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a predictive fitness model for influenza.the seasonal human influenza a/h3n2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. two factors are shown to determ ...201424572367
live attenuated influenza vaccine enhances colonization of streptococcus pneumoniae and staphylococcus aureus in mice.community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. what has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (laivs). using a mouse-adapted laiv against influenza a (h3n2) virus carrying the same mutations as the human flumist vaccine, we find that laiv vacc ...201424549845
substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza a h3n2 viruses in u.s. swine.swine influenza a virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. the hemagglutinin (ha) protein is the primary target of protective immune responses and the major component in swine influenza a vaccines. however, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in huma ...201424522915
the duration of fever and other symptoms after the initiation of laninamivir octanoate hydrate in the japanese 2011-2012 influenza season.laninamivir octanoate hydrate (laninamivir) is a long-acting, single inhalation neuraminidase inhibitor that was approved in japan in 2010 for the treatment of influenza a and b virus infection. we investigated the duration of fever and other symptoms after the initiation of laninamivir in the japanese 2011-2012 influenza season. virus isolation was done and the 50% inhibitory concentration (ic₅₀) was measured for the virus isolates at days 1 and 5. for 211 patients (a(h3n2): 190, b: 21), the me ...201424486167
intranasal vaccination promotes detrimental th17-mediated immunity against influenza infection.influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. we evaluated the efficacy of a synthetic toll-like receptor 4 agonist crx-601 as an adjuvant for enhancing vaccine-induced protection against influenza infectio ...201424465206
emergence of truncated pb1-f2 protein of h3n2 influenza virus during its epidemic period in jiangsu province, china.pb1-f2 protein has been proven to increase the pathogenicity of influenza a virus (iav) strains in primary infection and in secondary bacterial infection. it can also regulate the activity of viral polymerase. however, it was shown in another retrospective study that a portion of iavs do not express full-length pb1-f2 protein during virus development; different kinds of stop codons cause exits in the open reading frames and form pb1-f2 gene products with the corresponding genotypes. truncated pb ...201424762594
akt inhibitor mk2206 prevents influenza ph1n1 virus infection in vitro.the influenza ph1n1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. here we show that the akt inhibitor mk2206 blocks influenza ph1n1 virus infection in vitro. in particular, at noncytotoxic concentrations, mk2206 alters akt signaling and inhibits endocytic uptake of the virus. interestingly, mk2206 is unable to inhibit h3n2, ...201424752266
influenza a subtype h3 viruses in feral swine, united states, 2011-2012.to determine whether, and to what extent, influenza a subtype h3 viruses were present in feral swine in the united states, we conducted serologic and virologic surveillance during october 2011-september 2012. these animals were periodically exposed to and infected with a(h3n2) viruses, suggesting they may threaten human and animal health.201424751326
development of a reverse transcription loop-mediated isothermal amplification assay for the rapid diagnosis of avian influenza a (h7n9) virus infection.a genetic diagnosis system for detecting avian influenza a (h7n9) virus infection using reverse transcription-loop-mediated isothermal amplification (rt-lamp) technology was developed. the rt-lamp assay showed no cross-reactivity with seasonal influenza a (h3n2 and h1n1pdm09) or influenza b viruses circulating in humans or with avian influenza a (h5n1) viruses. the sensitivity of the rt-lamp assay was 42.47 copies/reaction. considering the high specificity and sensitivity of the assay for detect ...201424747008
intrahost dynamics of influenza virus reassortment.the segmented nature of the influenza virus genome allows reassortment between coinfecting viruses. this process of genetic exchange vastly increases the diversity of circulating influenza viruses. the importance of reassortment to public health is clear from its role in the emergence of a number of epidemiologically important viruses, including novel pandemic and epidemic strains. to gauge its impact on within-host genomic variation, we tracked reassortment in coinfected guinea pigs over time a ...201424741099
analysis of the acute-phase protein response in pigs to clinical and subclinical infection with h3n2 swine influenza virus.swine influenza (si) is a contagious, important respiratory disease. diagnosis of si is based on the clinical signs, confirmed by the detection of viral rna or specific antibodies. however, the infection is much more frequent than the disease.201424734294
duration of the protective immune response after prime and booster vaccination of yearlings with a live modified cold-adapted viral vaccine against equine influenza.we previously created a live vaccine against equine influenza based the new reassortant cold-adapted (ca) strain a/hk/otar/6:2/2010. the live vaccine contains surface proteins (ha, na) from the wild-type virus a/equine/otar/764/2007 (н3n8; american lineage florida clade 2), and internal proteins (pb2, pb1, pa, np, m, ns) from the attenuated ca donor virus a/hong kong/1/68/162/35ca (h3n2). to determine the safety and duration of the protective immune responses, 90 yearlings were intranasally vacc ...201424726250
conserved neutralizing epitope at globular head of hemagglutinin in h3n2 influenza viruses.neutralizing antibodies that target the hemagglutinin of influenza virus either inhibit binding of hemagglutinin to cellular receptors or prevent the low-ph-induced conformational change in hemagglutinin required for membrane fusion. in general, the former type of antibody binds to the globular head formed by ha1 and has narrow strain specificity, while the latter type binds to the stem mainly formed by ha2 and has broad strain specificity. in the present study, we analyzed the epitope and funct ...201424719430
receptor mimicry by antibody f045-092 facilitates universal binding to the h3 subtype of influenza virus.influenza viruses present a significant health challenge each year, as in the h3n2 epidemic of 2012-2013. here we describe an antibody, f045-092, that possesses broadly neutralizing activity against the entire h3 subtype and accommodates the natural variation and additional glycosylation in all strains tested from 1963 to 2011. crystal structures of f045-092 in complex with has from 1975 and 2011 h3n2 viruses reveal the structural basis for its neutralization breadth through insertion of its 23- ...201424717798
a broadly neutralizing human monoclonal antibody directed against a novel conserved epitope on the influenza virus h3 hemagglutinin globular head.most neutralizing antibodies elicited during influenza virus infection or vaccination target immunodominant, variable epitopes on the globular head region of hemagglutinin (ha), which leads to narrow strain protection. in this report, we describe the properties of a unique anti-ha monoclonal antibody (mab), d1-8, that was derived from human b cells and exhibits potent, broad neutralizing activity across antigenically diverse influenza h3 subtype viruses. based on selection of escape variants, we ...201424696468
full-genome sequences of influenza h3n2 virus strains isolated from finnish patients during the 2012-2013 epidemic season.here, we sequenced 10 influenza a(h3n2) virus genomes isolated from finnish patients diagnosed with flu-like illness during the 2012-2013 influenza season. the alignment showed a high number of amino acid substitutions (238 in total) in only 10 samples, proving that a high mutation rate exists in seasonal influenza a viruses.201424675845
comparison of the clinical effectiveness of zanamivir and laninamivir octanoate for children with influenza a(h3n2) and b in the 2011-2012 season.to evaluate the clinical effectiveness of the two inhaled neuraminidase inhibitors (nais), zanamivir (zn) and laninamivir octate (lo), for influenza a(h3n2) and b virus infections.201423953886
no serological evidence of influenza a h1n1pdm09 virus infection as a contributing factor in childhood narcolepsy after pandemrix vaccination campaign in finland.narcolepsy cataplexy syndrome, characterised by excessive daytime sleepiness and cataplexy, is strongly associated with a genetic marker, human leukocyte antigen (hla) dqb1*06:02. a sudden increase in the incidence of childhood narcolepsy was observed after vaccination with as03-adjuvanted pandemrix influenza vaccine in finland at the beginning of 2010. here, we analysed whether the coinciding influenza a h1n1pdm pandemic contributed, together with the pandemrix vaccination, to the increased inc ...201323950869
[chemical consitituents from root of isatis indigotica].thirty-three compounds were isolated from the root decoction of isatis indigotica by using a combination of various chromatographic techniques including silica gel, macroporous adsorbent resin, sephadex lh-20, and reversed-phase hplc. their structures were elucidated by spectroscopic data as (+)-dehydrovomifoliol (1), (s)-(+)-abscisic acid (2), vomifoliol (3), cyclo (l-phe-l-leu) (4), cyclo(l-phe-l-tyr) (5), cyclo(l-tyr-l-leu) (6), cyclo(l-pro-l-tyr) (7), evofolin b (8), (+)-syringaresinol (9), ...201323944031
antiviral spirooliganones a and b with unprecedented skeletons from the roots of illicium oligandrum.two novel spirooliganones a (1) and (2), a pair of spiro carbon epimers, with a rare dioxaspiro skeleton were isolated from the roots of illicium oligandrum. the structures were fully determined by spectroscopic analysis and chemical methods, especially modified mosher's method, and x-ray diffraction analysis. spirooliganone b was found to exhibit more potent activities against coxsackie virus b3 and influenza virus a (h3n2) (ic50 3.70-5.05 μm) than spirooliganone a. the biosynthetic pathway inv ...201323937631
emergence of a c-terminal seven-amino-acid elongation of ns1 in around 1950 conferred a minor growth advantage to former seasonal influenza a viruses.influenza a viruses circulating in humans from ∼1950 to ∼1987 featured a nonstructural (ns1) protein with a c-terminal extension of seven amino acids. the biological significance of this ns1 elongation remained elusive. we observed that replication kinetics of the wild-type virus a/hong kong/01/68 (h3n2) and a mutant encoding a truncated ns1 were indistinguishable in most experimental systems. however, wild-type virus outcompeted the mutant during mixed infections, suggesting that the ns1 extens ...201323926347
preliminary crystallographic analysis of neuraminidase n2 from a new influenza a virus.influenza virus is a major viral respiratory pathogen that causes yearly epidemics in temperate climates. the h3n2 subtype is one of the major causative agents of severe epidemics and plays a critical role in vaccine development. the neuraminidase (na) inhibitors oseltamivir and zanamivir are two commercially available na-targeted competitive antiviral drugs. however, their effectiveness has been compromised by the rapid emergence of resistance. q136k is a novel mutation in na which confers resi ...201323908028
[virological characterization of influenza a(h3n2) virus in mainland china during 2011-2012].to study the prevalence and variation of influenza a(h3n2) viruses, the antigenic and genetic characteristics of influenza a(h3n2) viruses circulating in mainland china during april 2011 to march 2012 were analyzed. the results showed that influenza a(h3n2) viruses increased gradually since 2012 and became the dominant strain since march. the viruses were antigenically closely related to the vaccine strain a/per/16/09 (87.2%) and the representative virus a/fj/196/09 (76.0%) in mainland china. th ...201323905468
selection of h3 avian influenza viruses with saα2,6gal receptor specificity in pigs.avian influenza viruses possess hemagglutinin (ha) which preferentially bind to the sialic acid α2,3-galactose sialyloligosaccharides (saα2,3gal) receptor. in contrast, human influenza viruses bind to sialic acid α2,6-galactose sialyloligosaccharides (saα2,6gal). the a/hong kong/68 (h3n2) virus preferentially binds to saα2,6gal, although its ha gene was derived from an avian influenza virus strain. to elucidate the mechanisms behind acquisition of binding specificity for the human-type receptor, ...201323891155
gestational flu exposure induces changes in neurochemicals, affiliative hormones and brainstem inflammation, in addition to autism-like behaviors in mice.the prevalence of neurodevelopmental disorders such as autism is increasing, however the etiology of these disorders is unclear and thought to involve a combination of genetic, environmental and immune factors. a recent epidemiological study found that gestational viral exposure during the first trimester increases risk of autism in offspring by twofold. in mice gestational viral exposures alter behavior of offspring, but the biological mechanisms which underpin these behavioral changes are uncl ...201323880236
observations of immuno-gold conjugates on influenza viruses using waveguide-mode sensors.gold nanoparticles were conjugated to an antibody (immuno-aunp) against a/udorn/307/1972 (h3n2) influenza virus to detect viruses on a sensing plate designed for an evanescent field-coupled waveguide-mode sensor. experiments were conducted using human influenza a/h3n2 strains, and immuno-aunp could detect 8×10(5) pfu/ml (40 pg/µl) intact a/udorn/307/1972 and 120 pg/µl a/brisbane/10/2007. furthermore, increased signal magnitude was achieved in the presence of non-ionic detergent, as the virtual d ...201323874887
mitochondrial proteomic analysis of human host cells infected with h3n2 swine influenza virus.swine influenza viruses (siv) are zoonotic pathogens that pose a potential threat to human health. in this study, we analyzed the differential mitochondrial proteomes of h3n2 siv-infected human lung a549 cells using two-dimensional gel electrophoresis (2-de) followed by matrix-assisted laser desorption ionization time-of-flight/time-of-flight (maldi-tof/tof) analysis. in the comparative analysis, 24 altered proteins (13 upregulated and 11 downregulated) were identified in the mitochondria of h3n ...201323856606
pathogenesis and transmission of avian influenza a (h7n9) virus in ferrets and mice.on 29 march 2013, the chinese center for disease control and prevention confirmed the first reported case of human infection with an avian influenza a(h7n9) virus. the recent human infections with h7n9 virus, totalling over 130 cases with 39 fatalities to date, have been characterized by severe pulmonary disease and acute respiratory distress syndrome (ards). this is concerning because h7 viruses have typically been associated with ocular disease in humans, rather than severe respiratory disease ...201323842497
single hemagglutinin mutations that alter both antigenicity and receptor binding avidity influence influenza virus antigenic clustering.the hemagglutination inhibition (hai) assay is the primary measurement used for identifying antigenically novel influenza virus strains. hai assays measure the amount of reference sera required to prevent virus binding to red blood cells. receptor binding avidities of viral strains are not usually taken into account when interpreting these assays. here, we created antigenic maps of human h3n2 viruses that computationally account for variation in viral receptor binding avidities. these new antige ...201323824816
efficacy in pigs of inactivated and live attenuated influenza virus vaccines against infection and transmission of an emerging h3n2 similar to the 2011-2012 h3n2v.vaccines provide a primary means to limit disease but may not be effective at blocking infection and pathogen transmission. the objective of the present study was to evaluate the efficacy of commercial inactivated swine influenza a virus (iav) vaccines and experimental live attenuated influenza virus (laiv) vaccines against infection with h3n2 virus and subsequent indirect transmission to naive pigs. the h3n2 virus evaluated was similar to the h3n2v detected in humans during 2011-2012, which was ...201323824815
a microbead-incorporated centrifugal sample pretreatment microdevice.in this study, we present a novel bead-incorporated centrifugal sample pretreatment microdevice to purify influenza a h3n2 viral rna. simple revolution per minute (rpm) control can lead to rna capture on a bead-bed, and the sequential loading of a washing solution and an elution solution. tetraethoxy orthosilicate (teos)-treated glass microbeads were utilized as a capture matrix. the sample pretreatment microdevice consists of four reservoirs for storing an rna sample, a washing solution, an elu ...201323824467
using sequence data to infer the antigenicity of influenza virus.the efficacy of current influenza vaccines requires a close antigenic match between circulating and vaccine strains. as such, timely identification of emerging influenza virus antigenic variants is central to the success of influenza vaccination programs. empirical methods to determine influenza virus antigenic properties are time-consuming and mid-throughput and require live viruses. here, we present a novel, experimentally validated, computational method for determining influenza virus antigen ...201323820391
different drug-resistant influenza a(h3n2) variants in two immunocompromised patients treated with oseltamivir during the 2011-2012 influenza season in italy.monitoring the emergence of drug-resistant influenza variants is crucial in influenza surveillance programs.201323810646
influenza virus a(h3n2) strain isolated from cerebrospinal fluid from a patient presenting myelopathy post infectious.neurological involvement during influenza infection has been described during epidemics and is often consistent with serious sequelae or death.201323809474
[laboratory diagnostics in evaluation of acute respiratory viral infection morbidity in 2010 - 2011 epidemic season].study of etiological structure of arvi and evaluation of acute respiratory virus infection morbidity in 2010 - 2011 epidemic season taking into account the data of laboratory diagnostics by method of polymerase chain reaction with hybridization-fluorescent detection.201323805649
transmissibility of variant influenza from swine to humans: a modeling approach.respiratory illness was reported among humans and swine at an agricultural fair in 2011; 3 human infections with an influenza a(h3n2) variant (h3n2v) virus were confirmed. using epidemiologic investigation data, we sought to estimate h3n2v transmissibility from swine to humans.201323794727
the emergence of influenza a (h3n2)v virus: what we learned from the first wave. 201323794725
human h3n2 influenza viruses isolated from 1968 to 2012 show varying preference for receptor substructures with no apparent consequences for disease or spread.it is generally accepted that human influenza viruses bind glycans containing sialic acid linked α2-6 to the next sugar, that avian influenza viruses bind glycans containing the α2-3 linkage, and that mutations that change the binding specificity might change the host tropism. we noted that human h3n2 viruses showed dramatic differences in their binding specificity, and so we embarked on a study of representative human h3n2 influenza viruses, isolated from 1968 to 2012, that had been isolated an ...201323805213
myopericarditis and exertional rhabdomyolysis following an influenza a (h3n2) infection.acute myopericarditis and exertional rhabdomyolysis, two uncommon but well-described diseases with potentially life-threatening effects, are generally considered as independent clinical entities. however, they may in fact be pathophysiologically related under certain circumstances. this is the first ever report of influenza myopericarditis provoked by exertional rhabdomyolysis to the best of our knowledge.201323786640
analytical sensitivity of seven point-of-care influenza virus detection tests and two molecular tests for detection of avian origin h7n9 and swine origin h3n2 variant influenza a viruses. 201323784125
[phylogenetic analysis and genotyping of a/h3n2 influenza viruses isolated from patients hospitalised with influenza-like illness symptoms in the na bulovce hospital in the season 2011/2012].influenza a virus is an important cause of acute respiratory infections (ari). clinical manifestations of ari vary from mild or moderate to life-threatening conditions requiring intensive care. given the segmented genome, a large natural reservoir of other influenza virus subtypes, and antibody selection pressure in the population, the virus is variable and genetically unstable. the phylogenetic analysis and genotyping of a/h3n2 influenza viruses isolated from patients hospitalised with influenz ...201323768089
[avian influenza virus subtype h9n2 replicates in human lung tissues].avian influenza virus subtype h9n2 has been circulating in multiple terrestrial birds and repeatedly infecting mammals, including swines and humans to pose a significant threat to public health. the cross-species infection of human, replication activity and tissue tropism of avian influenza virus h9n2 was evaluated in this study. the results showed that surgically removed human lung tissue samples were infected ex vivo by avian influenza virus subtype h9n2 (ck/gx/1875/04, ck/gx/187/05) and seaso ...201323757854
mutations of two transmembrane cysteines of hemagglutinin (ha) from influenza a h3n2 virus affect ha thermal stability and fusion activity.influenza a h3n2 virus caused 1968 hong kong influenza pandemic, and has since been one of the most prevalent seasonal influenza viruses in global populations, representing a credible pandemic candidate in future. previous studies have established that the hemagglutinin (ha) protein is the predominant antigen and executes receptor binding and membrane fusion. homologous sequence analysis of all ha subtypes of influenza viruses revealed that two cysteine residues (540 and 544) are uniquely presen ...201323749101
simplified large-scale sanger genome sequencing for influenza a/h3n2 virus.the advent of next-generation sequencing technologies and the resultant lower costs of sequencing have enabled production of massive amounts of data, including the generation of full genome sequences of pathogens. however, the small genome size of the influenza virus arguably justifies the use of the more conventional sanger sequencing technology which is still currently more readily available in most diagnostic laboratories.201323741393
virus-like particle vaccine protects against h3n2 canine influenza virus in dog.in the present study, virus-like particles (vlps) were evaluated as a candidate veterinary vaccine against canine influenza virus (civ) subtype h3n2. specific pathogen-free (spf) beagle dogs received a single injection of a vlp vaccine containing hemagglutinin (ha) and m1 protein of civ h3n2 (h3 ha vlp). the vaccine was tested at 3 different doses with an adjuvant and 1 dose without an adjuvant. to evaluate the immunogenicity and protective efficacy of the h3 ha vlp vaccine, we performed hemaggl ...201323707159
vitamin c is an essential factor on the anti-viral immune responses through the production of interferon-α/β at the initial stage of influenza a virus (h3n2) infection.l-ascorbic acid (vitamin c) is one of the well-known anti-viral agents, especially to influenza virus. since the in vivo anti-viral effect is still controversial, we investigated whether vitamin c could regulate influenza virus infection in vivo by using gulo (-/-) mice, which cannot synthesize vitamin c like humans. first, we found that vitamin c-insufficient gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (h3n2/hongkong). viral titers in the lung of vitami ...201323700397
a comparison of the clinical and epidemiological characteristics of adult patients with laboratory-confirmed influenza a or b during the 2011-2012 influenza season in korea: a multi-center study.during the 2011/2012 winter influenza season in the republic of korea, influenza a (h3n2) was the predominant virus in the first peak period of influenza activity during the second half of january 2012. on the other hand, influenza b was the predominant virus in the second peak period of influenza activity during the second half of march 2012. the objectives of this study were to compare the clinical and epidemiological characteristics of patients with laboratory-confirmed influenza a or influen ...201323671624
predicting hotspots for influenza virus reassortment.the 1957 and 1968 influenza pandemics, each of which killed ≈1 million persons, arose through reassortment events. influenza virus in humans and domestic animals could reassort and cause another pandemic. to identify geographic areas where agricultural production systems are conducive to reassortment, we fitted multivariate regression models to surveillance data on influenza a virus subtype h5n1 among poultry in china and egypt and subtype h3n2 among humans. we then applied the models across asi ...201323628436
a novel canine influenza h3n2 virus isolated from cats in an animal shelter.the interspecies transmission of avian-origin h3n2 canine influenza virus (civ) to dogs was first reported in 2007. the present study characterized a novel civ h3n2 isolated from cats in an animal shelter. a comparative analysis of the deduced amino acid sequences of the a/canine/korea/cy009/2010(h3n2) (cy009) and a/feline/korea/fy028/2010 (h3n2) (fy028) strains isolated from dogs and cats, respectively, in the animal shelter identified point mutations in 18 amino acid positions within eight vir ...201323618838
nox1 oxidase suppresses influenza a virus-induced lung inflammation and oxidative stress.influenza a virus infection is an ongoing clinical problem and thus, there is an urgent need to understand the mechanisms that regulate the lung inflammation in order to unravel novel generic pharmacological strategies. evidence indicates that the nox2-containing nadph oxidase enzyme promotes influenza a virus-induced lung oxidative stress, inflammation and dysfunction via ros generation. in addition, lung epithelial and endothelial cells express the nox1 isoform of nadph oxidase, placing this e ...201323577160
2011-12 seasonal influenza vaccines effectiveness against confirmed a(h3n2) influenza hospitalisation: pooled analysis from a european network of hospitals. a pilot study.influenza vaccination strategies aim at protecting high-risk population from severe outcomes. estimating the effectiveness of seasonal vaccines against influenza related hospitalisation is important to guide these strategies. large sample size is needed to have precise estimate of influenza vaccine effectiveness (ive) against severe outcomes. we assessed the feasibility of measuring seasonal ive against hospitalisation with laboratory confirmed influenza through a network of 21 hospitals in the ...201323565159
role of human toll-like receptors in naturally occurring influenza a infections.we investigated the roles of toll-like receptors (tlrs) in naturally occurring influenza.201323552014
progressive emergence of an oseltamivir-resistant a(h3n2) virus over two courses of oseltamivir treatment in an immunocompromised paediatric patient.a minor viral population of oseltamivir-resistant a(h3n2) viruses (e119v neuraminidase mutation) was selected and maintained in a continually infected immunocompromised child following initial oseltamivir treatment. a subsequent course of oseltamivir given 7 weeks later rapidly selected for the e119v variant resulting in a near-pure population of the resistant virus. the study highlights the challenges of oseltamivir treatment of immunocompromised patients that are continually shedding virus and ...201323551973
prior infection of pigs with a recent human h3n2 influenza virus confers minimal cross-protection against a european swine h3n2 virus.h3n2 influenza viruses circulating in humans and european pigs originate from the pandemic a/hong kong/68 virus. because of slower antigenic drift in swine, the antigenic divergence between swine and human viruses has been increasing. it remains unknown to what extent this results in a reduced cross-protection between recent human and swine h3n2 influenza viruses.201323551882
m2e-displaying virus-like particles with associated rna promote t helper 1 type adaptive immunity against influenza a.the ectodomain of influenza a matrix protein 2 (m2e) is a candidate for a universal influenza a vaccine. we used recombinant hepatitis b core antigen to produce virus-like particles presenting m2e (m2e-vlps). we produced the vlps with and without entrapped nucleic acids and compared their immunogenicity and protective efficacy. immunization of balb/c mice with m2e-vlps containing nucleic acids induced a stronger, th1-biased antibody response compared to particles lacking nucleic acids. the forme ...201323527091
complete genome sequence of a canine-origin h3n2 feline influenza virus isolated from domestic cats in south korea.a canine-origin korean h3n2 feline influenza virus (fiv), a/feline/korea/01/2010 (h3n2), was isolated in 2010 from a dead cat with severe respiratory disease. here, we report the first complete genome sequence of this virus, containing 3' and 5' noncoding regions, which will help elucidate the molecular basis of the pathogenesis, transmission, and evolution of fiv.201323516235
experimental infection of dogs with h3n2 canine influenza virus from china.canine influenza virus (civ) is an emerging pathogen that causes acute respiratory disease in dogs. the aim of this study was to investigate the pathogenicity of a/canine/jiangsu/06/2010 (h3n2) virus isolated in china. nine dogs were inoculated intranasally with 107.95 of 50% egg infectious dose (eid50) of the virus. the onset of clinical signs and virus shedding was observed on day 1 post-infection (p.i.). the peak clinical score occurred between days 4 and 6 p.i. the experimentally infected do ...201323510585
serologic reports of h3n2 canine influenza virus infection in dogs in northeast china.reports of dogs with h3n2 canine influenza virus (civ) have been documented frequently. to better understand the seroprevalence of h3n2 civ among dogs in northeast china, here we report for the first time a relatively high seroprevalence of h3n2 civ infection in dogs in northeast china. forty-five of the 223 canine sera (20.2%) and 166 of the 500 canine sera (33.2%) tested feral dogs and pet dogs were seropositive by np-elisa, which is higher than that in southern china. the relative data provid ...201323503165
anti-influenza active and low toxic n-phenyl-substituted β-amidoamidines structurally related to natural antibiotic amidinomycin.a set of racemic n-phenyl-substituted β-amidoamidines hydrochlorides 4, which are structurally related to natural antiviral agent amidinomycin (1), was synthesized in four steps starting from methacryloyl anilide (5). in the final step of the synthetic route, an uncommon monoacylation of β-aminoamidine 8 at the less reactive β-phenylamino-group took place. to rationalize this result, a mechanism which involves initial acylation at the more active amidine-function followed by intramolecular acyl- ...201323489622
the influence of influenza virus infections on the development of tuberculosis.recently, it was shown that interferon-γ mediated immune responses, which play a major role in the control of infection with mycobacterium tuberculosis (mtb), can be inhibited by type i interferons. since type i interferons are abundantly induced during viral infections, we hypothesized that infections with influenza viruses might play a role in the development of active tb disease either directly after exposure to mtb or through reactivation of latent mtb infection. to explore this hypothesis w ...201323474302
the source of the pb1 gene in influenza vaccine reassortants selectively alters the hemagglutinin content of the resulting seed virus.the yields of egg-grown influenza vaccines are maximized by the production of a seed strain using a reassortment of the seasonal influenza virus isolate with a highly egg-adapted strain. the seed virus is selected based on high yields of viral hemagglutinin (ha) and expression of the surface antigens from the seasonal isolate. the remaining proteins are usually derived from the high-growth parent. however, a retrospective analysis of vaccine seeds revealed that the seasonal pb1 gene was selected ...201323468502
genetic characterization of avian-origin h3n2 canine influenza viruses isolated from guangdong during 2006-2012.canine influenza virus (civ) is an emerging pathogen that causes severe and acute respiratory disease in dogs. in 2006, the h3n2 canine influenza virus was first identified in dogs from guangdong province in china. up to now, nine civs have been isolated from different populations in guangdong. the nine isolates were grouped together with the canine h3n2 viruses isolated from dogs and felines in korea, when the eight phylogenetic trees constructed were compared. these findings emphasize the impo ...201323463173
highly pathogenic h5n1 influenza a virus strains provoke heterogeneous ifn-α/β responses that distinctively affect viral propagation in human cells.the fatal transmissions of highly pathogenic avian influenza a viruses (iav) of the h5n1 subtype to humans and high titer replication in the respiratory tract indicate that these pathogens can overcome the bird-to-human species barrier. while type i interferons (ifn-α/β) are well described to contribute to the species barrier of many zoonotic viruses, current data to the role of these antiviral cytokines during human h5n1 iav infections is limited and contradictory. we hypothesized an important ...201323451066
a polyphenol-rich extract from chaenomeles sinensis (chinese quince) inhibits influenza a virus infection by preventing primary transcription in vitro.the fruits of chaenomeles sinensis koehne (chinese quince) are distributed throughout china and japan. it has traditionally been known to have a therapeutic effect against respiratory symptoms caused by infectious diseases.201323439031
live attenuated seasonal and pandemic influenza vaccine in school-age children: a randomized controlled trial.the novel influenza a(h1n1pdm09) virus emerged in north america in early 2009 and rapidly spread worldwide. in this study we report the efficacy of the live attenuated monovalent h1n1pdm09 vaccine and 2009-10 seasonal influenza vaccine in a randomized double-blind placebo-controlled trial.201323434387
interim adjusted estimates of seasonal influenza vaccine effectiveness - united states, february 2013.early influenza activity during the 2012-13 season enabled estimation of the unadjusted effectiveness of the seasonal influenza vaccine. this report presents updated adjusted estimates based on 2,697 children and adults enrolled in the u.s. influenza vaccine effectiveness (flu ve) network during december 3, 2012-january 19, 2013. during this period, overall vaccine effectiveness (ve) (adjusted for age, site, race/ethnicity, self-rated health, and days from illness onset to enrollment) against in ...201323425960
kinetics of viral replication and induction of host responses in ferrets differs between ocular and intranasal routes of inoculation.while influenza viruses are typically considered respiratory pathogens, the ocular system represents a secondary entry point for virus to establish a productive respiratory infection and the location for rare instances of virus-induced conjunctivitis. we used the ferret model to conduct a side-by-side comparison of virus infectivity, kinetics of viral replication, and induction of host responses following inoculation by either the intranasal or ocular routes with two viruses, a/netherlands/230/0 ...201323415392
low vaccine effectiveness against influenza a(h3n2) virus among elderly people in denmark in 2012/13--a rapid epidemiological and virological assessment.in denmark, the 2012/13 influenza season has been dominated by influenza a(h3n2). we estimated the vaccine effectiveness (ve) of the trivalent influenza vaccine by linking national registers in a test-negative case-control study of patients tested for influenza aged ≥65 years. the adjusted ve against laboratory-confirmed influenza a and b was -11% (95% ci: -41 to 14) and 69% (95% ci: 26 to 87), respectively. genetic characterisation of the influenza a(h3n2) viruses indicated genetic drift, with ...201323410258
h3n2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice.broadly neutralizing antibodies directed against the conserved stalk domain of the viral hemagglutinin have attracted increasing attention in recent years. however, only a limited number of stalk antibodies directed against group 2 influenza hemagglutinins have been isolated so far. also, little is known about the general level of induction of these antibodies by influenza virus vaccination or infection. to characterize the anti-stalk humoral response in the mouse model as well as in humans, chi ...201323408625
detection of positive selection eliminating effects of structural constraints in hemagglutinin of h3n2 human influenza a virus.in the evolutionary studies of proteins, the average effect of natural selection operating on amino acid mutations may be examined by comparing the numbers of synonymous (ds) and nonsynonymous (dn) substitutions that have accumulated during the same time period. in this method, destabilizing mutations occurring across protein molecules may interfere with detection of natural selection, particularly positive selection, operating on other mutations. here an attempt to detect positive selection eli ...201323403095
interim estimates of influenza vaccine effectiveness in 2012/13 from canada's sentinel surveillance network, january 2013.the 2012/13 influenza season in canada has been characterised to date by early and moderately severe activity, dominated (90%) by the a(h3n2) subtype. vaccine effectiveness (ve) was assessed in january 2013 by canada's sentinel surveillance network using a test-negative case-control design. interim adjusted-ve against medically attended laboratory-confirmed influenza a(h3n2) infection was 45% (95% ci: 13-66). influenza a(h3n2) viruses in canada are similar to the vaccine, based on haemagglutinat ...201323399422
short communication: isolation and phylogenetic analysis of an avian-origin h3n2 canine influenza virus in dog shelter, china.a h3n2 canine influenza virus, a/canine/guangdong/3/2011 (h3n2), was isolated from roaming dogs in rural china. sequence and phylogenetic analysis of eight gene segments revealed that the a/canine/guangdong/3/2011 (h3n2) was most similar to a recent h3n2 canine influenza virus isolated in cats from south korea, which originated from an avian strain. to our knowledge, this is the first report of an avian-origin h3n2 civ which was isolated from roaming dogs in china. the epidemiologic information ...201323355070
experimental infection and natural contact exposure of ferrets with canine influenza virus (h3n2).epidemics of h3n2 canine influenza virus (civ) among dogs in south korea and southern china have raised concern over the potential for zoonotic transmission of these viruses. here, we analysed the pathogenesis and transmissibility of h3n2 civ in ferret. h3n2 civ replicated efficiently in the respiratory system of inoculated ferrets and caused acute necrotizing bronchioalveolitis and non-suppurative encephalitis. transmission of h3n2 civ was detected in three of six ferrets co-housed with inocula ...201323329681
the roles of competition and mutation in shaping antigenic and genetic diversity in influenza.influenza a (h3n2) offers a well-studied, yet not fully understood, disease in terms of the interactions between pathogen population dynamics, epidemiology and genetics. a major open question is why the virus population is globally dominated by a single and very recently diverged (2-8 years) lineage. classically, this has been modeled by limiting the generation of new successful antigenic variants, such that only a small subset of progeny acquire the necessary mutations to evade host immunity. a ...201323300455
influenza epidemiology in italy two years after the 2009-2010 pandemic: need to improve vaccination coverage.since 2000, a sentinel surveillance of influenza, influnet, exists in italy. it is coordinated by the ministry of health and is divided into two parts; one of these is coordinated by the national institute of health (nih), the other by the inter-university centre for research on influenza and other transmissible infections (ciri-it). the influenza surveillance system performs its activity from the 42nd week of each year (mid-october) to the 17th week of the following year (late april). only duri ...201323292210
h3n2 homeopathic influenza virus solution modifies cellular and biochemical aspects of mdck and j774g8 cell lines.influenza viruses cause highly contagious acute respiratory illnesses with significant mortality, especially among young children, elderly people, and individuals with serious medical conditions. this encourages the development of new treatments for human flu. biotherapies are diluted solutions prepared from biological products compounded following homeopathic procedures.201323290877
[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
avian-origin h3n2 canine influenza virus circulating in farmed dogs in guangdong, china.since 2006, more and more cases of the infectious h3n2 canine influenza virus (civ) in pet dogs have been reported in southern china. however, little is known about the prevalence situation of h3n2 civ infections in farmed dogs in china. this is the first systematic epidemiological surveillance of civ in different dog populations in southern china. two virus strains a/canine/guangdong/1/2011(h3n2) and a/canine/guangdong/5/2011(h3n2) were isolated from canine nasal swabs collected at one dog farm ...201323261544
retraction. triple reassortant swine influenza a (h3n2) virus in waterfowl. 201323260489
predictability of antigenic evolution for h3n2 human influenza a virus.influenza a virus continues to pose a threat to public health. since this virus can evolve escape mutants rapidly, it is desirable to predict the antigenic evolution for developing effective vaccines. although empirical methods have been proposed and reported to predict the antigenic evolution more or less accurately, they did not provide much insight into the effects of unobserved mutations and the mechanisms of antigenic evolution. here a theoretical method was introduced to predict the antige ...201324463525
h3n2 canine influenza virus causes severe morbidity in dogs with induction of genes related to inflammation and apoptosis.dogs are companion animals that live in close proximity with humans. canine h3n2 influenza virus has been isolated from pet dogs that showed severe respiratory signs and other clinical symptoms such as fever, reduced body weight, and interstitial pneumonia. the canine h3n2 influenza virus can be highly transmissible among dogs via aerosols. when we analyzed global gene expression in the lungs of infected dogs, the genes associated with the immune response and cell death were greatly elevated. ta ...201324090140
impact of prior seasonal h3n2 influenza vaccination or infection on protection and transmission of emerging variants of influenza a(h3n2)v virus in ferrets.influenza h3n2 a viruses continue to circulate in swine and occasionally infect humans, resulting in outbreaks of variant influenza h3n2 [a(h3n2)v] virus. it has been previously demonstrated in ferrets that a(h3n2)v viruses transmit as efficiently as seasonal influenza viruses, raising concern over the pandemic potential of these viruses. however, a(h3n2)v viruses have not acquired the ability to transmit efficiently among humans, which may be due in part to existing cross-reactive immunity to a ...201324089569
emergence of an oseltamivir-resistant influenza a/h3n2 virus in an elderly patient receiving a suboptimal dose of antiviral prophylaxis.we report the emergence of an influenza virus a/h3n2-e119v neuraminidase variant from an elderly patient with renal dysfunction who received a suboptimal dose of oseltamivir prophylaxis. in neuraminidase inhibition assays, the e119v variant showed a 413-fold increase in the 50% inhibitory oseltamivir concentration and grew at titers comparable to those of the wild type in vitro.201324088848
cell culture-selected substitutions in influenza a(h3n2) neuraminidase affect drug susceptibility assessment.assessment of drug susceptibility has become an integral part of influenza virus surveillance. in this study, we describe the drug resistance profile of influenza a(h3n2) virus, a/mississippi/05/2011, collected from a patient treated with oseltamivir and detected via surveillance. an mdck cell-grown isolate of this virus exhibited highly reduced inhibition by the neuraminidase (na) inhibitors (nais) oseltamivir (8,005-fold), zanamivir (813-fold), peramivir (116-fold), and laninamivir (257-fold) ...201324080660
mutation from arginine to lysine at the position 189 of hemagglutinin contributes to the antigenic drift in h3n2 swine influenza viruses.two distinct antigenic clusters were previously identified among the h3n2 swine influenza a viruses (iavs) and were designated h3n2siv-alpha and h3n2siv-beta (feng et al., 2013. journal of virology 87 (13), 7655-7667). a consistent mutation was observed at the position 189 of hemagglutinin (r189k) between h3n2siv-alpha and h3n2siv-beta fair isolates. to evaluate the contribution of r189k mutation to the antigenic drift from h3n2siv-alpha to h3n2siv-beta, four reassortant viruses with 189r or 189 ...201324074585
editorial commentary: variant influenza a(h3n2) virus: looking through a glass, darkly. 201324065323
outbreak of variant influenza a(h3n2) virus in the united states.variant influenza virus infections are rare but may have pandemic potential if person-to-person transmission is efficient. we describe the epidemiology of a multistate outbreak of an influenza a(h3n2) variant virus (h3n2v) first identified in 2011.201324065322
glyconanoparticles for the plasmonic detection and discrimination between human and avian influenza virus.a plasmonic bioassay for the specific detection of human influenza virus has been developed based on gold nanoparticles functionalised with a designed and synthesised thiolated trivalent α2,6-thio-linked sialic acid derivative. the glyconanoparticles consist of the thiolated trivalent α2,6-thio-linked sialic acid derivative and a thiolated polyethylene glycol (peg) derivative self-assembled onto the gold surface. varying ratios of the trivalent α2,6-thio-linked sialic acid ligand and the peg lig ...201324057694
effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011-2012 season in spain, among population targeted for vaccination.in spain, the influenza vaccine effectiveness (ve) was estimated in the last three seasons using the observational study cyceva conducted in the frame of the existing spanish influenza sentinel surveillance system. the objective of the study was to estimate influenza vaccine effectiveness (ve) against medically attended, laboratory-confirmed influenza-like illness (ili) among the target groups for vaccination in spain in the 2011-2012 season. we also studied influenza ve in the early (weeks 52/2 ...201324053661
dynamically correlated mutations drive human influenza a evolution.human influenza a virus undergoes recurrent changes in the hemagglutinin (ha) surface protein, primarily involved in the human antibody recognition. relevant antigenic changes, enabling the virus to evade host immune response, have been recognized to occur in parallel to multiple mutations at antigenic sites in ha. yet, the role of correlated mutations (epistasis) in driving the molecular evolution of the virus still represents a challenging puzzle. further, though circulation at a global geogra ...201324048220
critical role of segment-specific packaging signals in genetic reassortment of influenza a viruses.the fragmented nature of the influenza a genome allows the exchange of gene segments when two or more influenza viruses infect the same cell, but little is known about the rules underlying this process. here, we studied genetic reassortment between the a/moscow/10/99 (h3n2, mo) virus originally isolated from human and the avian a/finch/england/2051/91 (h5n2, en) virus and found that this process is strongly biased. importantly, the avian ha segment never entered the mo genetic background alone b ...201324043788
mutation tryptophan to leucine at position 222 of haemagglutinin could facilitate h3n2 influenza a virus infection in dogs.an avian-like h3n2 influenza a virus (iav) has recently caused sporadic canine influenza outbreaks in china and korea, but the molecular mechanisms involved in the interspecies transmission of h3n2 iav from avian to canine species are not well understood. sequence analysis showed that residue 222 in haemagglutinin (ha) is predominantly tryptophan (w) in the closely related avian h3n2 iav, but was leucine (l) in canine h3n2 iav. in this study, reassortant viruses rh3n2-222l (canine-like) and rh3n ...201323994833
design, synthesis and antiviral activity studies of schizonepetin derivatives.a series of schizonepetin derivatives have been designed and synthesized in order to obtain potent antivirus agents. the antiviral activity against hsv-1 and influenza virus h3n2 as well as the cytotoxicity of these derivatives was evaluated by using cytopathic effect (cpe) inhibition assay in vitro. compounds m2, m4, m5 and m34 showed higher inhibitory activity against hsv-1 virus with the tc50 values being in micromole. compounds m28, m33, and m35 showed higher inhibitory activity against infl ...201323965980
[development of a real-time reverse transcriptase pcr assay for detection of e119v amino acid change in neuraminidase of influenza a (h3n2) using the taqman-mgb probe].to develop a rapid duplex real-time reverse transcription pcr (rrt-pcr) method to detect e119v mutation on neuraminidase (na) of influenza a(h3n2) subtype with drug resistance to oseltamivir.201323958130
seasonal h3n2 influenza a virus fails to enhance staphylococcus aureus co-infection in a non-human primate respiratory tract infection model.staphylococcus aureus community-acquired pneumonia is often associated with influenza or an influenza-like syndrome. morbidity and mortality due to methicillin-resistant s. aureus (mrsa) or influenza and pneumonia, which includes bacterial co-infection, are among the top causes of death by infectious diseases in the united states. we developed a non-lethal influenza a virus (iav) (h3n2)/s. aureus co-infection model in cynomolgus macaques (macaca fascicularis) to test the hypothesis that seasonal ...201324104465
the kinase mtor modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus.highly pathogenic avian influenza viruses pose a continuing global threat. current vaccines will not protect against newly evolved pandemic viruses. the creation of 'universal' vaccines has been unsuccessful because the immunological mechanisms that promote heterosubtypic immunity are incompletely defined. we found here that rapamycin, an immunosuppressive drug that inhibits the kinase mtor, promoted cross-strain protection against lethal infection with influenza virus of various subtypes when a ...201324141387
longitudinal analysis of leukocyte differentials in peripheral blood of patients with acute respiratory viral infections.leukocyte counts and differentials are commonly acquired in patients with suspected respiratory viral infections and may contribute diagnostic information. however, most published work is limited to a single timepoint at initial presentation to a medical provider, which may correspond to widely varying points in the course of disease.201324140015
efficacy of a levulinic acid plus sodium dodecyl sulfate (sds)-based sanitizer on inactivation of influenza a virus on eggshells.influenza a virus poses a major public health concern and is associated with annual epidemics and occasional pandemics. influenza a h3n2 viruses, which are an important cause of human influenza, can infect birds and mammals. contaminated undercooked poultry products including eggs with avian influenza virus constitute a possible risk of transmission to humans. in this study, a novel levulinic acid plus sodium dodecyl sulfate (sds) sanitizer was evaluated for eggshell decontamination. influenza a ...201324132876
epidemiology of seasonal influenza in bangkok between 2009 and 2012.this study investigated influenza activity in bangkok, thailand between june 2009 and july 2012.201324129626
subcellular proteomic analysis of human host cells infected with h3n2 swine influenza virus.cross-species transmissions of swine influenza viruses (sivs) raise great public health concerns. in this study, subcellular proteomic profiles of human a549 cells inoculated with h3n2 subtype siv were used to characterize dynamic cellular responses to infection. by 2de and ms, 27 differentially expressed (13 upregulated, 14 downregulated) cytoplasmic proteins and 20 differentially expressed (13 upregulated, 7 downregulated) nuclear proteins were identified. gene ontology analysis suggested that ...201324115376
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