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analytical sensitivity comparison between singleplex real-time pcr and a multiplex pcr platform for detecting respiratory viruses.multiplex pcr methods are attractive to clinical laboratories wanting to broaden their detection of respiratory viral pathogens in clinical specimens. however, multiplexed assays must be well optimized to retain or improve upon the analytic sensitivity of their singleplex counterparts. in this experiment, the lower limit of detection (lod) of singleplex real-time pcr assays targeting respiratory viruses is compared to an equivalent panel on a multiplex pcr platform, the genmark esensor rvp. lods ...201526569120
partial protection induced by 2011-2012 influenza vaccine against serologically evidenced a(h3n2) influenza virus infections in elderly institutionalized people.ninety-two institutionalized elderly subjects were vaccinated with trivalent influenza inactivated vaccine available for the 2011-2012 season, characterized by a prevalent circulation of a(h3n2) influenza viruses (a/victoria/208-clade) presenting antigenic and genetic patterns different from the a(h3n2) vaccine component (a/perth/16/2009-clade). haemagglutination inhibiting (hi) antibody titers were determined in sera collected before, 1 and 6 months after vaccination and patients were considere ...201626577530
surveillance for severe acute respiratory infections in southern arizona, 2010-2014.the binational border infectious disease surveillance program began surveillance for severe acute respiratory infections (sari) on the us-mexico border in 2009. here, we describe patients in southern arizona.201626590069
natural co-infection of influenza a/h3n2 and a/h1n1pdm09 viruses resulting in a reassortant a/h3n2 virus.despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. these co-infections can result in the emergence of reassortant progeny.201526590689
identification of a small-molecule inhibitor of influenza virus via disrupting the subunits interaction of the viral polymerase.assembly of the heterotrimeric influenza virus polymerase complex from the individual subunits pb1, pa, and pb2 is a prerequisite for viral replication, in which the interaction between the c terminal of pa (pac) and the n-terminal of pb1 (pb1n) may be a desired target for antiviral development. in this study, we compared the feasibility of high throughput screening by enzyme-linked immunosorbent assay (elisa) and fluorescence polarization assay. among the two, elisa was demonstrated to own broa ...201626593979
substantial influenza vaccine effectiveness in households with children during the 2013-2014 influenza season, when 2009 pandemic influenza a(h1n1) virus predominated.we examined the influenza vaccine effectiveness (ve) during the 2013-2014 influenza season, in which 2009 pandemic influenza a(h1n1) virus (influenza a[h1n1]pdm09) predominated. in 2 previous years when influenza a(h3n2) virus predominated, the ve was low and negatively affected by prior year vaccination.201626597255
zanamivir-resistant influenza viruses with q136k or q136r neuraminidase residue mutations can arise during mdck cell culture creating challenges for antiviral susceptibility monitoring.surveillance of circulating influenza strains for antiviral susceptibility is important to ensure patient treatment guidelines remain appropriate. influenza a(h3n2) and a(h1n1)pdm09 virus isolates containing mutations at the q136 residue of the neuraminidase (na) that conferred reduced susceptibility to the na inhibitor (nai) zanamivir were detected during antiviral susceptibility monitoring. interestingly, the mutations were not detectable in the viruses from respective clinical specimens, only ...201526608955
labdisk with complete reagent prestorage for sample-to-answer nucleic acid based detection of respiratory pathogens verified with influenza a h3n2 virus.portable point-of-care devices for pathogen detection require easy, minimal and user-friendly handling steps and need to have the same diagnostic performance compared to centralized laboratories. in this work we present a fully automated sample-to-answer detection of influenza a h3n2 virus in a centrifugal labdisk with complete prestorage of reagents. thus, the initial supply of the sample remains the only manual handling step. the self-contained labdisk automates by centrifugal microfluidics al ...201626610171
assessment of influenza vaccine effectiveness in a sentinel surveillance network 2010-13, united states.influenza vaccines are now widely used to reduce the burden of annual epidemics of influenza virus infections. influenza vaccine effectiveness (ve) is monitored annually to determine ve against each season's circulating influenza strains in different groups such as children, adults and the elderly. few prospective surveillance programs are available to evaluate influenza ve against medically attended illness for patients of all ages in the united states.201626611200
prediction of the next highly pathogenic avian influenza pandemic that can cause illness in humans.in recent years, avian influenza viruses (aivs) have seriously threatened human health. questions such as: why do aivs infect humans?, how quickly can an aiv become pandemic?, and which virus is the most dangerous? cannot be sufficiently answered using current bioinformatic studies.201526612517
distinct functional determinants of influenza hemagglutinin-mediated membrane fusion.membrane fusion is the critical step for infectious cell penetration by enveloped viruses. we have previously used single-virion measurements of fusion kinetics to study the molecular mechanism of influenza-virus envelope fusion. published data on fusion inhibition by antibodies to the 'stem' of influenza virus hemagglutinin (ha) now allow us to incorporate into simulations the provision that some has are inactive. we find that more than half of the has are unproductive even for virions with no ...201526613408
genome-wide analysis of evolutionary markers of human influenza a(h1n1)pdm09 and a(h3n2) viruses may guide selection of vaccine strain candidates.here we analyzed whole-genome sequences of 3,969 influenza a(h1n1)pdm09 and 4,774 a(h3n2) strains that circulated during 2009-2015 in the world. the analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza a(h1n1)pdm09 and a(h3n2) strains, respectively. many of these changes were introduced as a result of random drift. however, there were 61 and 68 changes that were present in relatively large number of a(h1n1)pdm09 and a(h3n2) strains, respectively, that circulated dur ...201526615216
protection against influenza a virus by vaccination with a recombinant fusion protein linking influenza m2e to human serum albumin (hsa).the highly conserved extracellular domain of m2 protein (m2e) of influenza a viruses has limited immunogenicity on its own. hence, aiming to enhance immunogenicity of m2e protein, optimal approaches remain to be established. in this study, we created recombinant fusion protein vaccines by linking m2e consensus sequence of influenza a viruses with c-terminal domain of human serum albumin (hsa). then hsa/m2e recombinant fusion protein was studied. our results showed that hsa/m2e could induce stron ...201626615805
historical and recent cases of h3 influenza a virus in turkeys in minnesota.subtype h3 influenza a viruses (iavs) are abundant in wild waterfowl and also infect humans, pigs, horses, dogs, and seals. in minnesota, turkeys are important and frequent hosts of iav from wild waterfowl and from pigs. over 48 yr of surveillance history, 11 hemagglutinin (ha) subtypes of iav from waterfowl, as well as two ha subtypes from swine, h1 and h3, have infected turkeys in minnesota. however, there have only been two cases of avian-origin h3 iav infections in turkeys during this 48-yr ...201526629625
[analysis of the neuraminidase amino acid sequences of influenza a/h1n1pdm09, a/h3n2, and b viruses isolated from influenza patients in the 2013/14 japanese influenza season].neuraminidase (na) is an essential surface protein for influenza virus replication. na inhibitors are commonly used for the treatment of influenza patients in japan. several mutations that reduce the effect of na inhibitors have been reported. we sequenced the whole na segment of isolated virus from influenza patients and investigated the relation between the na amino acid sequence and the 50% inhibitory concentration (ic50) of four na inhibitors.201526630841
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
transcription factor runx3 is induced by influenza a virus and double-strand rna and mediates airway epithelial cell apoptosis.influenza a virus (iav) targets airway epithelial cells and exploits the host cell machinery to replicate, causing respiratory illness in annual epidemics and pandemics of variable severity. the high rate of antigenic drift (viral mutation) and the putative antigenic shift (reassortant strains) have raised the need to find the host cell inducible factors modulating iav replication and its pathogenesis to develop more effective antiviral treatment. in this study, we found for the first time that ...201526643317
indole alkaloid glucosides from the roots of isatis indigotica.five new indole alkaloid glucosides named isatindigotindolosides a-e (1-5), along with three known analogs (6-8), were isolated from an aqueous extract of the isatis indigotica roots. their structures including the absolute configurations were determined based on comprehensive spectroscopic data analysis, combined with chemical methods and electronic circular dichroism spectra calculations. in the preliminary assays, compounds 1, 6 and 7 showed antiviral activity against influenza virus a/hanfan ...201626651370
prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know?this review provides for the first time an assessment of the current understanding about the occurrence and the clinical significance of gastrointestinal (gi) symptoms in influenza patients, and their correlation with the presence of human influenza viruses in stools of patients with confirmed influenza virus infection. studies exploring how human influenza viruses spread to the patient's gi tract after a primary respiratory infection have been summarized. we conducted a systematic search of pub ...201526651485
generation and characterization of monoclonal antibodies specific to avian influenza h5n1 hemagglutinin protein.highly pathogenic avian influenza (hpai) h5n1 virus has in the past breached the species barrier from infected domestic poultry to humans in close contact. although human-to-human transmission has previously not been reported, hpai h5n1 virus has pandemic potential owing to gain of function mutation(s) and/or genetic reassortment with human influenza a viruses. monoclonal antibodies (mabs) have been used for diagnosis as well as specific therapeutic candidates in several disease conditions inclu ...201526683184
pentacyclic triterpenes grafted on cd cores to interfere with influenza virus entry: a dramatic multivalent effect.multivalent effect plays an important role in biological processes, particularly in the specific recognition of virus with its host cell during the first step of infection. here we report the synthesis of multivalent pentacyclic triterpene grafted on cyclodextrin core and potency of against influenza entry activity. nine star-shaped compounds containing six, seven and eight pentacyclic triterpene pharmacophore on cyclodextrin scaffold were prepared by way of copper-catalyzed azide-alkyl cycloadd ...201626686050
discovery of influenza a virus neuraminidase inhibitors using support vector machine and naïve bayesian models.neuraminidase (na) is a critical enzyme in the life cycle of influenza virus, which is known as a successful paradigm in the design of anti-influenza agents. however, to date there are no classification models for the virtual screening of na inhibitors. in this work, we built support vector machine and naïve bayesian models of na inhibitors and non-inhibitors, with different ratios of active-to-inactive compounds in the training set and different molecular descriptors. four models with sensitivi ...201626689205
recombinant influenza virus with a pandemic h2n2 polymerase complex has a higher adaptive potential than one with seasonal h2n2 polymerase complex.the reassortment of influenza viral gene segments plays a key role in the genesis of pandemic strains. all of the last three pandemic viruses contained reassorted polymerase complexes with subunits derived from animal viruses, suggesting that the acquisition of a reassorted polymerase complex might have a role in generating these pandemic viruses. here, we studied polymerase activities of the pandemic h2n2, seasonal h2n2 and pandemic h3n2 viruses. we observed that the viral ribonucleoprotein (vr ...201626703222
quercetin as an antiviral agent inhibits influenza a virus (iav) entry.influenza a viruses (iavs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-iav agents. the glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including a/puerto rico/8/34 (h1n1), a/fm-1/47/1 (h1n1), and a/aichi/2/68 (h3n ...201526712783
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
characterization of the localized immune response in the respiratory tract of ferrets following infection with influenza a and b viruses.the burden of infection with seasonal influenza viruses is significant. each year is typically characterized by the dominance of one (sub)type or lineage of influenza a or b virus, respectively. the incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. to improve our understanding of the impacts of seasonal influenza viruses, w ...201526719259
imidazole-based pinanamine derivatives: discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza a virus.we previously reported potent hit compound 4 inhibiting the wild-type influenza a virus a/hk/68 (h3n2) and a/m2-s31n mutant viruses a/ws/33 (h1n1), with its latter activity quite weak. to further increase its potency, a structure-activity relationship study of a series of imidazole-linked pinanamine derivatives was conducted by modifying the imidazole ring of this compound. several compounds of this series inhibited the amantadine-sensitive virus at low micromolar concentrations. among them, 33 ...201626722757
quantifying influenza virus diversity and transmission in humans.influenza a virus is characterized by high genetic diversity. however, most of what is known about influenza evolution has come from consensus sequences sampled at the epidemiological scale that only represent the dominant virus lineage within each infected host. less is known about the extent of within-host virus diversity and what proportion of this diversity is transmitted between individuals. to characterize virus variants that achieve sustainable transmission in new hosts, we examined withi ...201626727660
ring test evaluation of the detection of influenza a virus in swine oral fluids by real-time reverse-transcription polymerase chain reaction and virus isolation.the probability of detecting influenza a virus (iav) in oral fluid (of) specimens was calculated for each of 13 assays based on real-time reverse-transcription polymerase chain reaction (rrt-pcr) and 7 assays based on virus isolation (vi). the of specimens were inoculated with h1n1 or h3n2 iav and serially diluted 10-fold (10(-1) to 10(-8)). eight participating laboratories received 180 randomized of samples (10 replicates × 8 dilutions × 2 iav subtypes plus 20 iav-negative samples) and performe ...201626733728
evolution of 2014/15 h3n2 influenza viruses circulating in us: consequences for vaccine effectiveness and possible new pandemic.a key factor in the effectiveness of the seasonal influenza vaccine is its immunological compatibility with the circulating viruses during the season. here we propose a new bioinformatics approach for analysis of influenza viruses which could be used as an efficient tool for selection of vaccine viruses, assessment of the effectiveness of seasonal influenza vaccines, and prediction of the epidemic/pandemic potential of novel influenza viruses.201526733989
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
deep sequencing reveals potential antigenic variants at low frequencies in influenza a virus-infected humans.influenza vaccines must be frequently reformulated to account for antigenic changes in the viral envelope protein, hemagglutinin (ha). the rapid evolution of influenza virus under immune pressure is likely enhanced by the virus's genetic diversity within a host, although antigenic change has rarely been investigated on the level of individual infected humans. we used deep sequencing to characterize the between- and within-host genetic diversity of influenza viruses in a cohort of patients that i ...201626739054
the pb1 segment of an influenza a virus h1n1 2009pdm isolate enhances the replication efficiency of specific influenza vaccine strains in cell culture and embryonated eggs.influenza vaccine strains (ivss) contain the haemagglutinin (ha) and neuraminidase (na) genome segments of relevant circulating strains in the genetic background of influenza a/pr/8/1934 virus (pr8). previous work has shown that the nature of the pb1 segment may be a limiting factor for the efficient production of ivss. here, we showed that the pb1 segment (pb1gi) from the 2009 pandemic influenza a virus (iav) a/giessen/06/2009 (gi wt, h1n1pdm) may help to resolve (some of) these limitations. we ...201626743314
epidemiology of human coronavirus nl63 infection among hospitalized patients with pneumonia in taiwan.human coronavirus (hcov) nl63 is recognized in association with upper or lower respiratory tract illnesses in children. this study surveyed the prevalence of hcov-nl63 and influenza viruses in patients with influenza-like illness in taiwan during 2010-2011.201526746130
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
prevalence of influenza a virus in exhibition swine during arrival at agricultural fairs.the exhibition swine at agricultural fairs provides a critical human-swine interface that allows for the bidirectional transmission of influenza a virus (iav). previous iav surveillance at the end of fairs has resulted in frequent detection of iav-infected swine; little is known, however, about the frequency with which swine arrive at fairs already infected with iav. we investigated the iav prevalence among exhibition swine entering fairs to better understand the epidemiology of iav in this uniq ...201626750204
are plasma mineral levels related to antibody response to influenza vaccination in older adults?an effective immune response to vaccination may be related to nutritional status. this study examined the association of plasma mineral levels with hemagglutination inhibition (hi) titers produced in response to influenza vaccine in older adults.201626751915
characterization of viral load, viability and persistence of influenza a virus in air and on surfaces of swine production facilities.indirect transmission of influenza a virus (iav) in swine is poorly understood and information is lacking on levels of environmental exposure encountered by swine and people during outbreaks of iav in swine barns. we characterized viral load, viability and persistence of iav in air and on surfaces during outbreaks in swine barns. iav was detected in pigs, air and surfaces from five confirmed outbreaks with 48% (47/98) of oral fluid, 38% (32/84) of pen railing and 43% (35/82) of indoor air sample ...201626757362
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
accelerating influenza research: vaccines, antivirals, immunomodulators and monoclonal antibodies. the manufacture of a new wild-type h3n2 virus for the human viral challenge model.influenza and its associated diseases are a major cause of morbidity and mortality. the united states advisory committee on immunization practices recommends influenza vaccination for everyone over 6 months of age. the failure of the flu vaccine in 2014-2015 demonstrates the need for a model that allows the rapid development of novel antivirals, universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel treatments. to this end we manufactured a new h3n2 influenza ...201626761707
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
influenza in the emergency department: vaccination, diagnosis, and treatment: clinical practice paper approved by american academy of emergency medicine clinical guidelines committee.influenza is an acute respiratory virus that results in significant worldwide morbidity and mortality each year. as emergency physicians, we are often the first to encounter patients with seasonal influenza. it is therefore critical that we draw on the most recent and relevant research when we make clinical decisions regarding the diagnosis, treatment, and prophylaxis of this disease.201626763858
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
discovery of influenza a virus sequence pairs and their combinations for simultaneous heterosubtypic targeting that hedge against antiviral resistance.the multiple circulating human influenza a virus subtypes coupled with the perpetual genomic mutations and segment reassortment events challenge the development of effective therapeutics. the capacity to drug most rnas motivates the investigation on viral rna targets. 123,060 segment sequences from 35,938 strains of the most prevalent subtypes also infecting humans-h1n1, 2009 pandemic h1n1, h3n2, h5n1 and h7n9, were used to identify 1,183 conserved rna target sequences (≥15-mer) in the internal ...201626771381
antiviral action of methylated β-lactoglobulin on the human influenza virus a subtype h3n2.antiviral activity of methylated β-lactoglobulin (met-blg) against h3n2 infected into mdck cell lines depended on concentration of met-blg, viral load, and duration of infection. ic50% of the hemagglutination activity for 1 and 0.2 moi (multiplicity of infection) after 24 h of incubation at 37 °c in the presence of 5% co2 were 20 ± 0.8 and 17 ± 0.7 μg ml(-1) met-blg, respectively. longer incubation period (4 days) was associated with low ic50% of the hemagglutination activity (7.1 ± 0.3 μg ml(-1 ...201026781119
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
design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes.type iii interferons (ifns) (also called ifn-λ: ifn-λ1, ifn-λ2, ifn-λ3, and ifn-λ4) are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type i ifns is weak, and unlike type i ifns that are associated with severe and diverse side effects, type iii ifns cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointes ...201626792983
platform technology to generate broadly cross-reactive antibodies to α-helical epitopes in hemagglutinin proteins from influenza a viruses.we have utilized a de novo designed two-stranded α-helical coiled-coil template to display conserved α-helical epitopes from the stem region of hemagglutinin (ha) glycoproteins of influenza a. the immunogens have all the surface-exposed residues of the native α-helix in the native ha protein of interest displayed on the surface of the two-stranded α-helical coiled-coil template. this template when used as an immunogen elicits polyclonal antibodies which bind to the α-helix in the native protein. ...201626799790
an individualized predictor of health and disease using paired reference and target samples.consider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, called a reference sample. as contrasted to a population averaged reference this reference sample is individualized. automated predictor algorithms that compare and contrast the paired samples to each other could result in a new generation of test panels that ...201626801061
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
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
design, synthesis, and in vitro biological evaluation of novel 6-methyl-7-substituted-7-deaza purine nucleoside analogs as anti-influenza a agents.among many subtypes of influenza a viruses, influenza a(h1n1) and a(h3n2) subtypes are currently circulating among humans (who report 2014-15). therapeutically, the emergence of viral resistance to currently available drugs (adamantanes and neuraminidase inhibitors) has heightened alarms for developing novel drugs that could address diverse targets in the viral replication cycle in order to improve treatment outcomes. to this regard, the design and synthesis of nucleoside analog inhibitors as po ...201626802557
antiviral activity of sa-2 against influenza a virus in vitro/vivo and its inhibition of rna polymerase.a target-free and cell-based approach was applied to evaluate the anti-influenza properties of six newly synthesized benzoic acid derivatives. sa-2, the ethyl 4-(2-hydroxymethyl-5-oxopyrrolidin-1-yl)-3-[3-(3-methylbenzoyl)-thioureido] benzoate (compound 2) was screened as a potential drug candidate. in a cytopathic effect assay, sa-2 dose dependently inhibited h1n1, h3n2 and the oseltamivir-resistant mutant h1n1-h275y influenza viruses in both virus-infected mdck and a549 cells, with 50% effecti ...201626802558
human nasal epithelial cells derived from multiple subjects exhibit differential responses to h3n2 influenza virus infection in vitro. 201626806046
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
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
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
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 characteristics of influenza virus type b lineages circulating in poland.from the time of the hong kong pandemic of 1968-1969, vaccines against influenza are trivalent, containing two subtypes of influenza type a: a/h1n1/ and a/h3n2/, and influenza type b. in 1980, circulation of the new yamagata and victoria lineages of influenza b virus was noted. since both lineages have continued to circulate, the second lineage of influenza b was included into the trivalent vaccine as of the 2013/2014 epidemic season. in poland, co-circulation of influenza type a and b has been ...201626820730
[infectivity titers of each component of the influenza virus in the live vaccine purchased from a parallel import distributing system].currently in japan, the only approved influenza vaccine is the inactivated vaccine which is injected subcutaneously. on the other hand, there is a live vaccine available elsewhere in the world. flumist, an intranasal influenza live vaccine which contains four strains of infectious viruses, has been used in the united states for more than 10 years; the vaccine has been found effective in clinical trials, while it has some limitations such as those on subjects for the administration, strict storag ...201526821520
construction of the influenza a virus transmission tree in a college-based population: co-transmission and interactions between influenza a viruses.co-infection of different influenza a viruses is known to occur but how viruses interact within co-infection remains unknown. an outbreak in a college campus during the 2009 pandemic involved two subtypes of influenza a: persons infected with pandemic a/h1n1; persons infected with seasonal a/h3n2 viruses; and persons infected with both at the same time (co-infection). this provides data to analyse the possible interaction between influenza a viruses within co-infection.201626825326
recombinant influenza virus expressing hiv-1 p24 capsid protein induces mucosal hiv-specific cd8 t-cell responses.influenza viruses are promising mucosal vaccine vectors for hiv but their use has been limited by difficulties in engineering the expression of large amounts of foreign protein. we developed recombinant influenza viruses incorporating the hiv-1 p24 gag capsid into the ns-segment of pr8 (h1n1) and x31 (h3n2) influenza viruses with the use of multiple 2a ribosomal skip sequences. despite the insertion of a sizable hiv-1 gene into the influenza genome, recombinant viruses were readily rescued to hi ...201626826545
[cold-adapted a/krasnodar/101/35/59 (h2n2) strain--a promising strain-donor of attenuation for procuration of live influenza vaccines].study of ts, ca, att phenotype, immunogenicity and protective effectiveness of reassortants obtained by a way of recombination of a new influenza cold-adapted (ca) strain donor of attenuation a/krasnodar/101/35/59 (h2n2) and virulent strain of influenza virus.201626829850
heptapeptide ligands against receptor-binding sites of influenza hemagglutinin toward anti-influenza therapy.the initial attachment of influenza virus to cells is the binding of hemagglutinin (ha) to the sialyloligosaccharide receptor; therefore, the small molecules that inhibit the sugar-protein interaction are promising as ha inhibitors to prevent the infection. we herein demonstrate that sialic acid-mimic heptapeptides are identified through a selection from a primary library against influenza virus ha. in order to obtain lead peptides, an affinity selection from a phage-displayed random heptapeptid ...201626833245
mutations acquired during cell culture isolation may affect antigenic characterisation of influenza a(h3n2) clade 3c.2a viruses.as elsewhere, few (< 15%) sentinel influenza a(h3n2) clade 3c.2a viruses that dominated in canada during the 2014/15 season could be antigenically characterised by haemagglutination inhibition (hi) assay. clade 3c.2a viruses that could be hi-characterised had acquired genetic mutations during in vitro cell culture isolation that modified the potential glycosylation motif found in original patient specimens and the consensus sequence of circulating viruses at amino acid positions 158-160 of the h ...201626836031
predicting the mutating distribution at antigenic sites of the influenza virus.mutations of the influenza virus lead to antigenic changes that cause recurrent epidemics and vaccine resistance. preventive measures would benefit greatly from the ability to predict the potential distribution of new antigenic sites in future strains. by leveraging the extensive historical records of ha sequences for 90 years, we designed a computational model to simulate the dynamic evolution of antigenic sites in a/h1n1. with templates of antigenic sequences, the model can effectively predict ...201626837263
a natural component from euphorbia humifusa willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein.the need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. we identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-o-galloyl-β-d-glucopyranoside (tgbg) from euphorbia humifusa willd showed broad-spectrum anti-influenza activity ...201626850850
directed selection of influenza virus produces antigenic variants that match circulating human virus isolates and escape from vaccine-mediated immune protection.influenza vaccination does not provide 100% protection from infection, partly due to antigenic drift of the haemagglutinin (ha) protein. low serum antibody titres increase the risk of infection. to determine whether there were additional correlates of risk, we examined the relationship between human serum immunity and antigenic variation in seasonal h3n2 influenza viruses. seasonal h3n2 vaccine strains grown in the presence of heterogeneous human or mono-specific ferret antisera selected variant ...201626854888
effectiveness of subunit influenza vaccination in the 2014-2015 season and residual effect of split vaccination in previous seasons.in navarra, spain, subunit vaccine was first used in the 2014-2015 season, whereas trivalent split-virion influenza vaccines had been used in previous seasons. we estimate the effectiveness of the subunit vaccine in the current season and split vaccine in the two previous seasons against laboratory-confirmed influenza in the 2014-2015 season.201626854911
long-term shedding of influenza virus, parainfluenza virus, respiratory syncytial virus and nosocomial epidemiology in patients with hematological disorders.respiratory viruses are a cause of upper respiratory tract infections (urti), but can be associated with severe lower respiratory tract infections (lrti) in immunocompromised patients. the objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (rsv) and the duration of viral shedding in hematological patients. nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and rsv on a ...201626866481
airborne influenza a is detected in the personal breathing zone of swine veterinarians.the 2009 h1n1 pandemic emphasized a need to evaluate zoonotic transmission of influenza a in swine production. airborne influenza a virus has been detected in swine facilities during an outbreak. however, the personal exposure of veterinarians treating infected swine has not been characterized. two personal bioaerosol samplers, the niosh bioaerosol sampler and the personal high-flow inhalable sampler head (phish), were placed in the breathing zone of veterinarians treating swine infected with ei ...201626867129
comparison of as03 and alum on immune responses elicited by a/h3n2 split influenza vaccine in young, mature and aged balb/c mice.there is great interest in developing more effective influenza vaccines for the elderly. oil-in-water adjuvants can boost humoral responses to seasonal vaccines in elderly subjects but relatively little is known about their mechanism of action.201626873056
conserved stem fragment from h3 influenza hemagglutinin elicits cross-clade neutralizing antibodies through stalk-targeted blocking of conformational change during membrane fusion.currently available influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies due to the mutability of virus sequences and conformational changes during protective immunity, thereby limiting their efficacy. this problem needs to be addressed by further understanding the mechanisms of neutralization and finding the desired neutralizing site during membrane fusion. this study specifically focused on viruses of the h3n2 subtype, which have persisted as a principal source of ...201626875772
new england harbor seal h3n8 influenza virus retains avian-like receptor specificity.an influenza h3n8 virus, carrying mammalian adaptation mutations, was isolated from new england harbor seals in 2011. we sought to assess the risk of its human transmissibility using two complementary approaches. first, we tested the binding of recombinant hemagglutinin (ha) proteins of seal h3n8 and human-adapted h3n2 viruses to respiratory tissues of humans and ferrets. for human tissues, we observed strong tendency of the seal h3 to bind to lung alveoli, which was in direct contrast to the hu ...201626888262
the proteolytic activation of (h3n2) influenza a virus hemagglutinin is facilitated by different type ii transmembrane serine proteases.cleavage of influenza virus hemagglutinin (ha) by host cell proteases is necessary for viral activation and infectivity. in humans and mice, members of the type ii transmembrane protease family (ttsp), e.g., tmprss2, tmprss4, and tmprss11d (hat), have been shown to cleave influenza virus ha for viral activation and infectivity in vitro recently, we reported that inactivation of a single ha-activating protease gene,tmprss2, in knockout mice inhibits the spread of h1n1 influenza viruses. however, ...201626889029
update: influenza activity--united states, october 4, 2015-february 6, 2016.from october through mid-december 2015, influenza activity remained low in most regions of the united states. activity began to increase in late december 2015 and continued to increase slowly through early february 2016. influenza a viruses have been most frequently identified, with influenza a (h3n2) viruses predominating during october until early december, and influenza a (h1n1)pdm09 viruses predominating from mid-december until early february. most of the influenza viruses characterized duri ...201626891596
influenza b vaccine lineage selection--an optimized trivalent vaccine.epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. the influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza a/h3n2, a/h1n1, and influ ...201626896685
a novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses.a safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. in light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, p9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza a virus h1n1, h3n2, h5n1, h7n7, h7n9, sars-cov and mers-cov. the antiviral activity of p9 w ...201626911565
role of n terminus-truncated ns1 proteins of influenza a virus in inhibiting irf3 activation.the ns1 protein encoded by influenza a virus antagonizes the interferon response through various mechanisms, including blocking cellular mrna maturation by binding the cellular cpsf30 3' end processing factor and/or suppressing the activation of interferon regulatory factor 3 (irf3). in the present study, we identified two truncated ns1 proteins that are translated from internal augs at positions 235 and 241 of the ns1 open reading frame. we analyzed the cellular localization and function of the ...201626912617
neuraminidase activity and resistance of 2009 pandemic h1n1 influenza virus to antiviral activity in bronchoalveolar fluid.human bronchoalveolar fluid is known to have anti-influenza activity. it is believed to be a frontline innate defense against the virus. several antiviral factors, including surfactant protein d, are believed to contribute to the activity. the 2009 pandemic h1n1 influenza virus was previously shown to be less sensitive to surfactant protein d. nevertheless, whether different influenza virus strains have different sensitivities to the overall anti-influenza activity of human bronchoalveolar fluid ...201626912622
influenza h3n2 infection of the collaborative cross founder strains reveals highly divergent host responses and identifies a unique phenotype in cast/eij mice.influenza a virus is a zoonotic pathogen that poses a major threat to human and animal health. the severe course of influenza infection is not only influenced by viral virulence factors but also by individual differences in the host response. to determine the extent to which the genetic background can modulate severity of an infection, we studied the host responses to influenza infections in the eight genetically highly diverse collaborative cross (cc) founder mouse strains.201626921172
safety, immunogenicity and cross-reactivity of a northern hemisphere 2013-2014 seasonal trivalent inactivated split influenza virus vaccine, anflu®.anflu® is a seasonal trivalent inactivated split-virion influenza vaccine manufactured by sinovac biotech co., ltd. the objectives of this study were to evaluate the safety of anflu® (2013-14 formulation: h1n1, h3n2 and byam) in infants and adults and its immunogenicity and cross-reactivity against mismatched influenza b lineage and avian influenza a(h7n9) viruses (hereafter bvic and h7n9, respectively) in adults. in this phase iv open label trial, infants 6-35 months old (n=61) each received tw ...201626934750
virological surveillance of influenza and other respiratory viruses during six consecutive seasons from 2006 to 2012 in catalonia, spain.most attention is given to seasonal influenza and respiratory syncytial virus outbreaks, but the cumulative burden caused by other respiratory viruses (rv) is not widely considered. the aim of the present study is to describe the circulation of rv in the general population during six consecutive seasons from 2006 to 2012 in catalonia, spain. cell culture, immunofluorescence and pcr-based assays were used for the rv laboratory-confirmation and influenza subtyping. phylogenetic and molecular chara ...201626939538
comparison between mdck and mdck-siat1 cell lines as preferred host for cell culture-based influenza vaccine production.to evaluate mdck and mdck-siat1 cell lines for their ability to produce the yield of influenza virus in different multiplicities of infection.201626945752
serological survey for emerging canine h3n8 and h3n2 influenza viruses in pet and village dogs in nigeria.in nigeria, keeping of dogs as pets and guards is gaining popularity. to determine whether infection of dogs with novel canine influenza virus (civ) of equine (h3n8) and avian (h3n2) origins had occurred in nigeria, we screened pet and village dogs from lagos, ibadan, odeda and sagamu in southwestern nigeria for antibodies to civ h3n8 and h3n2.201426949788
vaccination with 2014-15 seasonal inactivated influenza vaccine elicits cross-reactive anti-ha antibodies with strong adcc against antigenically drifted circulating h3n2 virus in humans.it is well established that virus neutralizing (vn) antibodies to hemagglutinin (ha) antigens of influenza a viruses provide optimal protection against antigenically matched strains of influenza a viruses. in contrast, little is known about the potential role of ha-specific, non-neutralizing antibodies in protection against human influenza illness at present. in this study, we show that individuals vaccinated with the 2014-15 seasonal inactivated influenza vaccine displayed strong a/h3n2 ha-spec ...201626950058
high conservation level of cd8(+) t cell immunogenic regions within an unusual h1n2 human influenza variant.current seasonal influenza vaccines require regular updates due to antigenic drift causing loss of effectiveness and therefore providing little or no protection against novel influenza a subtypes. next generation vaccines capable of eliciting cd8(+) t cell (ctl) mediated cross-protective immunity may offer a long-term alternative strategy. however, measuring pre- and existing levels of ctl cross-protection in humans is confounded by differences in infection histories across individuals. during 2 ...201626950895
[determination of influenza virus h5n1 and h7n9 using masa technology].to set up a new rapid method for the rapid determination of influenza virus h5n1 and h7n9 basing on the multi-analyte suspension array (masa) technology. sequence analysis and design of degenerate primers and specific probes were set in the comparison and analysis of h5, n1, h7 and n9 genes. in combination with masa technology, these primers and probes were used for the determination of samples of h5n1 and h7n9 and other subtypes ( h1n1, ph1n1, h5n2, h3n2 and h9n2). we developed a rapid determin ...201526951004
prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses.human seasonal influenza viruses evolve rapidly, enabling the virus population to evade immunity and reinfect previously infected individuals. antigenic properties are largely determined by the surface glycoprotein hemagglutinin (ha), and amino acid substitutions at exposed epitope sites in ha mediate loss of recognition by antibodies. here, we show that antigenic differences measured through serological assay data are well described by a sum of antigenic changes along the path connecting viruse ...201626951657
induction of systemic and mucosal immunity and maintenance of its memory against influenza a virus by nasal vaccination using a new mucosal adjuvant sf-10 derived from pulmonary surfactant in young cynomolgus monkeys.induction of systemic and mucosal immunity and maintenance of its memory was investigated in 12 young male cynomolgus monkeys after intranasal instillation of flu vaccine using a new mucosal adjuvant sf-10 derived from pulmonary surfactant constituents. split-product of influenza virus a/california/7/2009(h1n1)pdm hemagglutinin vaccine (hav) at 15 μg with or without sf-10 and the adjuvant alone were instilled intranasally three times every 2 weeks. sf-10-adjuvanted hav (sf-10-hav) elicited signi ...201626954466
a novel small-molecule inhibitor of influenza a virus acts by suppressing pa endonuclease activity of the viral polymerase.the rna-dependent rna polymerase of influenza a virus comprises conserved and independently-folded subdomains with defined functionalities. the n-terminal domain of the pa subunit (pa(n)) harbors the endonuclease function so that it can serve as a desired target for drug discovery. to identify a class of anti-influenza inhibitors that impedes pa(n) endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitory assay with the d ...201626956222
antigenic drift of a/h3n2/virus and circulation of influenza-like viruses during the 2014/2015 influenza season in poland.morbidity rates of influenza could be greatly reduced due to vaccination. however, the virus is able to evolve through genetic mutations, which is why vaccines with updated composition are necessary every season. their effectiveness depends on whether there is a good antigenic match between circulating viruses and vaccine strains. in poland, the 2014/2015 influenza epidemic started in week 5 (january/february) of 2015 and continued until week 17 (april) of 2015. the influenza activity was modera ...201626956457
influenza vaccine manufacturing: effect of inactivation, splitting and site of manufacturing. comparison of influenza vaccine production processes.the aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. four split and two whole inactivated virus (wiv) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. one clarified harvest of influenza h3n2 a/uruguay virus prepared on 25.000 fertilized eggs was divided equa ...201626959983
effects of egg-adaptation on receptor-binding and antigenic properties of recent influenza a (h3n2) vaccine viruses.influenza a virus (subtype h3n2) causes seasonal human influenza and is included as a component of influenza vaccines. the majority of vaccine viruses are isolated and propagated in eggs, which commonly results in amino acid substitutions in the haemagglutinin (ha) glycoprotein. these substitutions can affect virus receptor-binding and alter virus antigenicity, thereby, obfuscating the choice of egg-propagated viruses for development into candidate vaccine viruses. to evaluate the effects of egg ...201626974849
detailed report on 2014/15 influenza virus characteristics, and estimates on influenza virus vaccine effectiveness from austria's sentinel physician surveillance network.influenza vaccine effectiveness (ve) is influenced by the antigenic similarity between vaccine- and circulating strains.201626975056
cooperation between distinct viral variants promotes growth of h3n2 influenza in cell culture.rna viruses rapidly diversify into quasispecies of related genotypes. this genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. here, we demonstrate strong cooperation between two h3n2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. residue 151 is often annotated as an ambiguous amino acid i ...201626978794
molecular characterization of a novel reassortant h1n2 influenza virus containing genes from the 2009 pandemic human h1n1 virus in swine from eastern china.pandemic outbreaks of h1n1 swine influenza virus have been reported since 2009. reassortant h1n2 viruses that contain genes from the pandemic h1n1 virus have been isolated in italy and the united states. however, there is limited information regarding the molecular characteristics of reassortant h1n2 swine influenza viruses in eastern china. active influenza surveillance programs in zhejiang province identified a novel h1n2 influenza virus isolated from pigs displaying clinical signs of influenz ...201626980674
viral infections in children in the 2014/2015 epidemic season in poland.in every epidemic season, viral infections affect the general population, including children, which is an underestimated issue. the present study demonstrates the results of examination of 802 clinical samples obtained from pediatric patients aged 0-14 years during the 2014/2015 epidemic season in poland. the study was part of the virological surveillance systems - sentinel and non-sentinel. a positive result for virological infection was obtained in 50.9 % of samples tested. the distribution of ...201626987329
a plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and t cell response in healthy adults.recent issues regarding efficacy of influenza vaccines have re-emphasized the need of new approaches to face this major public health issue. in a phase 1-2 clinical trial, healthy adults received one intramuscular dose of a seasonal influenza plant-based quadrivalent virus-like particle (qvlp) vaccine or placebo. the hemagglutination inhibition (hi) titers met all the european licensure criteria for the type a influenza strains at the 3μg/strain dose and for all four strains at the higher dosage ...201626987887
characterization of a novel h3n2 influenza virus isolated from domestic ducks in china.cases of human infection with a novel h7n9 avian influenza virus (aiv) were first reported in march 2013, which caused 115 deaths within a single year. beyond that, other subtypes of h7 aiv were isolated from poultry in eastern china during the same period, including h7n7 and h7n2 aiv. in the present study, a subtype h3n2 aiv was isolated from ducks from anhui province, china. sequence and phylogenetic analyses revealed that seven gene segments of this virus showed the highest sequence homology ...201627000112
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