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amino acids in hemagglutinin antigenic site b determine antigenic and receptor binding differences between a(h3n2)v and ancestral seasonal h3n2 influenza viruses.influenza a h3n2 variant [a(h3n2)v] viruses, which have caused human infections in the united states in recent years, originated from human seasonal h3n2 viruses that were introduced into north american swine in the mid-1990s, but they are antigenically distinct from both the ancestral and current circulating h3n2 strains. a reference a(h3n2)v virus, a/minnesota/11/2010 (mn/10), and a seasonal h3n2 strain, a/beijing/32/1992 (bj/92), were chosen to determine the molecular basis for the antigenic ...201727807224
comparative analysis of influenza a(h3n2) virus hemagglutinin specific igg subclass and iga responses in children and adults after influenza vaccination.two different influenza vaccines are generally used in many countries; trivalent live attenuated influenza vaccine (laiv3) and trivalent inactivated influenza vaccine (iiv3). studies comparing the antibody response to iiv3 and laiv3 commonly investigate the seroprotective response by hemagglutination-inhibition (hi) assay. however, there is limited data regarding comparative analysis of igg subclass and iga responses induced by laiv3 and iiv3. fifteen children <5years received 2 doses of laiv3 w ...201727789145
in vitro exposure system for study of aerosolized influenza virus.infection of adherent cell monolayers using a liquid inoculum represents an established method to reliably and quantitatively study virus infection, but poorly recapitulates the exposure and infection of cells in the respiratory tract that occurs during infection with aerosolized pathogens. to better simulate natural infection in vitro, we adapted a system that generates viral aerosols similar to those exhaled by infected humans to the inoculation of epithelial cell monolayers. procedures for ce ...201727771560
an early innate response underlies severe influenza-induced exacerbations of asthma in a novel steroid-insensitive and anti-il-5-responsive mouse model.acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. the lack of an adequate animal model hampers mechanistic insight and the development of new therapeutics.201727696462
correction: accelerating influenza research: vaccines, antivirals, immunomodulators and monoclonal antibodies. the manufacture of a new wild-type h3n2 virus for the human viral challenge model.[this corrects the article doi: 10.1371/journal.pone.0145902.].201727280602
a pyrosequencing-based approach to high-throughput identification of influenza a(h3n2) virus clades harboring antigenic drift variants.the rapid evolution of influenza a(h3n2) viruses necessitates close monitoring of their antigenic properties so the emergence and spread of antigenic drift variants can be rapidly identified. changes in hemagglutinin (ha) acquired by contemporary a(h3n2) viruses hinder antigenic characterization by traditional methods, thus complicating vaccine strain selection. sequence-based approaches have been used to infer virus antigenicity; however, they are time consuming and mid-throughput. to facilitat ...201727795346
molecular and antigenic characterization of the h3 hemagglutinin of h3n2 influenza a virus strains collected in the czech republic during the 2014/2015 epidemic season.the 2014/2015 influenza epidemic season was characterized by the predominance of the h3n2 subtype. the presented study investigated the genetic and antigenic heterogeneity of the h3n2 strains collected in the czech republic from november 2014 to march 2015. phylogenetic analysis of the representative h3 hemagglutinin sequences was performed and the glycosylation status and crucial antigenic mutations were compared relative to the 2014 and 2015 vaccine strains (a/texas/50/2012 and a/switzerland/9 ...201727467326
clinical characteristics and factors associated with severe acute respiratory infection and influenza among children in jingzhou, china.influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory-confirmed influenza in china.201727465959
hospital surveillance of influenza strains: a concordant image of viruses identified by the swiss sentinel system?the swiss sentinel system for influenza virus surveillance reports influenza-like illness in the community through a network of primary care practitioners, but the epidemiologic, demographic, and virological characterization may differ from that observed in hospitalized patients with influenza.201727441401
[excess mortality associated with influenza in spain in winter 2012].an excess of mortality was detected in spain in february and march 2012 by the spanish daily mortality surveillance system and the «european monitoring of excess mortality for public health action» program. the objective of this article was to determine whether this excess could be attributed to influenza in this period.201725770916
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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 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
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
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
temperature-sensitive live-attenuated canine influenza virus h3n8 vaccine.canine influenza is a respiratory disease of dogs caused by canine influenza virus (civ). civ subtypes responsible for influenza in dogs include h3n8, which originated from the transfer of h3n8 equine influenza virus to dogs; and the h3n2 civ, which is an avian-origin virus that adapted to infect dogs. influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. currently, only inactivated influenza vaccines (iivs) are available for the pre ...201727928017
identification of inonotus obliquus polysaccharide with broad-spectrum antiviral activity against multi-feline viruses.inonotus obliquus polysaccharides (iops) are a potential drug for the prevention and treatment of cancer, cardiopathy, diabetes, aids, pancreatitis and other diseases. in this study, we found that iop can act as a broad-spectrum antiviral drug against feline viruses in the in vitro experiment. using cell models of feline calicivirus (fcv), we demonstrated that iop treatment was capable of exhibiting anti-fcv strain f9 activity in cell-based assays and also showed low cytotoxicity. investigation ...201727865960
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
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
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
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
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
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
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
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
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
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
versatility of a localized surface plasmon resonance-based gold nanoparticle-alloyed quantum dot nanobiosensor for immunofluorescence detection of viruses.flu infection, caused by the influenza virus, constitutes a serious threat to human lives worldwide. a rapid, sensitive and specific diagnosis is urgently needed for point-of-care treatment and to control the rapid spread of this disease. in this study, an ultrasensitive, rapid and specific localized surface plasmon resonance (lspr)-induced immunofluorescence nanobiosensor has been developed for the influenza virus based on a gold nanoparticle (aunp)-induced quantum dot (qd) fluorescence signal. ...201727825520
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
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
performance evaluation of allplex respiratory panels 1, 2, and 3 for detection of respiratory viruses and influenza a virus subtypes.the allplex respiratory panels 1, 2, and 3 (allplex) comprise a one-step real-time reverse transcription-pcr assay for the detection of respiratory viruses (rvs) and influenza a subtypes based on multiple detection temperature (mudt) technology. the performance of the allplex assay was compared with those of the advansure rv real-time pcr kit (advansure) and the powerchek pandemic h1n1/h3n2/h5n1 real-time pcr kit (powerchek) using 417 clinical respiratory specimens. in comparison with the advans ...201727903601
origin, distribution, and potential risk factors associated with influenza a virus in swine in two production systems in guatemala.guatemala is the country with the largest swine production in central america; however, evidence of influenza a virus (iav) in pigs has not been clearly delineated.201727860313
generation and characterisation of monoclonal antibodies specific to avian influenza h7n9 haemagglutinin protein.emerging virulent strains of influenza virus pose a serious public health threat with potential pandemic consequences. a novel avian influenza virus, h7n9, breached the species barrier from infected domestic poultry to humans in 2013 in china. since then, it has caused numerous infections in humans with a close contact to poultry.201727934828
reassortment between swine h3n2 and 2009 pandemic h1n1 in the united states resulted in influenza a viruses with diverse genetic constellations with variable virulence in pigs.repeated spillovers of the h1n1 pandemic virus (h1n1pdm09) from humans to pigs resulted in substantial evolution of influenza a viruses infecting swine, contributing to the genetic and antigenic diversity of influenza a viruses (iav) currently circulating in swine. the reassortment with endemic swine viruses and maintenance of some of the h1n1pdm09 internal genes resulted in the circulation of different genomic constellations in pigs. here, we performed a whole-genome phylogenetic analysis of 36 ...201727928015
immunity against influenza a(h1n1) infections is determined by age at the time of initial strain circulation.we explored age-dependent patterns in haemagglutination inhibition (hi) titre to seasonal [1956 a(h1n1), 1977 a(h1n1), 2007 a(h1n1)] and pandemic [a(h1n1)pdm09] influenza strains using serological data collected from an adult french influenza cohort. subjects were recruited by their general practitioners from 2008 to 2009 and followed until 2010. we explored age-related differences between strain-specific hi titres using 1053 serological samples collected over the study period from 398 unvaccina ...201727682472
sensitive detection and simultaneous discrimination of influenza a and b viruses in nasopharyngeal swabs in a single assay using next-generation sequencing-based diagnostics.reassortment of 2009 (h1n1) pandemic influenza virus (pdh1n1) with other strains may produce more virulent and pathogenic forms, detection and their rapid characterization is critical. in this study, we reported a "one-size-fits-all" approach using a next-generation sequencing (ngs) detection platform to extensively identify influenza viral genomes for diagnosis and determination of novel virulence and drug resistance markers. a de novo module and other bioinformatics tools were used to generate ...201727658193
reassortment of high-yield influenza viruses in vero cells and safety assessment as candidate vaccine strains.vaccination is the practiced and accessible measure for preventing influenza infection. because chicken embryos used for vaccine production have various insufficiencies, more efficient methods are needed. african green monkey kidney (vero) cells are recommended by the world health organization (who) as a safe substitute for influenza vaccine production for humans. however, the influenza virus usually had low-yield in vero cells, which limits the usage of vero cellular vaccines. this study used 2 ...201727648636
influenza in children.in children, influenza is one among the commonest causes of acute respiratory illness and loss of school days. influenza a, b, and c are 3 types of viruses responsible for illness. type a virus has many subtypes based on antigens but type b and type c viruses have no known subtypes. currently, influenza a/h1n1, a/h3n2, and influenza type b viruses are circulating in humans. transmission of influenza occurs through droplets from infected person or through direct contact with person or fomites. cl ...201727641976
drug-resistant and genetic evolutionary analysis of influenza virus from patients during the 2013 and 2014 influenza season in beijing.the study aimed to analyze drug resistance and mutations and genetic evolution of influenza a and influenza b viruses during the 2013 and 2014 influenza season in beijing, china. rna was extracted from pharyngeal or nasal swabs of 28 patients, and determination of influenza genotypes was performed by using real-time reverse-transcription polymerase chain reaction. influenza a virus samples were sequenced with the neuraminidase (na) gene and m2 matrix protein gene to determine the na inhibitor (n ...201727203354
impact of a large deletion in the neuraminidase protein identified in a laninamivir-selected influenza a/brisbane/10/2007 (h3n2) variant on viral fitness in vitro and in ferrets.viral fitness of a laninamivir-selected influenza a/brisbane/10/2007-like (h3n2) isolate (lrvp9) containing a 237-amino acid neuraminidase deletion and a p194l hemagglutinin mutation was evaluated in vitro and in ferrets. lrvp9 and the wild-type (wt) virus showed comparable replication kinetics in mdck-st6gali cells. cultured virus was recovered between days 2 and 5 post-infection in nasal washes (nw) from the 4 wt-infected ferrets whereas no virus was recovered from the lrvp9-infected animals. ...201626526406
human micrornas profiling in response to influenza a viruses (subtypes ph1n1, h3n2, and h5n1).micrornas (mirnas) play an important role in regulation of gene silencing and are involved in many cellular processes including inhibition of infected viral replication. this study investigated cellular mirna expression profiles operating in response to influenza virus in early stage of infection which might be useful for understanding and control of viral infection. a549 cells were infected with different subtypes of influenza virus (ph1n1, h3n2 and h5n1). after 24 h post-infection, mirnas were ...201626518627
differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge.exposure to influenza virus triggers a complex cascade of events in the human host. in order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza a/wisconsin/67/2005 (h3n2), and then had serial peripheral blood samples drawn and tested for the presence of 25 major human cytokines. nine of 17 (53%) inoculated subjects developed symptomatic influenza infection. individuals who will go on to become symptomatic demonstrate inc ...201626506932
antigenic maps of influenza a(h3n2) produced with human antisera obtained after primary infection.antigenic characterization of influenza viruses is typically based on hemagglutination inhibition (hi) assay data for viral isolates tested against strain-specific postinfection ferret antisera. here, similar virus characterizations were performed using serological data from humans with primary influenza a(h3n2) infection.201626142433
the clinical usefulness of lymphocyte:monocyte ratios in differentiating influenza from viral non-influenza-like illnesses in hospitalized adults during the 2015 influenza a (h3n2) epidemic: the uniqueness of hpiv-3 mimicking influenza a.during influenza epidemics, influenza-like illnesses (ilis) viruses cocirculate with influenza strains. if positive, rapid influenza diagnostic tests (ridts) identify influenza a/b, but false-negative ridts require retesting by viral polymerase chain reaction (pcr). patient volume limits testing during influenza epidemics, and non-specific laboratory findings have been used for presumptive diagnosis pending definitive viral testing. in adults, the most useful laboratory abnormalities in influenz ...201626563893
[ph-dependent rearrangements in the influenza a virus].the influenza virus possesses two modules: internal ribonucleoprotein (rnp) containing the viral genome rna and external lipid envelope with transmembrane ionic channel protein m2 and embedded glycoproteins hemagglutinin (ha) and neuraminidase (na) forming surface spike ends. these modules are combined in a whole virion by the matrix protein m1. the effect of the acidic ph 4,2-4,5 on the influenza virus grown in mdck-h cells was tested. the a/aichi/68 (h3n2) virus synthesized in mdck-h cells was ...201625335418
[immunization with live attenuated a/h5n1 vaccine protects guinea pigs from reinfection].cold-adapted influenza virus a/hk/1/68/162/35(h3n2) was developed as unified donor of attenuation and high reproductive capacity forvaccine strains. the reassortant of this donor with surface antigens of highly pathogenic strain alchicken/astana/6/05 (h5n1) was tested in guinea pigs as a live or inactivated preparation. immunization with both formulations induced equal levels of serum virus specific antibodies, while the level of mucosal antibodies was significantly higher in animals immunized w ...201624772645
[evolution of influenza a(h3n2) virus from 2007 to 2012].the results of the genetic studies of influenza viruses make it possible to understand their evolution and recommendations for vaccine strains content. in this work, the data of complete sequence of the ha, na, and m2-protein for 34 strains of influenza a(h3n2) virus circulating in russia during 2007-2012 are presented. the influenza strains were isolated in ivanovsky institute of virology, moscow, and some collaborating russian centers. the results of the phylogenetic analysis showed the differ ...201624772643
one-health simulation modelling: a case study of influenza spread between human and swine populations using naadsm.the circulation of zoonotic influenza a viruses including ph1n1 2009 and h5n1 continue to present a constant threat to animal and human populations. recently, an h3n2 variant spread from pigs to humans and between humans in limited numbers. accordingly, this research investigated a range of scenarios of the transmission dynamics of ph1n1 2009 virus at the swine-human interface while accounting for different percentages of swine workers initially immune. furthermore, the feasibility of using naad ...201624661802
the rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model.dendritic cells (dcs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. the aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (lalns) in the model of a non-human primate (nhp) infected by influenza a virus (iav). cynomolgus macaques were infected with influenza a virus (h3n2) via bronchosco ...201624780366
seroepidemiological evidence of subtype h3n8 influenza virus infection among pet dogs in china.the h3n8 virus and the h3n2 virus are the main subtypes of canine influenza virus (civ). h3n8 civ mainly circulates in america, and h3n2 civ mainly circulates in asia. however, there was an outbreak of the asian h3n2 virus in the united states (us) in 2015. thus, it is important to evaluate the presence of subtype h3n8 virus in dogs in china. from may 2015 to november 2015, 600 sera from pet dogs were collected from guangzhou, shanghai, beijing and shenzhen for hemagglutination inhibition (hi) a ...201627414031
persistent infection of drug-resistant influenza a virus during chemotherapy for malignant lymphoma.we herein report the case of an 80-year-old man with malignant lymphoma who became persistently infected with influenza a virus. although he was repeatedly treated with na inhibitors, such as oseltamivir or peramivir, nasal cavity swab tests for influenza a antigen continued to be positive for more than 2 months. virological analyses revealed that he was infected with the na inhibitor-resistant a (h3n2) virus possessing an r292k substitution in the na protein. these findings suggest that a drug- ...201627374689
influenza vaccine effectiveness against antigenically drifted influenza higher than expected in hospitalized adults: 2014-2015.the 2014-2015 influenza season was severe, with circulating influenza a (h3n2) viruses that were antigenically drifted from the vaccine virus. reported vaccine effectiveness (ve) estimates from ambulatory care settings were markedly decreased.201627369320
in vitro neuraminidase inhibitory concentration (ic50) of four neuraminidase inhibitors against clinical isolates of the influenza viruses circulating in the 2010-2011 to 2014-2015 japanese influenza seasons.to assess the extent of viral resistance to the four neuraminidase inhibitors (nais), we measured their 50% inhibitory concentration (ic50) for influenza virus isolates from the 2014-2015 influenza season for comparison with those circulating in the 2010-2011 to 2013-2014 influenza seasons. viral isolation was done with specimens obtained prior to treatment, and the type and subtype of influenza was determined by rt-pcr using type- and subtype-specific primers. the ic50 was determined by a neura ...201627346379
oseltamivir resistance in an influenza a (h3n2) virus isolated from an immunocompromised patient during the 2014-2015 influenza season in alberta, canada.this manuscript describes the identification of an oseltamivir-resistant influenza a (h3n2) virus in a respiratory specimen collected from an immunocompromised patient in alberta, canada, during the 2014-2015 influenza season. following treatment with oseltamivir, neuraminidase (na) gene sequencing indicated the presence of an r292k mutation. phenotypic susceptibility testing by the na-star assay indicated a highly reduced inhibition by oseltamivir and normal inhibition by zanamivir. the use of ...201627442795
deep sequencing of influenza a virus from a human challenge study reveals a selective bottleneck and only limited intrahost genetic diversification.knowledge of influenza virus evolution at the point of transmission and at the intrahost level remains limited, particularly for human hosts. here, we analyze a unique viral data set of next-generation sequencing (ngs) samples generated from a human influenza challenge study wherein 17 healthy subjects were inoculated with cell- and egg-passaged virus. nasal wash samples collected from 7 of these subjects were successfully deep sequenced. from these, we characterized changes in the subjects' vir ...201627707932
effects of repeated annual inactivated influenza vaccination among healthcare personnel on serum hemagglutinin inhibition antibody response to a/perth/16/2009 (h3n2)-like virus during 2010-11.recently, lower estimates of influenza vaccine effectiveness (ve) against a(h3n2) virus illness among those vaccinated during the previous season or multiple seasons have been reported; however, it is unclear whether these effects are due to differences in immunogenicity.201626813801
molecular analyses of h3n2 canine influenza viruses isolated from korea during 2013-2014.canine influenza a virus (civ) causes a respiratory disease among dog populations and is prevalent in north america and asia. recently, asian h3n2 civ infection has been of particular concern, with recent reports related to reassortants with pandemic 2009 strains, direct transmission from a human h3n2, a possibility of h3n2 civ transmission to other mammals, and even the first outbreak of h3n2 civs in north america in april 2015. however, despite these global concerns, our understanding of how i ...201626810402
influenza virus shedding in laninamivir-treated children upon returning to school.the current school health and safety act in japan states that children with influenza infection should stay home until day 6(th) after symptoms onset. this was an amendment of a previous version recommending school return on day 3 after defervescence. here, we investigated the duration of fever and virus shedding after laninamivir treatment in 7 children infected with influenza a(h3n2) virus and 21 children with influenza b virus in relation to the school return timing recommended by the school ...201626806610
new potent sars-cov 3c-like protease inhibitors derived from thieno[2,3-d]-pyrimidine derivatives.2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1) condensed with carbaldehydes 2a,b to give the respective thienopyrimidines (3a,b), which reacted with phosphoryl chloride and hydrazine hydrate to afford the respective pyrimidinohydrazines (4a,b). compound 4a condensed with acetophenone under vilsmeier conditions to afford the formylated pyrazolopyrimidine 6. condensation of 4a with active methylenes produced the respective pyrazolopyrimidines (7-11). besides, 4a condensed with succi ...201626806115
human nasal epithelial cells derived from multiple subjects exhibit differential responses to h3n2 influenza virus infection in vitro. 201626806046
incidence and clinical course of respiratory viral coinfections in children aged 0-59 months.clinical data available on coinfections are contradictory concerning both the number of viruses involved and the severity of the condition. a total of 114 patients aged 0-59 months with symptoms of respiratory tract infection were enrolled into the study. nasal and pharyngeal swabs were tested using the pcr method for the following 12 viruses: influenza a, influenza b, respiratory syncytial virus a (rsv a), respiratory syncytial virus b (rsv b), adenovirus, metapneumovirus, coronavirus 229e/nl63 ...201626801151
antibiotic prescription practices among children with influenza.the important factor in the development of resistance to antibiotics is their overuse, especially for viral respiratory infections. the aim of the study was to find out the frequency of the antibiotic therapy administrated to children with influenza. a total of 114 children younger than 59 months seeking care for the acute respiratory tract infection was enrolled into the study. the patients had influenza-like symptoms: fever > 38 °c, cough, and sore throat of less than 4 days duration. nasal an ...201626801146
the semi-synthesis of novel andrographolide analogues and anti-influenza virus activity evaluation of their derivatives.two novel andrographolide analogues with the structural motif of δ(8,17)-alkene exo-to-endo isomerization, ai78 and ai89, were semi-synthesized firstly. two series of derivatives were designed and synthesized based on the synthetic pathway (including series i: olefin isomerizing to endocyclic δ(8,9) and series ii: olefin isomerizing to endocyclic δ(7,8)). the anti-influenza virus activity in vitro for all derivatives was evaluated. among the compounds synthesized, compound 38 with benzyl amino g ...201626791013
ultrasensitive detection of influenza viruses with a glycan-based impedimetric biosensor.an ultrasensitive impedimetric glycan-based biosensor for reliable and selective detection of inactivated, but intact influenza viruses h3n2 was developed. such glycan-based approach has a distinct advantage over antibody-based detection of influenza viruses since glycans are natural viral receptors with a possibility to selectively distinguish between potentially pathogenic influenza subtypes by the glycan-based biosensors. build-up of the biosensor was carefully optimized with atomic force mic ...201626765527
correlates of protection against influenza in the elderly: results from an influenza vaccine efficacy trial.although a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. a recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired a/h3n2 influenza illness. the high- ...201626762363
isolation of a novel h3n2 influenza virus containing a gene of h9n2 avian influenza in a dog in south korea in 2015.we isolated a serotype h3n2 influenza virus from a dog with severe respiratory distress in an animal clinic in south korea in 2015 and characterized the sequences of its eight genes. the following seven genes were derived from canine influenza virus: pb2, pb1, ha, np, na, m, and ns. however, the pa gene was derived from avian h9n2 influenza virus that is circulating in poultry in korea. these findings suggest that the continued surveillance of the influenza virus in dogs is warranted because hum ...201626757941
targeting host calpain proteases decreases influenza a virus infection.influenza a viruses (iav) trigger contagious acute respiratory diseases. a better understanding of the molecular mechanisms of iav pathogenesis and host immune responses is required for the development of more efficient treatments of severe influenza. calpains are intracellular proteases that participate in diverse cellular responses, including inflammation. here, we used in vitro and in vivo approaches to investigate the role of calpain signaling in iav pathogenesis. calpain expression and acti ...201626747784
multiplex rt-pcr detection of h3n2 influenza a virus in dogs.a multiplex rt-pcr (mrt-pcr) assay to detect h3n2 civ genomic segments was developed as a rapid and cost-effective method. its performance was evaluated with forty-six influenza a viruses from different hosts using three primer sets which amplify four segments of h3n2 civ simultaneously. the mrt-pcr has been successful in detecting the viral segments, indicating that it can improve the speed of diagnosis for h3n2 civ and its reassortants.201626738688
identification of the ifn-β response in h3n2 canine influenza virus infection.canine influenza viruses (civs) circulate continuously in the dog population, providing opportunities for exposure to humans and other species. although the dog genome has been sequenced, innate immunity in dogs is not well characterized, which limits the understanding of h3n2 canine influenza virus pathogenesis. equally, how this virus evades the canine host innate immune response to successfully establish infection remains unclear. to analyse the ifn-β response to civ infection in madin-darby ...201626490006
ineffectiveness of the 2014-2015 h3n2 influenza vaccine.the seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. nasopharyngeal samples of vaccinated and non-vaccinated patients presenting with influenza-like-illness (ili) were collected from over 20 outpatient clinics located in different geographic parts of israel and were tested for the presence of influenza viruses (influenza a and influenza b). here we show, that in the 2014-2015 season, the vaccine that included the a/texas/50/2012 h3n2 vir ...201626716420
outcomes of influenza infections in hematopoietic cell transplant recipients: application of an immunodeficiency scoring index.hematopoietic cell transplant (hct) recipients have lower immune response to influenza vaccination and are susceptible to lower respiratory tract infection (lri) and death. we determined clinical characteristics and outcomes of laboratory-confirmed influenza, including 2014/h3n2 infection, in 146 hct recipients. an immunodeficiency scoring index (isi) was applied to identify patients at high risk for lri and death. thirty-three patients (23%) developed lri and 7 (5%) died within 30 days of diagn ...201626638804
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