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infectivity phenotypes of h3n2 influenza a viruses in primary swine respiratory epithelial cells are controlled by sialic acid binding.in the late 1990s, triple reassortant h3n2 influenza a viruses emerged and spread widely in the us swine population. we have shown previously that an isolate representative of this virus-lineage, a/swine/minnesota/593/99 (sw/mn), exhibits phenotypic differences compared to a wholly human-lineage h3n2 virus isolated during the same time period, a/swine/ontario/00130/97 (sw/ont). specifically, sw/mn was more infectious for pigs and infected a significantly higher proportion of cultured primary swi ...201222353399
antiviral activity of polyporoid mushrooms (higher basidiomycetes) from altai mountains (russia).antiviral activity against type a influenza virus of birds a/chicken/kurgan/05/2005 (h5n1) and humans a/aichi/2/68 (h3n2) was investigated for aqueous extracts from mycelium of 11 basidial fungi species collected in the altai mountains (altai republic, russia). the most perspective strains for producing antiviral medicines are studied strains daedaleopsis confragosa, datronia mollis, ischnoderma benzoinum, trametes gibbosa, t. versicolor, laricifomes officinalis, and lenzites betulina.201222339706
induction of a cross-reactive antibody response to influenza virus m2 antigen in pigs by using a sendai virus vector.protecting pigs from simultaneous infection with avian, swine, and human influenza viruses would be an effective strategy to prevent the emergence of reassortants with pandemic potential. m2 protein is a candidate antigen for so-called 'universal vaccines,' which confer cross-protection to different influenza viruses in a strain- and subtype-independent manner. we tested whether a recombinant f gene-deleted sendai virus vector that contained an m2 gene derived from an h5n1 avian influenza virus ...201222336036
reactivity of human convalescent sera with influenza virus hemagglutinin protein mutants at antigenic site a.how the antibodies of individual convalescent human sera bind to each amino acid residue at the antigenic sites of hemagglutinin (ha) of influenza viruses, and how the antigenic drift strains of influenza viruses are selected by human sera, is not well understood. in our previous study, it was found by a binding assay with a chimeric ha between a/kamata/14/91 (ka/91) and a/aichi/2/68 that convalescent human sera, following ka/91 like (h3n2) virus infection, bind to antigenic site a of ka/91 ha. ...201222309642
invasive pneumococcal pneumonia and respiratory virus co-infections.to confirm whether respiratory virus infections increase susceptibility to invasive pneumococcal pneumonia, we examined data from 11 influenza seasons (1994-2005) in the united states. invasive pneumococcal pneumonia was significantly associated with influenza and respiratory syncytial virus activities in 5 seasons. association strength was higher when strain h3n2 was the predominant influenza a virus strain.201222305270
cross-reactive antibody to swine influenza a(h3n2) subtype virus in children and adults before and after immunisation with 2010/11 trivalent inactivated influenza vaccine in canada, august to november 2010.in pre- and post-immunisation sera from children (17-120 months-old) and adults (20-59 years-old) immunised with 2010/11 trivalent inactivated influenza vaccine, we assessed age-related patterns of sero-susceptibility and vaccine-induced cross-reactive antibodies to a representative swine h3n2 (swh3n2) and a related ancestral human h3n2 (a/sydney/5/1997) influenza virus. few children but a greater proportion of adults showed pre-immunisation haemagglutination inhibition titres ≥40 to either viru ...201222297136
synthesis and preliminary biologic evaluation of 5-substituted-2-(4-substituted phenyl)-1,3-benzoxazoles as a novel class of influenza virus a inhibitors.the diversity-oriented chemistry synthesis together with the random screening approach has permitted the discovery and optimization of novel antiviral lead compounds. in this paper, a series of novel 5-substituted-2-(4-substituted phenyl)-1,3-benzoxazoles was synthesized and evaluated for their in vitro anti-influenza a virus and anti-influenza b virus activity. the activity was monitored by the mts assay in the madin-darby canine kidney cells. compound 7h showed excellent inhibitory activity an ...201222284752
evidence for n-glycan shielding of antigenic sites during evolution of human influenza a virus hemagglutinin.after the emergence of influenza a viruses in the human population, the number of n-glycosylation sites (ngs) in the globular head region of hemagglutinin (ha) has increased continuously for several decades. it has been speculated that the addition of ngs to the globular head region of ha has conferred selective advantages to the virus by preventing the binding of antibodies (ab) to antigenic sites (as). here, the effect of n-glycosylation on the binding of ab to as in human influenza a virus su ...201222258255
influenza virus a infection of human monocyte and macrophage subpopulations reveals increased susceptibility associated with cell differentiation.influenza virus infection accounts for significant morbidity and mortality world-wide. interactions of the virus with host cells, particularly those of the macrophage lineage, are thought to contribute to various pathological changes associated with poor patient outcome. development of new strategies to treat disease therefore requires a detailed understanding of the impact of virus infection upon cellular responses. here we report that human blood-derived monocytes could be readily infected wit ...201222238612
evolution of the receptor binding properties of the influenza a(h3n2) hemagglutinin.the hemagglutinin (ha) of influenza a(h3n2) virus responsible for the 1968 influenza pandemic derived from an avian virus. on introduction into humans, its receptor binding properties had changed from a preference for avian receptors (α2,3-linked sialic acid) to a preference for human receptors (α2,6-linked sialic acid). by 2001, the avidity of human h3 viruses for avian receptors had declined, and since then the affinity for human receptors has also decreased significantly. these changes in rec ...201223236176
resolution of immune response by recombinant transforming growth factor-beta (rtgf-β) during influenza a virus infection.replication of influenza a virus in the respiratory tract leads to cell damage and liberation of cytokines and chemokines. the in vivo cytokine induction and modulation by recombinant transforming growth factor- β1 (rtgf-β1) has not been studied. therefore, in the present study the effect of rtgf-β1, a potent immunomodulatory cytokine which has anti-inflammatory properties and downregulates the release of inflammatory molecules, against influenza-virus infection in the airway of mice was investi ...201223168705
differential interactions of virulent and non-virulent h. parasuis strains with naïve or swine influenza virus pre-infected dendritic cells.pigs possess a microbiota in the upper respiratory tract that includes haemophilus parasuis. pigs are also considered the reservoir of influenza viruses and infection with this virus commonly results in increased impact of bacterial infections, including those by h. parasuis. however, the mechanisms involved in host innate responses towards h. parasuis and their implications in a co-infection with influenza virus are unknown. therefore, the ability of a non-virulent h. parasuis serovar 3 (sw114) ...201223157617
enantiomers of an indole alkaloid containing unusual dihydrothiopyran and 1,2,4-thiadiazole rings from the root of isatis indigotica.a pair of enantiomers (1a and 1b) of an indole alkaloid containing dihydrothiopyran and 1,2,4-thiadiazole rings was isolated from an aqueous extract of the root of isatis indigotica. the structures and absolute configurations of the enantiomers were determined by extensive spectroscopic analysis, especially 2d nmr, modified mosher's method, and electronic cd (ecd). the proposed biosynthetic pathway and preliminary investigations of the biological activity of compounds 1a and 1b against influenza ...201223131196
mutations to a/puerto rico/8/34 pb1 gene improves seasonal reassortant influenza a virus growth kinetics.it is desirable for influenza vaccine virus strains to have phenotypes that include good growth and hemagglutinin (ha) protein yield. the quality of these characteristics varies among the vaccine viruses and is usually due to multigenic effects. many influenza a virus vaccine viruses are made as reassortants of the high yield virus a/puerto rico/8/34 (pr/8) and a circulating seasonal virus. co-infection of eggs with the two viruses, and selection of reassortants with the ha and neuraminidase (na ...201223116694
high-performance method for specific effect on nucleic acids in cells using tio2~dna nanocomposites.nanoparticles are used to solve the current drug delivery problem. we present a high-performance method for efficient and selective action on nucleic acid target in cells using unique tio(2)·pl-dna nanocomposites (polylysine-containing dna fragments noncovalently immobilized onto tio(2) nanoparticles capable of transferring dna). these nanocomposites were used for inhibition of human influenza a (h3n2) virus replication in infected mdck cells. they showed a low toxicity (tc(50) ≈ 1800 μg/ml) and ...201223091696
distribution of surface glycoproteins on influenza a virus determined by electron cryotomography.we use electron cryotomography to reconstruct virions of two influenza a h3n2 virus strains. the maps reveal the structure of the viral envelope containing hemagglutinin (ha) and neuraminidase (na) glycoproteins and the virus interior containing a matrix layer and an assembly of ribonucleoprotein particles (rnps) that package the genome. we build a structural model for the viral surface by locating copies of the x-ray structure of the ha ectodomain into density peaks on the virus surface. we cal ...201223063838
interaction network linking the human h3n2 influenza a virus genomic rna segments.the genome of influenza a viruses is comprised of eight negative-sense viral rnas (vrnas) that form viral ribonucleoproteins (vrnps). in order to be infectious, an influenza a viral particle must encapsidate at least one copy of each of the vrnas. thus, even though genome segmentation is evolutionary advantageous, it undeniably complicates viral assembly, which is believed to occur through a selective mechanism that still remains to be understood. using electron tomography 3d-reconstructions, we ...201223063835
complete genome sequence of an h3n2 avian influenza virus isolated from a live poultry market in eastern china.previous studies indicate that the h3 influenza virus has the ability to establish infection upon interspecies transmission and poses a threat to mammals. therefore, it is important to enhance the surveillance of h3 avian influenza viruses (aivs). in this study, a/duck/shanghai/c84/2009(h3n2) (c84) was isolated from a live poultry market in shanghai, china. using pcr and sequencing analyses, we obtained the whole-genome sequence of this virus. the h3n2 virus proved to be a novel multiple-gene re ...201223043175
influenza virus neuraminidases with reduced enzymatic activity that avidly bind sialic acid receptors.influenza virus neuraminidase (na) cleaves off sialic acid from cellular receptors of hemagglutinin (ha) to enable progeny escape from infected cells. however, na variants (d151g) of recent human h3n2 viruses have also been reported to bind receptors on red blood cells, but the nature of these receptors and the effect of the mutation on na activity were not established. here, we compare the functional and structural properties of a human h3n2 na from a/tanzania/205/2010 and its d151g mutant, whi ...201223015718
complete genome sequence of an h3n2 canine influenza virus from dogs in jiangsu, china.a canine influenza virus (civ) strain of avian origin designated a/canine/jiangsu/06/2010 (h3n2) was isolated from dogs exhibiting severe respiratory disease in jiangsu, china. we announce the complete genome sequence of this viral strain and report major findings from the genomic analysis. this sequence will help us understand the molecular characteristics and evolutionary of h3n2 civ in china.201222997421
[characterization of a nonspecific inhibitor found in human sera raised against the 2006/07 influenza vaccine strain a/hiroshima/52/2005 (h3n2) virus].the serology of influenza viruses typically uses hemagglutination inhibition (hi) or the neutralization test (nt). however, the sera of many humans and animals contain nonspecific inhibitors of hemagglutinin that must be inactivated or removed from the serum before use in the hi assay. any nonspecific inhibitor in human serum is typically inactivated by pre-treatment with receptor-destroying enzyme (rde). however, during the 2006/07 influenza circulating season, we observed that influenza vaccin ...201222991846
comparison of the cross-reactive anti-influenza neutralizing activity of polymeric and monomeric iga monoclonal antibodies.here we examined whether polymeric iga (piga) and monomeric iga (miga) antibodies differ in their ability to neutralize drift viruses within the same subtype. we used an iga monoclonal antibody (mab; h1-21) against influenza virus strain a/hiroshima/52/2005 (a/hiroshima; h3n2). the mab was obtained after immunizing mice mucosally with a split-virion (sv) vaccine. the mab contained both miga and piga forms. it reacted with the homologous virus and cross-reacted with drift viruses a/new york/55/20 ...201222985289
[molecular evolution of human influenza h3n2 virus hemagglutinin genes in guangdong china].the molecular characterization and phylogenetic analysis of hemagglutinin (ha) genes of human influenza h3n2 viruses in guangdong, china from 2007 to 2010 were studied in this study. by space-time sampling of strains, the ha genes of h3n2 strains from guangdong were sequenced and searched from internet, and then the variation and evolution of ha genes were conducted by lasergene 7.1 and mega 5.05 and evolutionary rates were analyzed by epidemiological data. the phylogenetic tree was established ...201222978155
evidence of h3n2 canine influenza virus infection before 2007. 201222952134
h3n2 flu virus infections increase during fair season. 201222948682
complete genome sequence of an avian-origin h3n2 canine influenza a virus isolated in farmed dogs in southern china.we report here the complete genomic sequence of an avian-origin h3n2 canine influenza a virus containing multiple mutations in farmed dogs in southern china. phylogenetic analyses of the sequences of all eight viral rna segments demonstrated that these are wholly avian influenza viruses of the asia lineage. to our knowledge, this is the first report of interspecies transmission of an avian h3n2 influenza virus to domestic farm dogs under natural conditions in southern china. the amino acid infor ...201222923798
molecular genetic analysis of influenza a/h3n2 virus strains isolated in western siberia in the 2010-2011 epidemic season.molecular genetic and antigenic features of influenza a/h3n2 virus strains isolated in western siberia in 2011 are similar to those of the vaccine strain a/perth/16/2009 despite a number of unique amino-acid changes. the strains lack specific amino-acid changes in na protein providing decrease of sensibility to na inhibitors activity that used in medical practice. based on phylogenic analysis of ha protein amino-acid sequences examined strains are similar to influenza a/h3n2 virus strains circul ...201222922296
influenza a h3n2 subtype virus ns1 protein targets into the nucleus and binds primarily via its c-terminal nls2/nols to nucleolin and fibrillarin.influenza a virus non-structural protein 1 (ns1) is a virulence factor, which is targeted into the cell cytoplasm, nucleus and nucleolus. ns1 is a multi-functional protein that inhibits host cell pre-mrna processing and counteracts host cell antiviral responses. previously, we have shown that the ns1 protein of the h3n2 subtype influenza viruses possesses a c-terminal nuclear localization signal (nls) that also functions as a nucleolar localization signal (nols) and targets the protein into the ...201222909121
genome sequence of a novel reassortant h3n2 avian influenza virus in southern china.the distribution and prevalence of h3 subtype influenza viruses in avian and mammalian hosts constitutes a potential threat to both human and avian health. we report a complete genome sequence of a novel reassortant h3n2 avian influenza virus. phylogenetic analysis showed that ha and na showed the highest sequence homologies with those of a/white-backed munia/hong kong/4519/2009 (h3n2). however, the internal genes had the highest sequence homologies with those of h6 and h7 subtypes. the data pro ...201222879622
complete genome sequence of an avian-origin h3n2 canine influenza virus isolated from dogs in south korea.an avian-origin korean h3n2 canine influenza virus (civ) strain, designated a/canine/korea/01/2007 (h3n2), was isolated from nasal swabs of pet dogs exhibiting severe respiratory syndrome in 2007. in the present study, we report the first complete genome sequence containing 3' and 5' noncoding regions (ncrs) of h3n2 civ, which will provide important insights into the molecular basis of pathogenesis, transmission, and evolution of civ.201222879618
complete genome sequence of a novel avian-like h3n2 swine influenza virus discovered in southern china.we report here the complete genomic sequence of a novel avian-like h3n2 swine influenza virus containing an h5n1 highly pathogenic avian influenza virus segment that was obtained from swine in southern china. phylogenetic analysis indicated that this virus might originate from domestic aquatic birds. the sequence information provided herein suggests that continuing study is required to determine if this virus can be established in the swine population and pose potential threats to public health.201222879607
cross-reactive and vaccine-induced antibody to an emerging swine-origin variant of influenza a virus subtype h3n2 (h3n2v).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, primarily among children. we estimate levels of cross-reactive antibody to h3n2v by age and assess whether seasonal trivalent inactivated influenza vaccine (tiv), with or without adjuvant, may increase seroprotection.201222872731
clonal interference in the evolution of influenza.the seasonal influenza a virus undergoes rapid evolution to escape human immune response. adaptive changes occur primarily in antigenic epitopes, the antibody-binding domains of the viral hemagglutinin. this process involves recurrent selective sweeps, in which clusters of simultaneous nucleotide fixations in the hemagglutinin coding sequence are observed about every 4 years. here, we show that influenza a (h3n2) evolves by strong clonal interference. this mode of evolution is a red queen race b ...201222851649
immunodominance of antigenic site b over site a of hemagglutinin of recent h3n2 influenza viruses.h3n2 influenza viruses have now circulated in the human population for 43 years since the pandemic of 1968, accumulating sequence changes in the hemagglutinin (ha) and neuraminidase (na) that are believed to be predominantly due to selection for escape from antibodies. examination of mutations that persist and accumulate led to identification of antigenically significant mutations that are contained in five antigenic sites (a-e) mapped on to the h3 ha. in early h3n2 isolates, antigenic site a ap ...201222848649
molecular and microscopic analysis of bacteria and viruses in exhaled breath collected using a simple impaction and condensing method.exhaled breath condensate (ebc) is increasingly being used as a non-invasive method for disease diagnosis and environmental exposure assessment. by using hydrophobic surface, ice, and droplet scavenging, a simple impaction and condensing based collection method is reported here. human subjects were recruited to exhale toward the device for 1, 2, 3, and 4 min. the exhaled breath quickly formed into tiny droplets on the hydrophobic surface, which were subsequently scavenged into a 10 µl rolling de ...201222848436
evidence for antigenic seniority in influenza a (h3n2) antibody responses in southern china.a key observation about the human immune response to repeated exposure to influenza a is that the first strain infecting an individual apparently produces the strongest adaptive immune response. although antibody titers measure that response, the interpretation of titers to multiple strains--from the same sera--in terms of infection history is clouded by age effects, cross reactivity and immune waning. from july to september 2009, we collected serum samples from 151 residents of guangdong provin ...201222829765
phylogenetic, molecular and drug-sensitivity analysis of ha and na genes of human h3n2 influenza a viruses in guangdong, china, 2007-2011.annual h3n2 subtype influenza outbreaks in guangdong, china are a severe public health issue and require ongoing monitoring of emerging viral variants. the variation and evolution of haemagglutinin (ha) and neuraminidase (na) genes of influenza isolates from guangdong during 2007-2011 and others from genbank were analysed using lasergene 7.1 and mega 5.05, and serological analysis of antigens was determined by haemagglutination inhibition (hi). susceptibility to antiviral drugs was correlated wi ...201322827898
dietary abscisic acid ameliorates influenza-virus-associated disease and pulmonary immunopathology through a pparγ-dependent mechanism.the anti-inflammatory phytohormone abscisic acid (aba) modulates immune and inflammatory responses in mouse models of colitis and obesity. aba has been identified as a ligand of lanthionine synthetase c-like 2, a novel therapeutic target upstream of the peroxisome proliferator-activated receptor γ (pparγ) pathway. the goal of this study was to investigate the immune modulatory mechanisms underlying the anti-inflammatory efficacy of aba against influenza-associated pulmonary inflammation. wild-ty ...201322995385
glutathione peroxidase-1 reduces influenza a virus-induced lung inflammation.oxidative stress caused by excessive reactive oxygen species production is implicated in influenza a virus-induced lung disease. glutathione peroxidase (gpx)-1 is an antioxidant enzyme that may protect lungs from such damage. the objective of this study was to determine if gpx-1 protects the lung against influenza a virus-induced lung inflammation in vivo. male wild-type (wt) or gpx-1(-/-) mice were inoculated with hkx31 (h3n2, 1 × 10(4) plaque-forming units), and bronchoalveolar lavage fluid (b ...201323002098
identification and characterization of avian-origin h3n2 canine influenza viruses in northern china during 2009-2010.twelve avian-origin h3n2 influenza strains were isolated from dogs with signs of respiratory disease in northern china during 2009-2010. phylogenetic analysis showed that eight gene segments of all the isolates had a close relationship with those of avian-origin h3n2 canine influenza viruses (civs) from south korea and southern china. genetic analysis indicated that these isolates had a perqtr/g ha cleavage motif, which differed from the pekqtr/g motif of canine viruses before 2007. noteworthy, ...201323063406
neutralizing dna aptamers against swine influenza h3n2 viruses.triple reassortant influenza a viruses (iavs) of swine, particularly the north american h3n2 subtype, circulate in swine herds and may reassort and result in the emergence of novel zoonotic strains. current diagnostic tools rely on isolation of the viruses, followed by serotyping by hemagglutination or genome sequencing, both of which can be expensive and time-consuming. thus, novel subtype-specific ligands and methods are needed for rapid testing and subtyping of iavs in the field. to address t ...201323077124
seasonal trivalent inactivated influenza vaccine does not protect against newly emerging variants of influenza a (h3n2v) virus in ferrets.the recent increase in human cases of influenza a h3n2 variant virus [a(h3n2)v] highlights the need to assess whether seasonal influenza vaccination provides cross-protection against a(h3n2)v virus. our data demonstrate that the 2011-2012 trivalent inactivated influenza vaccine (tiv) protected ferrets against homologous h3n2 virus challenge but provided minimal to no protection against a(h3n2)v virus. the complete absence of specific hemagglutination inhibition antibody response to a(h3n2)v is c ...201323115290
characterization of an h3n2 canine influenza virus isolated from tibetan mastiffs in china.ten 3-month-old tibetan mastiffs became ill 2 days after they were bought from a tibetan mastiff exhibition, and 4 of them died 2 weeks later. a canine influenza virus (zj0110) was isolated from the lung of a deceased tibetan mastiff and was characterized in detail. sequence analysis indicated that the 8 genes of the canine isolate were most similar to those of avian-origin canine influenza viruses (h3n2) isolated in south korea in 2007, with which they shared >98% sequence identity. zj0110 coul ...201323107656
a "pre-seasonal" hospital outbreak of influenza pneumonia caused by the drift variant a/victoria/361/2011-like h3n2 viruses, hong kong, 2011.beginning from late 2011 and early 2012, increasing circulation of antigenically drifted influenza a/victoria/361/2011-like h3n2 viruses within genotype 3 of the a/victoria/208/2009 clade have been reported in multiple european countries and elsewhere. whether these emerging viruses are associated with increased disease severity is unclear.201323201458
neutrophils infected with highly virulent influenza h3n2 virus exhibit augmented early cell death and rapid induction of type i interferon signaling pathways.we developed a model of influenza virus infection of neutrophils by inducing differentiation of the mpro promyelocytic cell line. after 5 days of differentiation, about 20-30% of mature neutrophils could be detected. only a fraction of neutrophils were infected by highly virulent influenza (hvi) virus, but were unable to support active viral replication compared with mdck cells. hvi infection of neutrophils augmented early and late apoptosis as indicated by annexin v and tunel assays. comparison ...201323195410
genetic drift influenza a(h3n2) virus hemagglutinin (ha) variants originated during the last pandemic turn out to be predominant in the 2011-2012 season in northern italy.influenza a(h3n2) virus is once again the predominant strain after the 2009 pandemic. its molecular epidemiology and phylogeny were investigated during the 2011-2012 season in northern italy. the epidemiological and virological influenza surveillance was carried out within the framework of the italian influenza surveillance network. the hemagglutinin (ha) gene of the a(h3n2) viruses detected was analyzed by means of a time-scaled phylogenetic approach. in northern italy, the 2011-2012 epidemic w ...201323174527
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
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