysis of test-negative design case-control studies.several aggregate data meta-analyses have provided estimates of the effectiveness of influenza vaccination in community-dwelling elderly people. however, these studies ignored the effects of patient-level confounders such as sex, age, and chronic diseases that could bias effectiveness estimates. we aimed to assess the confounder-adjusted effectiveness of influenza vaccines on laboratory-confirmed influenza among elderly people by conducting a global individual participant data meta-analysis.201728189522
defining the antibody cross-reactome directed against the influenza virus surface glycoproteins.infection with influenza virus induces antibodies to the viral surface glycoproteins hemagglutinin and neuraminidase, and these responses can be broadly protective. to assess the breadth and magnitude of antibody responses, we sequentially infected mice, guinea pigs and ferrets with divergent h1n1 or h3n2 subtypes of influenza virus. we measured antibody responses by elisa of an extensive panel of recombinant glycoproteins representing the viral diversity in nature. guinea pigs developed high ti ...201728192418
suppressor of cytokine signaling (socs)5 ameliorates influenza infection via inhibition of egfr signaling.influenza virus infections have a significant impact on global human health. individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as copd, are particularly susceptible to influenza. here we show that suppressor of cytokine signaling (socs) five has a pivotal role in restricting influenza a virus in the airway epithelium, through the regulation of epidermal growth factor receptor (egfr). socs5-deficient mice exhibit heightened disease severity, with increas ...201728195529
selection of multi-drug resistant influenza a and b viruses under zanamivir pressure and their replication fitness in ferrets.intravenous zanamivir has been used to treat patients with severe influenza. because the majority of cases (including immunocompromised patients) require the drug for an extended period of treatment, there is a higher risk that the virus will develop resistance. therefore, knowing the possible amino acid substitutions that may arise in recently circulating influenza strains under prolonged zanamivir exposure and their impact on antiviral susceptibility is important.201728195559
interim estimates of 2016/17 vaccine effectiveness against influenza a(h3n2), canada, january 2017.using a test-negative design, the canadian sentinel practitioner surveillance network (spsn) assessed interim 2016/17 influenza vaccine effectiveness (ve) against dominant influenza a(h3n2) viruses considered antigenically matched to the clade 3c.2a vaccine strain. sequence analysis revealed substantial heterogeneity in emerging 3c.2a1 variants by province and over time. adjusted ve was 42% (95% confidence interval: 18-59%) overall, with variation by province. interim virological and ve findings ...201728205503
prospective surveillance of antiviral resistance in hospitalized infants less than 12 months of age with a(h3n2) influenza infection and treated with oseltamivir.infants exhibit elevated influenza virus loads and prolonged viral shedding, which may increase the risk for resistance development, especially in cases of suboptimal exposure to antiviral therapy.201728205506
interim estimates of 2016-17 seasonal influenza vaccine effectiveness - united states, february 2017.in the united states, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). each influenza season since 2004-05, cdc has estimated the effectiveness of seasonal influenza vaccine to prevent influenza-associated, medically attended, acute respiratory illness (ari). this report uses data, as of february 4, 2017, from 3,144 children and adults enrolled in the u.s. influenza vaccine effectiveness network (u.s. flu ve network) during november 28, 2016-februa ...201728207689
distinct susceptibility and applicability of mdck derivatives for influenza virus research.madin-darby canine kidney (mdck) cells are widely utilized as a substrate for influenza virus isolation and propagation due to the high yields of virus. here we compared the conventional mdck cell line, mdck-siat1 and mdck-london for viral production, cell survival, and suitability in testing antivirals using six influenza strains including two h1n1 (pandemic and epidemic strains), three h3n2 and one influenza b strain. overall our results suggest that mdck-london cell line is superior for virus ...201728207898
novel multiplex assay platforms to detect influenza a hemagglutinin subtype-specific antibody responses for high-throughput and in-field applications.detections of influenza a subtype-specific antibody responses are often complicated by the presence of cross-reactive antibodies. we developed two novel multiplex platforms for antibody detection. the multiplexed magnetic fluorescence microsphere immunoassay (magpix) is a high-throughput laboratory-based assay. chembio dual path platform (dpp) is a portable and rapid test that could be used in the field.201728207986
safe recombinant outer membrane vesicles that display m2e elicit heterologous influenza protection.recombinant, escherichia coli-derived outer membrane vesicles (romvs), which display heterologous protein subunits, have potential as a vaccine adjuvant platform. one drawback to romvs is their lipopolysaccharide (lps) content, limiting their translatability to the clinic due to potential adverse effects. here, we explore a unique romv construct with structurally remodeled lipids containing only the lipid iva portion of lps, which does not stimulate human tlr4. the romvs are derived from a genet ...201728215994
a case of influenza a (h3n2) complicated by community-acquired pneumonia and death in a young healthy adult during the 2013-2014 season.with multiple available vaccines and antivirals, seasonal influenza a is typically a self-limited acutely debilitating illness in young healthy adults. here, we illustrate unexpected morbidity and mortality in a relatively young and healthy patient seen at a large tertiary care academic medical center for seasonal influenza a (h3n2) complicated by community-acquired pneumonia, hypoxic respiratory failure, septic shock, and death.201728229066
cryptoporic acid e from cryptoporus volvatus inhibits influenza virus replication in vitro.influenza virus infection is a global public health issue. the efficacy of antiviral agents for influenza virus has been limited by the emergence of drug-resistant virus strains. thus, there is an urgent need to identify novel antiviral therapies. our previous studies have found that cryptoporus volvatus extract can potently inhibit influenza virus replication in vitro and in vivo. however, the effective component of cryptoporus volvatus, which mediates the antiviral activity, hasn't been identi ...201728232246
viral co-infections among children with confirmed measles at hospitals in hanoi, vietnam, 2014.to characterize viral co-infections among representative hospitalized measles cases during the 2014 hanoi outbreak.201728237484
nasopharyngeal protein biomarkers of acute respiratory virus infection.infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. we sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with influenza a/h3n2 or human rhinovirus, and to develop targeted assays measuring peptides involved in this host response allowing classification of acute respiratory virus infection. unbiased proteomic discovery analysis identified 3285 peptides corr ...201728238698
comparison of influenza epidemiological and virological characteristics between outpatients and inpatients in zhejiang province, china, march 2011-june 2015.given the rapid rate of global spread and consequently healthcare costs related to influenza, surveillance plays an important role in monitoring the emerging pandemics in china. however, the characteristics of influenza in southeast of china haven't been fully studied. our study use the surveillance data collected from 16 sentinel hospitals across zhejiang province during march 2011 through june 2015, including the demographic information and respiratory specimens from influenza-like illness (il ...201728241447
triple-reassortant influenza a virus with h3 of human seasonal origin, na of swine origin, and internal a(h1n1) pandemic 2009 genes is established in danish pigs.this report describes a triple-reassortant influenza a virus with a ha that resembles h3 of human seasonal influenza from 2004 to 2005, n2 from influenza a virus already established in swine, and the internal gene cassette from a(h1n1)pdm09 has spread in danish pig herds. the virus has been detected in several danish pig herds during the last 2-3 years and may possess a challenge for human as well as animal health.201728245096
emergence of a novel subclade of influenza a(h3n2) virus in london, december 2016 to january 2017.we report the molecular investigations of a large influenza a(h3n2) outbreak, in a season characterised by sharp increase in influenza admissions since december 2016. analysis of haemagglutinin (ha) sequences demonstrated co-circulation of multiple clades (3c.3a, 3c.2a and 3c.2a1). most variants fell into a novel subclade (proposed as 3c.2a2); they possessed four unique amino acid substitutions in the ha protein and loss of a potential glycosylation site. these changes potentially modify the h3n ...201728251889
mid-season real-time estimates of seasonal influenza vaccine effectiveness in persons 65 years and older in register-based surveillance, stockholm county, sweden, and finland, january 2017.systems for register-based monitoring of vaccine effectiveness (ve) against laboratory-confirmed influenza (lci) in real time were set up in stockholm county, sweden, and finland, before start of the 2016/17 influenza season, using population-based cohort studies. both in stockholm and finland, an early epidemic of influenza a(h3n2) peaked in week 52, 2016. already during weeks 48 to 50, analyses of influenza ve in persons 65 years and above showed moderately good estimates of around 50%, then r ...201728251891
[pharmacoepidemiological study of the course of influenza and other acute respiratory viral infections in risk groups].to identify risk factors (rfs) for the development of bacterial complications and the prolonged course of influenza and other acute respiratory viral infections (arvis) among inpatients treated in russian healthcare facilities in the post-pandemic period; to determine the clinical presentation of the disease (flu-like syndrome) in risk-group people and to evaluate the efficacy of antiviral therapy with arbidol (umifenovir).201728252630
phylogenetic relationships of the ha and na genes between vaccine and seasonal influenza a(h3n2) strains in korea.seasonal influenza is caused by two influenza a subtype (h1n1 and h3n2) and two influenza b lineage (victoria and yamagata) viruses. of these antigenically distinct viruses, the h3n2 virus was consistently detected in substantial proportions in korea during the 2010/11-2013/14 seasons when compared to the other viruses and appeared responsible for the influenza-like illness rate peak during the first half of the 2011/12 season. to further scrutinize possible causes for this, we investigated the ...201728257427
molecular characterization of neuraminidase genes of influenza a(h3n2) viruses circulating in southwest india from 2009 to 2013.molecular characterization of neuraminidase (na) gene of 25 influenza a(h3n2) virus isolates (2009-2013) archived at the manipal centre for virus research was carried out. the annual rate of amino acid substitutions in the n2 gene of influenza a(h3n2) virus isolates was 0.2-0.6%. out of the 25 na sequences analyzed, catalytic site mutations were observed in three isolates. two of the mutations (d151g and e276g) were detected in functional catalytic residues, and an e227v mutation was detected in ...201728271163
serological response to trivalent inactivated influenza vaccine in hiv-infected adults in singapore.a cohort of 81 hiv-infected participants received seasonal trivalent inactivated influenza vaccine (tiv) and their humoral responses were monitored using hemagglutination inhibition (hai) assay and enzyme-linked immunosorbent assay (elisa). three weeks after the vaccination, the percentage of the cohort that had an hai titer of >1:40 was 35% (for h1n1), 43% (for h3n2) and 19% (for influenza b). an increase in hai titer can be achieved by an increase in magnitude of the antibody responses, which ...201728277090
generation of a live attenuated influenza vaccine that elicits broad protection in mice and ferrets.new influenza vaccines that provide effective and broad protection are desperately needed. live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. however, recent formulations of live attenuated influenza vaccines (laivs) have not been protective. we combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate w7-791, a live attenuated mutant virus strain. ...201728279345
prevention of influenza virus induced bacterial superinfection by standardized echinacea purpurea, via regulation of surface receptor expression in human bronchial epithelial cells.viral infections may predispose the airways to secondary bacterial infections that can lead to unfavorable progression of principally self-limiting illnesses. such complicated respiratory infections include pneumonia, bronchitis, sinusitis, acute otitis media, and sepsis, which cause high morbidity and lethality. some of the pathogenic consequences of viral infections, like the expression of bacterial adhesion receptors and the disturbance of physical barrier integrity due to inflammation, may c ...201728279802
h1n1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.a pandemic-capable influenza virus requires a hemagglutinin (ha) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. ha stabilization has been linked to 2009 ph1n1 pandemic potential in humans and h5n1 airborne transmissibility in the ferret model. swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on ha stability was unknown. for over 70 c ...201728282440
pathogenicity and transmission of triple reassortant h3n2 swine influenza a viruses is attenuated following turkey embryo propagation.genetic lineages of swine influenza a viruses (sivs) have recently been established in turkeys in the united states. to identify molecular determinants that are involved in virulence and transmission of sivs to turkeys, we sequentially passaged two triple reassortant h3n2 siv isolates from minnesota in ten day old specific-pathogen free (spf) turkey embryos and tested them in seven-day old turkey poults. we found that siv replication in turkey embryos led to minimal mutations in and around the r ...201728284612
a broadly reactive human anti-hemagglutinin stem monoclonal antibody that inhibits influenza a virus particle release.many broadly reactive human monoclonal antibodies against the hemagglutinin (ha) stem of influenza a virus have been developed for therapeutic applications. these antibodies typically inhibit viral entry steps, especially the ha conformational change that is required for membrane fusion. to better understand the mechanisms by which such antibodies inhibit viral replication, we established broadly reactive human anti-ha stem antibodies and determined the properties of these antibodies by examinin ...201728286060
quantitative proteomic approach identifies vpr binding protein as novel host factor supporting influenza a virus infections in human cells.influenza a virus infections are a major cause for respiratory disease in humans, which affects all age groups and contributes substantially to global morbidity and mortality. iav have a large natural host reservoir in avian species. however, many avian iav strains lack adaptation to other hosts and hardly propagate in humans. while seasonal or pandemic influenza a virus (iav) strains replicate efficiently in permissive human cells, many avian iav cause abortive non-productive infections in thes ...201728289176
in situ self-assembly of gold nanoparticles on hydrophilic and hydrophobic substrates for influenza virus-sensing platform.nanomaterials without chemical linkers or physical interactions that reside on a two-dimensional surface are attractive because of their electronic, optical and catalytic properties. an in situ method has been developed to fabricate gold nanoparticle (au np) films on different substrates, regardless of whether they are hydrophilic or hydrophobic surfaces, including glass, 96-well polystyrene plates, and polydimethylsiloxane (pdms). a mixture of sodium formate (hcoona) and chloroauric acid (haucl ...201728290527
a novel benzo-heterocyclic amine derivative n30 inhibits influenza virus replication by depression of inosine-5'-monophospate dehydrogenase activity.influenza virus is still a huge threat to the world-wide public health. host inosine-5'- monophosphate dehydrogenase (impdh) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative n30, which was designed to inhibit impdh.201728298229
cytokines induced during influenza virus infection.influenza a virus is one of the major human pathogens. the influenza infection can pass out without any subclinical symptoms or infestation can appear in upper respiratory tract as well as in lower respiratory tract where it can result in lethal outcome. both innate and adaptive immune responses are activated shortly after infection providing protection against infection. many activities of the cells of innate and adaptive immunity are coordinated by cytokines. however, inordinate or disbalanced ...201728302021
estimates of hospitalization attributable to influenza and rsv in the us during 1997-2009, by age and risk status.estimates of influenza and respiratory syncytial virus (rsv) burden must be periodically updated to inform public health strategies. we estimated seasonal influenza- and rsv-attributable hospitalizations in the us from 1997 to 2009 according to age and risk status (nct01599390).201728320361
poly-γ-glutamic acid/chitosan nanogel greatly enhances the efficacy and heterosubtypic cross-reactivity of h1n1 pandemic influenza vaccine.in 2009, the global outbreak of an influenza pandemic emphasized the need for an effective vaccine adjuvant. in this study, we examined the efficacy of poly-γ-glutamic acid/chitosan (pc) nanogel as an adjuvant for the influenza vaccine. pc nanogel significantly enhanced antigen-specific cross-presentation and cytotoxic t lymphocyte (ctl) activity. compared with alum, the protective efficacy of the pandemic h1n1 influenza (ph1n1) vaccine was substantially increased by pc nanogel, with increased h ...201728322289
characterization and mechanisms of anti-influenza virus metabolites isolated from the vietnamese medicinal plant polygonum chinense.polygonum chinense linn. is a common medicinal plant in southeast asia and has been used in traditional medicine in vietnam. the plant contains phytochemicals with various biological properties; however, its antiviral effect has not yet been demonstrated. this study was aimed to evaluate the anti-influenza virus activity of crude extracts of p. chinense, to characterize antiviral metabolites therefrom and to investigate their mechanisms of antiviral action.201728327126
heterologous packaging signals on ha, but not na or ns, limit influenza a virus reassortment.influenza a virus (iav) rna packaging signals serve to direct the incorporation of iav gene segments into virus particles, and this process is thought to be mediated by segment-segment interactions. these packaging signals are segment- and strain-specific, and as such, they have the potential to impact reassortment outcomes between different iav strains. our study aimed to quantify the impact of packaging signal mismatch on iav reassortment using the human seasonal influenza a/panama/2007/99 (h3 ...201728331085
neutralizing activities against seasonal influenza viruses in human intravenous immunoglobulin.influenza viruses a/h1n1, a/h3n2, and b are known seasonal viruses that undergo annual mutation. intravenous immunoglobulin (ivig) contains anti-seasonal influenza virus globulins. although the virus-neutralizing (vn) titer is an indicator of protective antibodies, changes in this titer over extended time periods have yet to be examined. in this study, variations in hemagglutination inhibition (hi) and vn titers against seasonal influenza viruses in ivig lots over extended time periods were exam ...201728331286
molecular characterization and phylogenetic analysis of human influenza a viruses isolated in iran during the 2014-2015 season.influenza a viruses are an important cause of severe infectious diseases in humans and are characterized by their fast evolution rate. global monitoring of these viruses is critical to detect newly emerging variants during annual epidemics. here, we sought to genetically characterize influenza a/h1n1pdm09 and a/h3n2 viruses collected in iran during the 2014-2015 influenza season. a total of 200 nasopharyngeal swabs were collected from patients with influenza-like illnesses. swabs were screened f ...201728331993
virological surveillance of influenza a subtypes isolated in 2014 from clinical outbreaks in canadian swine.influenza a viruses (iavs) are respiratory pathogens associated with an acute respiratory disease that occurs year-round in swine production. it is currently one of the most important pathogens in swine populations, with the potential to infect other host species including humans. ongoing research indicates that the three major subtypes of iav-h1n1, h1n2, and h3n2-continue to expand in their genetic and antigenic diversity. in this study, we conducted a comprehensive genomic analysis of 16 iavs ...201728335552
clinical and serologic responses after a two-dose series of high-dose influenza vaccine in plasma cell disorders: a prospective, single-arm trial.patients with multiple myeloma (mm) and other plasma cell disorders are highly susceptible to influenza infections, which are major causes of morbidity in this population, despite the routine administration of a seasonal influenza vaccination. existing data are limited by small and retrospective studies, which suggest poor seroprotection rates of < 20% after standard influenza vaccination in patients with mm.201728343904
characteristics of seasonal influenza a and b in latin america: influenza surveillance data from ten countries.the increased availability of influenza surveillance data in recent years justifies an actual and more complete overview of influenza epidemiology in latin america. we compared the influenza surveillance systems and assessed the epidemiology of influenza a and b, including the spatio-temporal patterns of influenza epidemics, in ten countries and sub-national regions in latin america.201728346498
[a prospective study to assess the burden of influenza-related hospitalizations and emergency department visits among children in bilbao, spain (2010-2011)].this study was undertaken to estimate the burden of morbidity associated with laboratory-confirmed influenza in children below 15 years of age.201728363360
dose sparing and lack of dose response relationship with an influenza vaccine in adult and elderly patients -a randomised, double-blind clinical trial.the currently licensed seasonal trivalent influenza vaccines contain 15 micrograms of hemagglutinin per strain for adult, and up to 60 micrograms for elderly patients. however, due to recent shortages, dose sparing to increase production capacity would be highly desirable. in the present study, we attempted to find a dose-response relationship for immunogenicity and thus, the optimal dose for seasonal influenza vaccines in adult and elderly patients.201728378403
discovery of acylguanidine oseltamivir carboxylate derivatives as potent neuraminidase inhibitors.in search of novel anti-influenza agents with higher potency, a series of acylguanidine oseltamivir carboxylate analogues were synthesized and evaluated against influenza viruses (h1n1 and h3n2) in vitro. the representative compounds with strong inhibitory activities (ic50 <40nm) against neuraminidase (na) were further tested against the na from oseltamivir-resistant strain (h259y). among them, compounds 9 and 17 were potent na inhibitors that exhibited a 5 and 11-fold increase in activity compa ...201728385598
immunogenicity and safety of a quadrivalent inactivated influenza virus vaccine compared with a comparator quadrivalent inactivated influenza vaccine in a pediatric population: a phase 3, randomized noninferiority study.seqirus 2010 southern hemisphere split-virion trivalent inactivated influenza vaccine (iiv3) was associated with increased febrile reactions in children. studies in vitro concluded that increasing concentrations of splitting agent decreased residual lipids and attenuated proinflammatory cytokine signals associated with fever. we assessed immunogenicity and safety of a quadrivalent inactivated influenza vaccine (iiv4; produced using higher concentration of splitting agent) versus a united states- ...201728390934
vaccination with killed but metabolically active e. coli over-expressing hemagglutinin elicits neutralizing antibodies to h1n1 swine origin influenza a virus.there is a need for a fast and simple method for vaccine production to keep up with the pace of a rapidly spreading virus in the early phases of the influenza pandemic. the use of whole viruses produced in chicken eggs or recombinant antigens purified from various expression systems has presented considerable challenges, especially with lengthy processing times. here, we use the killed but metabolically active (kbma) escherichia coli (e. coli) to harbor the hemagglutinin (ha) of swine origin inf ...201728492063
antiviral activity of phenanthrenes from the medicinal plant bletilla striata against influenza a virus.influenza represents a serious public health concern. the emergence of resistance to anti-influenza drugs underlines the need to develop new drugs. this study aimed to evaluate the anti-influenza viral activity and possible mechanisms of 12 phenanthrenes from the medicinal plant bletilla striata (orchidaceae family).201728532402
[impact of mutations in nucleoprotein on replication of influenza virus a/hong kong/1/68/162/35 reassortants at different temperatures].the nucleoprotein (np) of influenza virus is a multifunctional rna binding protein. the role of np in the adaptation of influenza viruses to a host has been experimentally proved. ambiguous data are available on the role of nucleoprotein in the attenuation of influenza a viruses, which is characterized by ability to replicate at low temperature (26°c) and inability to replicate at high temperature (39°c). influenza virus donor strain a/hong kong/1/68/162/35 (h3n2), adapted to growth at low tempe ...201728537245
seasonal h3n2 and 2009 pandemic h1n1 influenza a viruses reassort efficiently but produce attenuated progeny.reassortment of gene segments between coinfecting influenza a viruses (iavs) facilitates viral diversification and has a significant epidemiological impact on seasonal and pandemic influenza. since 1977, human iavs of h1n1 and h3n2 subtypes have cocirculated with relatively few documented cases of reassortment. we evaluated the potential for viruses of the 2009 pandemic h1n1 (ph1n1) and seasonal h3n2 lineages to reassort under experimental conditions. results of heterologous coinfections with ph ...201728637755
molecular epidemiology of a novel re-assorted epidemic strain of equine influenza virus in pakistan in 2015-16.a widespread epidemic of equine influenza (ei) occurred in nonvaccinated equine population across multiple districts in khyber pakhtunkhwa province of pakistan during 2015-2016.201728757141
mutation signature in neuraminidase gene of avian influenza h9n2/g1 in egypt.the low pathogenic avian influenza (lpai) h9n2 subtype has become the most prevalent and widespread in many asian and middle eastern countries. it causes an enzootic situation in commercial poultry and known as a potential facilitator virus that can be transmitted to human from birds. the neuraminidase (na) gene plays an important role the release and spread of the virus from infected cells and throughout the bird. the complete nucleotide sequences of the na gene of seven h9n2 viruses collected ...201728770242
cross-reactive influenza-specific antibody-dependent cellular cytotoxicity-mediating antibodies in hiv-infected indian individuals.the influenza-specific antibodies mediating antibody-dependent cellular cytotoxicity (adcc) may be important in protection against influenza. however, it is not known whether immunocompromised individuals such as hiv-infected persons who have never been vaccinated with influenza vaccine have such a response.201728776433
infection of ferrets with influenza virus elicits a light chain-biased antibody response against hemagglutinin.the domestic ferret (mustela putorius furo) is a commonly used animal model for the study of influenza virus infection and vaccination. recently, our group has developed murine mabs with specificity for the κ (igκ) and λ (igλ) l chains of ferret ig. these mabs were used to quantify the abundance of igκ and igλ in serum and to evaluate l chain usage of the ab response against the hemagglutinin (ha) protein elicited by influenza infection. after influenza a infection of immunologically naive ferre ...201729079697
colocalization of intracellular specific iga (iciga) with influenza virus in patients' nasopharyngeal aspirate cells.inhibition of viral replication by iciga antibodies has only been observed with in vitro studies using epithelial cell lines in transwell cultures. this effect appears to involve an interaction between polymeric immunoglobulin a (piga) and viral particles within an intracellular compartment, since iga is transported across polarized cells. polyclonal guinea pig antisera against purified influenza a virus and mouse antisera prepared against influenza a/h3n2 hemagglutinin (ha0) cleavage loop pepti ...201829102516
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