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early estimates of seasonal influenza vaccine effectiveness - united states, january 2015.in the united states, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months. each season since 2004-05, cdc has estimated the effectiveness of seasonal influenza vaccine in preventing medically attended acute respiratory illness (ari) associated with laboratory-confirmed influenza. this season, early estimates of influenza vaccine effectiveness are possible because of widespread, early circulation of influenza viruses. by january 3, 2015, 46 states were expe ...201525590680
effective lethal mutagenesis of influenza virus by three nucleoside analogs.lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many rna viruses. this approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. we investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. all three drugs were acti ...201525589650
detection of a transient r292k mutation in influenza a/h3n2 viruses shed for several weeks by an immunocompromised patient.we describe the case of an immunocompromised patient, positive for influenza a virus (h3n2), in whom the neuraminidase r292k mutation was transiently detected during oseltamivir treatment. the r292k mutation was identified by direct testing in 3 of 11 respiratory specimens collected throughout the patient's illness but in none of the cultures from those specimens.201525588658
serological evidence of avian influenza virus and canine influenza virus infections among stray cats in live poultry markets, china.from january 2010 to january 2012, we collected sera samples from 700 stray cats living in close proximity to poultry farms or poultry markets in 4 provinces in china. a number of cats had evidence of avian and canine influenza virus infection: avian h9n2 [24 by hi ≥1:20 and 16 by microneutralization (mn) assay ≥1:80]; avian h5n1 (9 by hi ≥1:20 and 3 by mn assay ≥1:80) and canine h3n2 (32 by hi ≥1:20 and 18 by mn ≥1:80). bivariate analyses revealed that cats sampled near live poultry markets and ...201525575880
integrated centrifugal reverse transcriptase loop-mediated isothermal amplification microdevice for influenza a virus detection.an integrated reverse transcriptase loop-mediated isothermal amplification (rt-lamp) microdevice which consists of microbead-assisted rna purification and rt-lamp with real-time monitoring by a miniaturized optical detector was demonstrated. the integrated rt-lamp microdevice includes four reservoirs for a viral rna sample (purified influenza a viral rna or lysates), a washing solution (70% ethanol), an elution solution (rnase-free water), and an rt-lamp cocktail, and two chambers (a waste chamb ...201525569879
comparison of multiplex rt-pcr with virus isolation for detection, typing and sub-typing of influenza virus from influenza-like illness cases.influenza epidemics and periodic pandemics occur worldwide resulting in significant mortality, morbidity and economic loss. there is need for a sensitive, rapid and cost-effective assay to detect, type and sub-type influenza viruses, as cell culture has a long turnaround time.201525560005
detection of influenza antigenic variants directly from clinical samples using polyclonal antibody based proximity ligation assays.identification of antigenic variants is the key to a successful influenza vaccination program. the empirical serological methods to determine influenza antigenic properties require viral propagation. here a novel quantitative pcr-based antigenic characterization method using polyclonal antibody and proximity ligation assays, or so-called polypla, was developed and validated. this method can detect a viral titer that is less than 1000 tcid50/ml. not only can this method differentiate between diff ...201525546251
european surveillance network for influenza in pigs: surveillance programs, diagnostic tools and swine influenza virus subtypes identified in 14 european countries from 2010 to 2013.swine influenza causes concern for global veterinary and public health officials. in continuing two previous networks that initiated the surveillance of swine influenza viruses (sivs) circulating in european pigs between 2001 and 2008, a third european surveillance network for influenza in pigs (esnip3, 2010-2013) aimed to expand widely the knowledge of the epidemiology of european sivs. esnip3 stimulated programs of harmonized siv surveillance in european countries and supported the coordinatio ...201425542013
pathogenicity and transmissibility of novel reassortant h3n2 influenza viruses with 2009 pandemic h1n1 genes in pigs.at least 10 different genotypes of novel reassortant h3n2 influenza viruses with 2009 pandemic h1n1 [a(h1n1)pdm09] gene(s) have been identified in u.s. pigs, including the h3n2 variant with a single a(h1n1)pdm09 m gene, which has infected more than 300 people. to date, only three genotypes of these viruses have been evaluated in animal models, and the pathogenicity and transmissibility of the other seven genotype viruses remain unknown. here, we show that three h3n2 reassortant viruses that cont ...201525540372
safety and immunogenicity of cell culture-derived a/h3n2 variant influenza vaccines: a phase i randomized, observer-blind, dose-ranging study.a/h3n2 variant (h3n2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important.201525538277
cross-reactive immunity against influenza viruses in children and adults following 2009 pandemic h1n1 infection.2009 h1n1 pandemic influenza (a(h1n1)pdm09) virus infected large numbers of people worldwide. recent studies suggest infection with a(h1n1)pdm09 virus elicited cross-reactive anti-hemagglutinin (ha) memory b cell response to conserved regions of ha. however, the breadth and magnitude of cross-reactive immunity in children and adults following a(h1n1)pdm09 infection are unknown.201525513756
[ability of the influenza viruses and their envelope proteins to stimulates endothelial cells apoptosis in vitro].the ability of the modern epidemic strains of influenza virus type a (subtypes h5n1, h3n2, h1n1pdm) and their surface proteins, hemagglutinin (ha) and neuraminidase to cause the activation of the cellular protein caspase-3 and stimulate the emergence of phosphatidylserine on the membrane of human endothelial cell line eahy926 has been studied. it was questioned how the viruses and their surface proteins that were studied cause the activation of caspase-3 after 0.5 h of exposure that recorded imm ...201325509110
chimeric neuraminidase and mutant pb1 gene constellation improves growth and yield of h5n1 vaccine candidate virus.we previously showed that a mutated pb1 gene improved the growth kinetics of a h3n2 influenza reassortant. here, we showed that the same mutations improved the growth kinetics of a virus containing the a/vietnam/1203/2004 (h5n1) haemagglutinin and neuraminidase (na). total protein yield and na activity were increased when a chimeric na was included. these increases indicated that the synergistic effect was due to the gene constellation containing both the altered pb1 gene and the chimeric na gen ...201525502649
episodic nucleotide substitutions in seasonal influenza virus h3n2 can be explained by stochastic genealogical process without positive selection.nucleotide substitutions in the ha1 domain of seasonal influenza virus h3n2 occur in temporal clusters, which was interpreted as a result of recurrent selective sweeps underlying antigenic drift. however, classical theory by watterson suggests that episodic substitutions are mainly due to stochastic genealogy combined with unique genetic structure of influenza virus: high mutation rate over a nonrecombining viral segment. this explains why even larger variance in the number of allelic fixations ...201525492497
influenza vaccine effectiveness assessment through sentinel virological data in three post-pandemic seasons.influenza vaccination aims at reducing the incidence of serious disease, complications and death among those with the most risk of severe influenza disease. influenza vaccine effectiveness (ve) through sentinel surveillance data from the pidirac program (daily acute respiratory infection surveillance of catalonia) during 2010-2011, 2011-2012, and 2012-2013 influenza seasons, with three different predominant circulating influenza virus (iv) types [a(h1n1)pdm09, a(h3n2) and b, respectively] was as ...201525483540
ten years (2004-2014) of influenza surveillance in northern italy.as the regional influenza reference centre operating within the italian network influnet, here we report data on virological and epidemiological surveillance of influenza, as well as on the vaccination coverage rates achieved in lombardy (northern italy) over 10 consecutive winter seasons (2004-2014).   over the past 10 years, influenza vaccine coverage declined both in the general population (from 15.7% in 2004-2005 to 11.7% in 2013-2014) and in the vaccine-target population of individuals ≥65- ...201525483536
computational insights into the inhibition of influenza viruses by rupestonic acid derivatives: pharmacophore modeling, 3d-qsar, comfa and comsia studies.the pharmacophore modeling and 3d-qsar studies were performed on a series of amino alkyl rupestonates (rupestonic acid) derivatives reported for h1n1, h3n2 and influenza b virus, na inhibition. in order to improve the efficacy of amino alkyl rupestonates derivatives, a four point pharmacophore model with one acceptor and three hydrophobic regions was developed. furthermore, the 3d-qsar model was generated based on the pharmacophore hypothesis (ahhh) for each subtype. the hypothesis was more sign ...201525483013
flipping in the pore: discovery of dual inhibitors that bind in different orientations to the wild-type versus the amantadine-resistant s31n mutant of the influenza a virus m2 proton channel.influenza virus infections lead to numerous deaths and millions of hospitalizations each year. one challenge facing anti-influenza drug development is the heterogeneity of the circulating influenza viruses, which comprise several strains with variable susceptibility to antiviral drugs. for example, the wild-type (wt) influenza a viruses, such as the seasonal h1n1, tend to be sensitive to antiviral drugs, amantadine and rimantadine, while the s31n mutant viruses, such as the pandemic 2009 h1n1 (h ...201425470189
novel triple reassortant h1n2 influenza viruses bearing six internal genes of the pandemic 2009/h1n1 influenza virus were detected in pigs in china.the pandemic a/h1n1 influenza viruses emerged in both mexico and the united states in march 2009, and were transmitted efficiently in the human population. transmissions of the pandemic 2009/h1n1 virus from humans to poultry and other species of mammals were reported from several continents during the course of the 2009 h1n1 pandemic. reassortant h1n1, h1n2, and h3n2 viruses containing genes of the pandemic 2009/h1n1 viruses appeared in pigs in some countries.201425467861
combination of multiplex reverse-transcription loop-mediated isothermal amplification with an immunochromatographic strip for subtyping influenza a virus.considering the fatal human victims and economic loss by the annual epidemic influenza virus, the development of a rapid and convenient genetic analysis methodology is demanding for timely on-site pathogen detection. in this study, we utilized reverse-transcription loop-mediated isothermal amplification (rt-lamp) for multiplex target gene amplification, and the resultant amplicons were analyzed on the immunochromatographic strip (ics) for subtyping influenza a virus. through the optimized primer ...201525467501
efficient replication and strong induction of innate immune responses by h9n2 avian influenza virus in human dendritic cells.avian influenza a (h9n2) viruses have occasionally been identified in humans with upper respiratory tract infections. the novel h7n9/2013 virus identified in china shows that a low pathogenic avian influenza (lpai) virus can be highly pathogenic in humans. therefore, it is important to understand virus-host cell interactions and immune responses triggered by lpai viruses in humans. we found that lpai a/hong kong/1073/99 (h9n2) virus replicated efficiently in human dendritic cells (dcs). the h9n2 ...201425461529
drug susceptibility of influenza a/h3n2 strains co-circulating during 2009 influenza pandemic: first report from mumbai.from its first instance in 1977, resistance to amantadine, a matrix (m2) inhibitor has been increasing among influenza a/h3n2, thus propelling the use of oseltamivir, a neuraminidase (na) inhibitor as a next line drug. information on drug susceptibility to amantadine and neuraminidase inhibitors for influenza a/h3n2 viruses in india is limited with no published data from mumbai. this study aimed at examining the sensitivity to m2 and na inhibitors of influenza a/h3n2 strains isolated from 2009 t ...201525461259
synergistic effect of nitazoxanide with neuraminidase inhibitors against influenza a viruses in vitro.the emergence of drug-resistant influenza a virus (iav) strains represents a serious threat to global human health and underscores the need for novel approaches to anti-influenza chemotherapy. combination therapy with drugs affecting different iav targets represents an attractive option for influenza treatment. we have previously shown that the thiazolide anti-infective nitazoxanide (ntz) inhibits h1n1 iav replication by selectively blocking viral hemagglutinin maturation. herein we investigate ...201525451059
a vero-cell-adapted vaccine donor strain of influenza a virus generated by serial passages.a cell culture-based vaccine production system is preferred for the large-scale production of influenza vaccines and has advantages for generating vaccines against highly pathogenic influenza a viruses. vero cells have been widely used in human vaccine manufacturing, and the safety of these cells has been well demonstrated. however, the most commonly used influenza-vaccine donor virus, a/puerto rico/8/1934 (pr8) virus, does not grow efficiently in vero cells. therefore, we adapted the pr8 virus ...201525448099
progressive antigenic drift and phylogeny of human influenza a(h3n2) virus over five consecutive seasons (2009-2013) in hangzhou, china.vaccine efficacy (ve) can be affected by progressive antigenic drift or any new reassortment of influenza viruses. to effectively track the evolution of human influenza a(h3n2) virus circulating in hangzhou, china, a total of 65 clinical specimens were selected randomly from outpatients infected by a(h3n2) viruses during the study period from november 2009 to december 2013. the results of reduced ve and antigenic drift of the correspondent epitopes (c-d-e to a-b) suggest that the current vaccine ...201425447724
baicalin inhibits autophagy induced by influenza a virus h3n2.baicalin, a natural product isolated from scutellariaradix, has been reported to have significant in vivo and in vitro anti-influenza virus activity, but the underlying mechanism remains poorly understood. in this study, we found that baicalin inhibited autophagy induced by influenza virus a3/beijing/30/95 (h3n2) in both a549 and ana-1 cells. the results showed that h3n2 induced autophagy by suppressing mtor signaling pathway, which however could be significantly inhibited by baicalin. baicalin ...201525446340
continued effectiveness of laninamivir octanate hydrate for influenza treatment in japan: comparison between the 2011-2012 and 2012-2013 influenza seasons.the clinical effectiveness of laninamivir octanoate hydrate (laninamivir) was investigated in the japanese 2012-2013 influenza season for comparison with that of the japanese 2011-2012 influenza season. a total of 235 patients were enrolled, of whom 210 were evaluated for the duration of fever and other symptoms. the median durations of fever for a(h3n2) were 32.0 and 38.0 h and the median durations of symptoms for the a(h3n2) were 102.0 and 84.0 h for patients aged under 10 and 10 years or olde ...201425444677
poly i:c adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs.swine influenza is widely prevalent in swine herds in north america and europe causing enormous economic losses and a public health threat. pigs can be infected by both avian and mammalian influenza viruses and are sources of generation of reassortant influenza viruses capable of causing pandemics in humans. current commercial vaccines provide satisfactory immunity against homologous viruses; however, protection against heterologous viruses is not adequate. in this study, we evaluated the protec ...201525437101
influenza pneumonia surveillance among hospitalized adults may underestimate the burden of severe influenza disease.studies seeking to estimate the burden of influenza among hospitalized adults often use case definitions that require presence of pneumonia. the goal of this study was to assess the extent to which restricting influenza testing to adults hospitalized with pneumonia could underestimate the total burden of hospitalized influenza disease.201425423025
molecular characterization of h3n2 influenza a viruses isolated from ontario swine in 2011 and 2012.data about molecular diversity of commonly circulating type a influenza viruses in ontario swine are scarce. yet, this information is essential for surveillance of animal and public health, vaccine updates, and for understanding virus evolution and its large-scale spread.201425416300
antibody landscapes after influenza virus infection or vaccination.we introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. we generated antibody landscapes to study immune profiles covering 43 years of influenza a/h3n2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. upon infection and vaccination, titers increased broadly, including ...201425414313
the k526r substitution in viral protein pb2 enhances the effects of e627k on influenza virus replication.host-adaptive strategies, such as the e627k substitution in the pb2 protein, are critical for replication of avian influenza a viruses in mammalian hosts. here we show that mutation pb2-k526r is present in some human h7n9 influenza isolates, in nearly 80% of h5n1 human isolates from indonesia and, in conjunction with e627k, in almost all seasonal h3n2 viruses since 1970. polymerase complexes containing pb2-526r derived from h7n9, h5n1 or h3n2 viruses exhibit increased polymerase activity. pb2-52 ...201425409547
influenza vaccine effectiveness in the united states during 2012-2013: variable protection by age and virus type.during the 2012-2013 influenza season, there was cocirculation of influenza a(h3n2) and 2 influenza b lineage viruses in the united states.201525406334
field study on swine influenza virus (siv) infection in weaner pigs and sows.the aim of this field study was to explore the occurrence of and factors associated with the detection of swine influenza virus (siv) by rtqpcr in weaner pigs and sows from herds with a history of respiratory or reproductive disorders.201425405955
comparative mutational analyses of influenza a viruses.the error-prone rna-dependent rna polymerase (rdrp) and external selective pressures are the driving forces for rna viral diversity. when confounded by selective pressures, it is difficult to assess if influenza a viruses (iav) that have a wide host range possess comparable or distinct spontaneous mutational frequency in their rdrps. we used in-depth bioinformatics analyses to assess the spontaneous mutational frequencies of two rdrps derived from human seasonal (a/wuhan/359/95; wuhan) and h5n1 ...201525404565
substrate specificity of avian influenza h5n1 neuraminidase.to characterise neuraminidase (na) substrate specificity of avian influenza h5n1 strains from humans and birds comparing to seasonal influenza virus.201425396120
predicting evolution from the shape of genealogical trees.given a sample of genome sequences from an asexual population, can one predict its evolutionary future? here we demonstrate that the branching patterns of reconstructed genealogical trees contains information about the relative fitness of the sampled sequences and that this information can be used to predict successful strains. our approach is based on the assumption that evolution proceeds by accumulation of small effect mutations, does not require species specific input and can be applied to a ...201425385532
non-avian animal reservoirs present a source of influenza a pb1-f2 proteins with novel virulence-enhancing markers.pb1-f2 protein, expressed from an alternative reading frame of most influenza a virus (iav) pb1 segments, may possess specific residues associated with enhanced inflammation (l62, r75, r79, and l82) and cytotoxicity (i68, l69, and v70). these residues were shown to increase the pathogenicity of primary viral and secondary bacterial infections in a mouse model. in contrast to human seasonal influenza strains, virulence-associated residues are present in pb1-f2 proteins from pandemic h1n1 1918, h2 ...201425368997
multiplex rt-pcr and indirect immunofluorescence assays for detection and subtyping of human influenza virus in tunisia.influenza viruses are negative stranded segmented rna viruses belonging to orthomyxoviridae family. they are classified into three types a, b, and c. type a influenza viruses are classified into subtypes according to the antigenic characters of the surface glycoproteins: hemagglutinin (h) and neuraminidase (n). the aim of the present study is to develop a fast and reliable multiplex rt-pcr technique for detecting simultaneously the subtypes a/h1n1 and a/h3n2 of influenza virus. our study include ...201525366277
detection of novel reassortant influenza a (h3n2) and h1n1 2009 pandemic viruses in swine in hanoi, vietnam.from may to september 2013, monthly samples were collected from swine in a vietnamese slaughterhouse for influenza virus isolation and serological testing. a(h1n1)pdm09 viruses and a novel h3n2 originating from reassortment between a(h1n1)pdm09 and novel viruses of the north american triple reassortant lineage were isolated. serological results showed low seroprevalence for the novel h3n2 virus and higher seroprevalence for a(h1n1)pdm09 viruses. in addition, serology suggested that other swine i ...201525363845
antigenic and genomic characterization of human influenza a and b viruses circulating in argentina after the introduction of influenza a(h1n1)pdm09.this study was conducted as part of the argentinean influenza and other respiratory viruses surveillance network, in the context of the global influenza surveillance carried out by the world health organization (who). the objective was to study the activity and the antigenic and genomic characteristics of circulating viruses for three consecutive seasons (2010, 2011 and 2012) in order to investigate the emergence of influenza viral variants. during the study period, influenza virus circulation w ...201425351708
safety and immunogenicity of a novel cold-adapted modified-live equine influenza virus vaccine.to design and evaluate the safety and immunogenicity of a modified-live vaccine to prevent equine influenza virus (eiv) infection based on the novel reassortant cold-adapted strain a/hk/otar/6:2/2010.201425348146
respiratory viruses and bacteria among pilgrims during the 2013 hajj.pilgrims returning from the hajj might contribute to international spreading of respiratory pathogens. nasal and throat swab specimens were obtained from 129 pilgrims in 2013 before they departed from france and before they left saudi arabia, and tested by pcr for respiratory viruses and bacteria. overall, 21.5% and 38.8% of pre-hajj and post-hajj specimens, respectively, were positive for ≥1 virus (p = 0.003). one third (29.8%) of the participants acquired ≥1 virus, particularly rhinovirus (14. ...201425341199
epidemiological and virological characteristics of influenza viruses circulating in cambodia from 2009 to 2011.the cambodian national influenza center (nic) monitored and characterized circulating influenza strains from 2009 to 2011.201425340711
[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
polymerase discordance in novel swine influenza h3n2v constellations is tolerated in swine but not human respiratory epithelial cells.swine-origin h3n2v, a variant of h3n2 influenza virus, is a concern for novel reassortment with circulating pandemic h1n1 influenza virus (h1n1pdm09) in swine because this can lead to the emergence of a novel pandemic virus. in this study, the reassortment prevalence of h3n2v with h1n1pdm09 was determined in swine cells. reassortants evaluated showed that the h1n1pdm09 polymerase (pa) segment occurred within swine h3n2 with ∼ 80% frequency. the swine h3n2-human h1n1pdm09 pa reassortant (swh3n2-h ...201425330303
variations in ph sensitivity, acid stability, and fusogenicity of three influenza virus h3 subtypes.influenza a virus strains adapt to achieve successful entry into host species. entry is mediated by the viral membrane protein hemagglutinin (ha), which triggers membrane fusion and genome release under acidic conditions in the endosome. in addition to changes in the receptor binding domain, the acid stability of ha has been linked to the successful transmission of virus between avian and human hosts. however, to fully understand the connection between changes in ha and host tropism, additional ...201425320308
ifitm3 polymorphism rs12252-c restricts influenza a viruses.the ifitm3 polymorphism rs12252-c, which encodes an ifitm3 isoform (δ21 ifitm3) lacking 21 amino acids at the amino terminus, has been controversially associated with poor clinical outcomes in patients with h1n1 influenza a virus (iav) infections. in vitro studies have shown that δ21 ifitm3 loses its ability to restrict h1n1 iav. subsequent research has also revealed that tyrosine 20 is the key determinant for ifitm3 endocytic trafficking, which is essential for the efficient anti-viral activity ...201425314048
canine susceptibility to human influenza viruses (a/pdm 09h1n1, a/h3n2 and b).we investigated the infectivity and transmissibility of the human seasonal h3n2, pandemic (pdm) h1n1 (2009) and b influenza viruses in dogs. dogs inoculated with human seasonal h3n2 and pdm h1n1 influenza viruses exhibited nasal shedding and were seroconverted against the viruses; this did not occur in the influenza b virus-inoculated dogs. transmission of human h3n2 virus between dogs was demonstrated by observing nasal shedding and seroconversion in naïve dogs after contact with inoculated dog ...201525312584
characterization of human influenza viruses in lebanon during 2010-2011 and 2011-2012 post-pandemic seasons.to genetically characterize human influenza viruses and their susceptibilities to antivirals during two post-pandemic seasons in lebanon.201425301400
serological evidence for influenza virus infection in korean wild boars.serum samples from 1,011 wild boars hunted in 2012 were collected for serological surveillance for 4 subtypes (pandemic a (h1n1) 2009 and classical h1n1, h1n2 and h3n2) of swine influenza virus (siv). samples from 12 of the boars were identified as positive for siv (pandemic a (h1n1) 2009, n=9; classical h1n1, n=2; and h1n2, n=1) by a hemagglutination inhibition test (hi test) and a nucleoprotein (np)-based enzyme-linked immunosorbent assay (np-elisa). although the overall seroprevalence of siv ...201425298239
serial intervals of respiratory infectious diseases: a systematic review and analysis.the serial interval of an infectious disease represents the duration between symptom onset of a primary case and symptom onset of its secondary cases. a good evidence base for such values is essential, because they allow investigators to identify epidemiologic links between cases and serve as an important parameter in epidemic transmission models used to design infection control strategies. we reviewed the literature for available data sets containing serial intervals and for reported values of ...201425294601
a nonfusogenic antigen mimic of influenza hemagglutinin glycoproteins constituted with soluble full-length ha1 and truncated ha2 proteins expressed in e. coli.a novel method is proposed to produce a soluble recombinant antigen mimic, constituted with full-length ha1 and truncated ha2 individually expressed in e. coli, instead of a precursor form of hemagglutinin protein, that is similar to the naturally processed and disulfide-linked ha1/ha2 on the envelope of the influenza a virus strain x-31 (h3n2). a truncated ectodomain of ha2 subunit, ha2(23-185)/c137s, lacked two membrane-interacting sequences, i.e., the n-terminal fusion peptide as well as the ...201525288022
efficacy and safety of treatment with an anti-m2e monoclonal antibody in experimental human influenza.the efficacy of tcn-032, a human monoclonal antibody targeting a conserved epitope on m2e, was explored in experimental human influenza.201525281755
relative timing of influenza disease by age group.a detailed understanding of influenza movement in communities during yearly epidemics is needed to inform improved influenza control programs. we sought to determine the relative timing of influenza presentation and symptom onset by age group and influenza strain. prospective, laboratory-confirmed surveillance was performed over three moderate influenza seasons in emergency departments and inpatient settings of both medical centers in winston-salem, nc. influenza disease presented first in schoo ...201425280434
complete genome sequences of h3n2 canine influenza virus with the matrix gene from the pandemic a/h1n1 virus.we analyzed the complete genome sequence containing the 3' and 5' noncoding regions (ncrs) of h3n2 canine influenza virus (civ) with the matrix gene from the pandemic a/h1n1 virus, which will provide a better understanding of the pathogenesis, transmission, and evolution of variant civ.201425278543
in vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against clinical isolates of influenza virus in the japanese 2012-2013 season.the neuraminidase inhibitors (nais) oseltamivir phosphate (tamiflu(®)), zanamivir (relenza(®)), laninamivir octanoate (inavir(®)), and peramivir (rapiacta(®)) have been available for the treatment of influenza in japan since 2010. the emergence of resistant virus to any of the nais is a great concern for influenza treatment. to assess the extent of viral resistance, we measured the 50% inhibitory concentration (ic50) of each nai for influenza virus isolates in the 2012-2013 influenza season and ...201525277670
characterization of uncultivable bat influenza virus using a replicative synthetic virus.bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., ebola, sars-cov). recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. this discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the ha ...201425275541
the association of meningococcal disease with influenza in the united states, 1989-2009.prior influenza infection is a risk factor for invasive meningococcal disease. quantifying the fraction of meningococcal disease attributable to influenza could improve understanding of viral-bacterial interaction and indicate additional health benefits to influenza immunization.201425265409
comparative pathology of pigs infected with korean h1n1, h1n2, or h3n2 swine influenza a viruses.the predominant subtypes of swine influenza a virus (siv) in korea swine population are h1n1, h1n2, and h3n2. the viruses are genetically close to the classical u.s. h1n1 and triple-reassortant h1n2 and h3n2 viruses, respectively. comparative pathogenesis caused by korean h1n1, h1n2, and h3n2 siv was evaluated in this study.201425253051
synthesis and influenza virus inhibitory activities of carbosilane dendrimers peripherally functionalized with hemagglutinin-binding peptide.a series of carbosilane dendrimers uniformly functionalized with hemagglutinin (ha) binding peptide (sialic acid-mimic peptide, ala-arg-leu-pro-arg) was systematically synthesized, and their anti-influenza virus activity was evaluated. the carbosilane-based peptide dendrimers, unlike sialylated dendrimers, cannot be digested by virus neuraminidases. the peptide dendrimers exhibited intriguing biological activities depending on the form of their core frame, with a dumbbell-type peptide dendrimer ...201425249262
enhanced natural killer-cell and t-cell responses to influenza a virus during pregnancy.pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. although some data suggest that natural killer (nk)- and t-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. thus, we analyzed the responses of women that were pregnant (n = 21) versus those that were not (n = 29) immediately before inactivated influenza vaccination (iiv), 7 d after vaccination, and 6 wk postpar ...201425246558
multiple influenza a (h3n2) mutations conferring resistance to neuraminidase inhibitors in a bone marrow transplant recipient.immunocompromised patients are predisposed to infections caused by influenza virus. influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. this approach may promote the emergence of resistant strains. characterization of neuraminidase (na) inhibitor (nai)-resistant strains of influenza a virus is essential for documenting causes of resistance. in this ...201425246391
in vitro anti-influenza a activity of interferon (ifn)-λ1 combined with ifn-β or oseltamivir carboxylate.influenza viruses, which can cross species barriers and adapt to new hosts, pose a constant potential threat to human health. the influenza pandemic of 2009 highlighted the rapidity with which an influenza virus can spread worldwide. currently available antivirals have a number of limitations against influenza, and novel antiviral strategies, including novel drugs and drug combinations, are urgently needed. here, we evaluated the in vitro effects of interferon (ifn)-β, ifn-λ1, oseltamivir carbox ...201425245230
a plasmon-assisted fluoro-immunoassay using gold nanoparticle-decorated carbon nanotubes for monitoring the influenza virus.a plasmon-assisted fluoro-immunoassay (pafi) was developed for the detection of the influenza virus by using au nanoparticle (au np)-decorated carbon nanotubes (aucnts) that were synthesized using phytochemical composites at room temperature in deionized water. specific antibodies (abs) against the influenza virus were conjugated onto the surface of aucnts and cadmium telluride quantum dots (qds), which had a photoluminescence intensity that varied as a function of virus concentration and a dete ...201525240957
temporal insight into the natural generation of a new reassortant porcine influenza virus in a swine holding.the influenza a virus (iav) subtypes h1n1, h3n2 and h1n2 are the most prevalent subtypes in swine in italy. reassortant influenza a viruses subtypes in swine appeared in european pig population. in particular reassortant viruses carrying genome segment from the pandemic h1n1 (h1n1pdm) are reported in many european countries, including italy. in a 1000 sows farrow-to feeder farm, in northern italy, we isolated 10 iavs from recurrent episodes of respiratory disease in 45-70 days-old pigs from sept ...201425239679
using multiple linear regression and physicochemical changes of amino acid mutations to predict antigenic variants of influenza a/h3n2 viruses.among human influenza viruses, strain a/h3n2 accounts for over a quarter of a million deaths annually. antigenic variants of these viruses often render current vaccinations ineffective and lead to repeated infections. in this study, a computational model was developed to predict antigenic variants of the a/h3n2 strain. first, 18 critical antigenic amino acids in the hemagglutinin (ha) protein were recognized using a scoring method combining phi (ϕ) coefficient and information entropy. next, a pr ...201425227088
identification of genotypes of influenza a virus in malaysia.influenza is considered as an emerging disease until today. the present study was undertaken to determine the prevalent genotypes of influenza a virus in malaysia.201425225528
strain-specific antiviral activity of iminosugars against human influenza a viruses.drugs that target host cell processes can be employed to complement drugs that specifically target viruses, and iminosugar compounds that inhibit host α-glucosidases have been reported to show antiviral activity against multiple viruses. here the effect and mechanism of two iminosugar α-glucosidase inhibitors, n-butyl-deoxynojirimycin (nb-dnj) and n-nonyl-deoxynojirimycin (nn-dnj), on human influenza a viruses was examined.201425223974
comparative analysis of virulence of a novel, avian-origin h3n2 canine influenza virus in various host species.a novel avian-origin h3n2 canine influenza a virus (civ) that showed high sequence similarities in hemagglutinin and neuraminidase genes with those of non-pathogenic avian influenza viruses was isolated in our routine surveillance program in south korea. we previously reported that the pathogenicity of this strain could be reproduced in dogs and cats. in the present study, the host tropism of h3n2 civ was examined by experimental inoculation into several host species, including chickens, pigs, m ...201525218482
recombinant influenza h7 hemagglutinins induce lower neutralizing antibody titers in mice than do seasonal hemagglutinins.vaccines against avian influenza viruses often require high hemagglutinin (ha) doses or adjuvants to achieve serological titers associated with protection against disease. in particular, viruses of the h7 subtype frequently do not induce strong antibody responses following immunization.201425213778
antiviral activity of novel oseltamivir derivatives against some influenza virus strains.the aim of this study was to investigate the in vitro cytotoxicity of oseltamivir derivatives and determine their activity against a/h1n1/pr/8/34 and a/h3n2/hongkong/8/68 - strains of influenza virus. antiviral activity of these compounds was determined by using two methods. mtt staining was used to assess the viability of mdck cells infected with influenza viruses and treated with various concentrations of drugs. in parallel, the effect of drugs on viral replication was assessed using the hemag ...201425210935
effectiveness of post-exposition prophylaxis with oseltamivir in nursing homes: a randomised controlled trial over four seasons.oseltamivir has been registered for use as post-exposition prophylaxis (pep) following exposure to influenza, based on studies among healthy adults. effectiveness among frail elderly nursing home populations still needs to be properly assessed.201425210532
characterization of a broadly neutralizing monoclonal antibody that targets the fusion domain of group 2 influenza a virus hemagglutinin.due to continuous changes to its antigenic regions, influenza viruses can evade immune detection and cause a significant amount of morbidity and mortality around the world. influenza vaccinations can protect against disease but must be annually reformulated to match the current circulating strains. in the development of a broad-spectrum influenza vaccine, the elucidation of conserved epitopes is paramount. to this end, we designed an immunization strategy in mice to boost the humoral response ag ...201425210195
emerging viral respiratory tract infections--environmental risk factors and transmission.the past decade has seen the emergence of several novel viruses that cause respiratory tract infections in human beings, including middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia, an h7n9 influenza a virus in eastern china, a swine-like influenza h3n2 variant virus in the usa, and a human adenovirus 14p1 also in the usa. mers-cov and h7n9 viruses are still a major worldwide public health concern. the pathogenesis and mode of transmission of mers-cov and h7n9 influenza a v ...201425189350
surveillance for emerging respiratory viruses.several new viral respiratory tract infectious diseases with epidemic potential that threaten global health security have emerged in the past 15 years. in 2003, who issued a worldwide alert for an unknown emerging illness, later named severe acute respiratory syndrome (sars). the disease caused by a novel coronavirus (sars-cov) rapidly spread worldwide, causing more than 8000 cases and 800 deaths in more than 30 countries with a substantial economic impact. since then, we have witnessed the emer ...201425189347
severity of clinical disease and pathology in ferrets experimentally infected with influenza viruses is influenced by inoculum volume.ferrets are a valuable model for influenza virus pathogenesis, virus transmission, and antiviral therapy studies. however, the contributions of the volume of inoculum administered and the ferret's respiratory tract anatomy to disease outcome have not been explored. we noted variations in clinical disease outcomes and the volume of inoculum administered and investigated these differences by administering two influenza viruses (a/california/07/2009 [h1n1 pandemic] and a/minnesota/11/2010 [h3n2 var ...201425187553
generation and characterization of influenza a viruses with altered polymerase fidelity.genetic diversity of influenza a viruses (iav) acquired through the error-prone rna-dependent rna polymerase (rdrp) or through genetic reassortment enables perpetuation of iav in humans through epidemics or pandemics. here, to assess the biological significance of genetic diversity acquired through rdrp, we characterize an iav fidelity variant derived from passaging a seasonal h3n2 virus in the presence of ribavirin, a purine analogue that increases guanosine-to-adenosine mutations. we demonstra ...201425183443
an efficient genome sequencing method for equine influenza [h3n8] virus reveals a new polymorphism in the pa-x protein.h3n8 equine influenza virus (eiv) has caused disease outbreaks in horses across the world since its first isolation in 1963. however, unlike human, swine and avian influenza, there is relatively little sequence data available for this virus. the majority of published sequences are for the segment encoding haemagglutinin (ha), one of the two surface glycoproteins, making it difficult to study the evolution of the other gene segments and determine the level of reassortment occurring between sub-li ...201425183201
a population prevalence study on influenza infection in dogs in southern italy.despite several data on influenza infection in dogs, the first natural outbreak of canine influenza virus, closely related to h3n8 equine subtype, dates back to 2004 in florida. subsequent studies highlighted the role of dogs in adaptation of h5n1 to mammals and the susceptibility of dogs to different subtypes of influenza. a prevalence study was carried out on 562 sera collected from pet and kennel dogs in the south of italy. a c-elisa test was employed and c-elisa-positive, c-elisa-doubtful an ...201425180843
t-cell-mediated cross-strain protective immunity elicited by prime-boost vaccination with a live attenuated influenza vaccine.antigenic drift and shift of influenza viruses require frequent reformulation of influenza vaccines. in addition, seasonal influenza vaccines are often mismatched to the epidemic influenza strains. this stresses the need for a universal influenza vaccine.201425172265
influenza m2 virus-like particles confer a broader range of cross protection to the strain-specific pre-existing immunity.immunity in humans with annual vaccination does not provide effective protection against antigenically distinct strains. as an approach to improve cross-protection in the presence of pre-existing strain-specific immunity, we investigated the efficacy of heterologous and heterosubtypic protection in previously vaccinated mice at earlier times after subsequent immunization with conserved-antigenic target influenza m2 ectodomain (m2e) virus-like particle vaccine (m2e5× vlp). immunization of mice wi ...201425171841
infection of influenza virus neuraminidase-vaccinated mice with homologous influenza virus leads to strong protection against heterologous influenza viruses.vaccination is the best measure to prevent influenza pandemics. here, we studied the protective effect against heterologous influenza viruses, including a/reassortant/nymc x-179a (ph1n1), a/chicken/henan/12/2004 (h5n1), a/chicken/jiangsu/7/2002 (h9n2) and a/guizhou/54/89×a/pr/8/34 (a/guizhou-x) (h3n2), in mice first vaccinated with a dna vaccine of haemagglutinin (ha) or neuraminidase (na) of a/pr/8/34 (pr8) and then infected with the homologous virus. we showed that pr8 ha or na vaccination bot ...201425170051
influenza polymerase encoding mrnas utilize atypical mrna nuclear export.influenza is a segmented negative strand rna virus. each rna segment is encapsulated by influenza nucleoprotein and bound by the viral rna dependent rna polymerase (rdrp) to form viral ribonucleoproteins responsible for rna synthesis in the nucleus of the host cell. influenza transcription results in spliced mrnas (m2 and ns2), intron-containing mrnas (m1 and ns1), and intron-less mrnas (ha, na, np, pb1, pb2, and pa), all of which undergo nuclear export into the cytoplasm for translation. most c ...201425168591
early activation of map kinases by influenza a virus x-31 in murine macrophage cell lines.early molecular responses to influenza a (flua) virus strain a/x-31 h3n2 in macrophages were explored using j774.a1 and raw 264.7 murine cell lines. nf-kappa b (nfκb) was reported to be central to flua host-response in other cell types. our data showed that flua activation of the classical nfκb dependent pathway in these macrophages was minimal. regulator proteins, ikappab-alpha and -beta (iκbα, iκbβ), showed limited degradation peaking at 2 h post flua exposure and p65 was not observed to trans ...201425166426
cleavage of hemagglutinin-bearing lentiviral pseudotypes and their use in the study of influenza virus persistence.influenza a viruses (iavs) are a major cause of infectious respiratory human diseases and their transmission is dependent upon the environment. however, the role of environmental factors on iav survival outside the host still raises many questions. in this study, we used lentiviral pseudotypes to study the influence of the hemagglutinin protein in iav survival. high-titered and cleaved influenza-based lentiviral pseudoparticles, through the use of a combination of two proteases (hat and tmprss2) ...201425166303
live attenuated and inactivated influenza vaccines in children.live attenuated influenza vaccine (laiv) and inactivated influenza vaccine (iiv) are available for children. local and systemic immunity induced by laiv followed a month later by laiv and iiv followed by laiv were investigated with virus recovery after laiv doses as surrogates for protection against influenza on natural exposure.201525165161
cellular and humoral cross-immunity against two h3n2v influenza strains in presumably unexposed healthy and hiv-infected subjects.human cases of infection due to a novel swine-origin variant of influenza a virus subtype h3n2 (h3n2v) have recently been identified in the united states. pre-existing humoral and cellular immunity has been recognized as one of the key factors in limiting the infection burden of an emerging influenza virus strain, contributing to restrict its circulation and to mitigate clinical presentation. aim of this study was to assess humoral and cell-mediated cross immune responses to h3n2v in immuno-comp ...201425162670
deep sequencing reveals the eight facets of the influenza a/hongkong/1/1968 (h3n2) virus cap-snatching process.the influenza a virus rna polymerase cleaves the 5' end of host pre-mrnas and uses the capped rna fragments as primers for viral mrna synthesis. we performed deep sequencing of the 5' ends of viral mrnas from all genome segments transcribed in both human (a549) and mouse (m-1) cells infected with the influenza a/hongkong/1/1968 (h3n2) virus. in addition to information on rna motifs present, our results indicate that the host primers are divergent between the viral transcripts. we observed differ ...201425154590
swine-to-human transmission of influenza a(h3n2) virus at agricultural fairs, ohio, usa, 2012.agricultural fairs provide an opportunity for bidirectional transmission of influenza a viruses. we sought to determine influenza a virus activity among swine at fairs in the united states. as part of an ongoing active influenza a virus surveillance project, nasal swab samples were collected from exhibition swine at 40 selected ohio agricultural fairs during 2012. influenza a(h3n2) virus was isolated from swine at 10 of the fairs. according to a concurrent public health investigation, 7 of the 1 ...201425148572
characterization of variations in pb2, ns1, m, neuraminidase and hemagglutinin of influenza a (h3n2) viruses in iran.in the influenza a viruses, neuraminidase (na), hemagglutinin (ha), pb2, ns1 and m are responsible for the disease pathogenicity. the mechanism of pathogenicity differs among these viruses. binding of host proteases by the viral na, sequence of ha in the cleavage and receptor-binding sites, number of oligosaccharide side chains of ha, shortening of na, and substitutions in pb2, ns1 and m genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses.201425147684
desc1 and mspl activate influenza a viruses and emerging coronaviruses for host cell entry.the type ii transmembrane serine protease (ttsp) tmprss2 cleaves and activates the influenza virus and coronavirus surface proteins. expression of tmprss2 is essential for the spread and pathogenesis of h1n1 influenza viruses in mice. in contrast, h3n2 viruses are less dependent on tmprss2 for viral amplification, suggesting that these viruses might employ other ttsps for their activation. here, we analyzed ttsps, reported to be expressed in the respiratory system, for the ability to activate in ...201425122802
computational prediction of vaccine strains for human influenza a (h3n2) viruses.human influenza a viruses are rapidly evolving pathogens that cause substantial morbidity and mortality in seasonal epidemics around the globe. to ensure continued protection, the strains used for the production of the seasonal influenza vaccine have to be regularly updated, which involves data collection and analysis by numerous experts worldwide. computer-guided analysis is becoming increasingly important in this problem due to the vast amounts of generated data. we here describe a computation ...201425122778
[genetic characteristics of influenza a/h3n2 virus neuraminidase gene: a survey from 2010 to 2012 in qinghai province, china].this study aims to perform a survey of genetic variation in neuraminidase (na) gene of influenza a/h3n2 virus, as well as related resistance to na inhibitors, in qinghai province of china, 2010 to 2012. strains of influenza a/h3n2 isolated during an influenza survey from 2010 to 2012 in qinghai were enrolled by random sampling. viral rna was extracted and amplified by rt-pcr. purified pcr products were sequenced thereafter. genetic analysis of nucleic acid and the derived amino acid sequences wa ...201425118381
evolution of oseltamivir resistance mutations in influenza a(h1n1) and a(h3n2) viruses during selection in experimentally infected mice.the evolution of oseltamivir resistance mutations during selection through serial passages in animals is still poorly described. herein, we assessed the evolution of neuraminidase (na) and hemagglutinin (ha) genes of influenza a/wsn/33 (h1n1) and a/victoria/3/75 (h3n2) viruses recovered from the lungs of experimentally infected balb/c mice receiving suboptimal doses (0.05 and 1 mg/kg of body weight/day) of oseltamivir over two generations. the traditional phenotypic and genotypic methods as well ...201425114143
pi3k/akt signaling pathway modulates influenza virus induced mouse alveolar macrophage polarization to m1/m2b.macrophages polarized to m1 (pro-inflammation) or m2 (anti-inflammation) phenotypes in response to environmental signals. in this study, we examined the polarization of alveolar macrophage (am), following induction by different influenza virus strains (st169 (h1n1), st602 (h3n2) and hkg9 (h9n2)). macrophages from other tissues or cell line exert alternative responding pattern, and am is necessary for investigating the respiratory system. am polarized toward the m1 phenotype after 4 hours of infe ...201425105760
induction of cd8 t cell heterologous protection by a single dose of single-cycle infectious influenza virus.the effector functions of specific cd8 t cells are crucial in mediating influenza heterologous protection. however, new approaches for influenza vaccines that can trigger effective cd8 t cell responses have not been extensively explored. we report here the generation of single-cycle infectious influenza virus that lacks a functional hemagglutinin (ha) gene on an x31 genetic background and demonstrate its potential for triggering protective cd8 t cell immunity against heterologous influenza virus ...201425100831
inhibitory potency of flavonoid derivatives on influenza virus neuraminidase.the constant risk of emerging new influenza virus strains that are resistant to established inhibitors like oseltamivir leaves influenza neuraminidase (na) a prominent target for drug design. the inhibitory activity of several flavonoid derivatives was experimentally tested in comparison to oseltamivir for the na expressed by the seasonal influenza virus strains a/california/7/09 (a(h1n1)pdm09), a/perth/16/09 (a(h3n2)), and b/brisbane/60/08. ic50 values of polyphenols confirmed moderate inhibiti ...201425096296
the effectiveness of influenza vaccination in preventing hospitalizations in children in hong kong, 2009-2013.influenza vaccination is widely recommended every year to protect individuals against influenza virus infection and illness. there are few published estimates of influenza vaccine effectiveness against hospitalization in children or from subtropical regions.201425092636
influenza vaccine effectiveness against medically-attended influenza illness during the 2012-2013 season in beijing, china.influenza vaccine coverage remains low in china, and there is limited information on the preventive value of local vaccination programs.201425092635
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