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receptor binding and ph stability - how influenza a virus hemagglutinin affects host-specific virus infection.influenza a virus strains adopt different host specificities mainly depending on their hemagglutinin (ha) protein. via ha, the virus binds sialic acid receptors of the host cell and, upon endocytic uptake, ha triggers fusion between the viral envelope bilayer and the endosomal membrane by a low ph-induced conformational change leading to the release of the viral genome into the host cell cytoplasm. both functions are crucial for viral infection enabling the genesis of new progeny virus. adaptati ...201424161712
plc-γ1 signaling plays a subtype-specific role in postbinding cell entry of influenza a virus.host signaling pathways and cellular proteins play important roles in the influenza viral life cycle and can serve as antiviral targets. in this study, we report the engagement of host phosphoinositide-specific phospholipase γ1 (plc-γ1) in mediating cell entry of influenza virus h1n1 but not h3n2 subtype. both plc-γ1-specific inhibitor and short hairpin rna (shrna) strongly suppress the replication of h1n1 but not h3n2 viruses in cell culture, suggesting that plc-γ1 plays an important subtype-sp ...201424155396
activation of influenza a viruses by host proteases from swine airway epithelium.pigs are important natural hosts of influenza a viruses, and due to their susceptibility to swine, avian, and human viruses, they may serve as intermediate hosts supporting adaptation and genetic reassortment. cleavage of the influenza virus surface glycoprotein hemagglutinin (ha) by host cell proteases is essential for viral infectivity. most influenza viruses, including human and swine viruses, are activated at a monobasic ha cleavage site, and we previously identified tmprss2 and hat to be re ...201424155384
newly emerging mutations in the matrix genes of the human influenza a(h1n1)pdm09 and a(h3n2) viruses reduce the detection sensitivity of real-time reverse transcription-pcr.new variants of the influenza a(h1n1)pdm09 and a(h3n2) viruses were detected in taiwan between 2012 and 2013. some of these variants were not detected in clinical specimens using a common real-time reverse transcription-pcr (rt-pcr) assay that targeted the conserved regions of the viral matrix (m) genes. an analysis of the m gene sequences of the new variants revealed that several newly emerging mutations were located in the regions where the primers or probes of the real-time rt-pcr assay bind; ...201424153120
molecular epidemiology of influenza a virus infection in cyprus in four consecutive seasons (2009 pandemic-2013).the aim of this study was to investigate the epidemiology of influenza a virus infection in cyprus from the 2009 pandemic until 2013. pandemic influenza a(h1n1)2009 virus infections outnumbered infections with other respiratory viruses until the end of 2009. the pandemic virus was also the prevalent influenza strain during influenza season 2010-2011; however, it was completely replaced by h3n2 subtype in the next season. during the most recent influenza season, 2012-2013, the pandemic strain was ...201424152574
administration of as03b-adjuvanted a(h1n1)pdm09 vaccine in children aged <3 years enhances antibody response to h3 and b viruses following a single dose of trivalent vaccine one year later.we report on a follow-up clinical and serological investigation of 274 children who received seasonal influenza vaccine (trivalent inactivated vaccine [tiv]) 1 year after receipt of either as03(b)-adjuvanted subunit or whole virus monovalent a(h1n1)pdm09 vaccine and describe the antibody responses to the h3n2 a/perth/16/2009 and b/brisbane/60/2008 components of tiv.201424149079
review of 10 years of clinical experience with chinese domestic trivalent influenza vaccine anflu®.influenza viruses cause annual winter epidemics globally and influenza vaccination is most effective way to prevent the disease or severe outcomes from the illness, especially in developing countries. however, the majority of the world's total production capacity of influenza vaccine is concentrated in several large multinational manufacturers. a safe and effective preventive vaccine for the developing countries is urgent. anflu®, a chinese domestic preservative-free, split-virus trivalent influ ...201424104060
survival of influenza virus on human fingers.indirect transmission of the influenza virus via finger contamination with respiratory mucus droplets has been hypothesized to contribute to transmission in the community. under laboratory conditions, influenza-infected respiratory droplets were reconstituted as close as possible to natural conditions. we investigated experimentally the survival of influenza a (h3n2) and a (h1n1)pdm09 viruses on human fingers. infectious virus was easily recoverable on all fingers 1 min after fingertip contamina ...201423927722
mortality attributable to seasonal and pandemic influenza, australia, 2003 to 2009, using a novel time series smoothing approach.official statistics under-estimate influenza deaths. time series methods allow the estimation of influenza-attributable mortality. the methods often model background, non-influenza mortality using a cyclic, harmonic regression model based on the serfling approach. this approach assumes that the seasonal pattern of non-influenza mortality is the same each year, which may not always be accurate.201423755139
prevalence of antibodies to european porcine influenza viruses in humans living in high pig density areas of germany.the risk of zoonotic human infection caused by european porcine influenza virus strains was estimated in german regions with a high pig density. sera from 622 healthy volunteers were collected between april 2009 and november 2011, mainly in westphalia and western lower saxony. these included 362 subjects with occupational contact to pigs and 260 blood donors without any direct exposition to pigs. samples were analysed by the haemagglutination inhibition (hi) assay against a panel of six swine vi ...201424013183
first report of seroprevalence of swine influenza a virus in tibetan pigs in tibet, china.swine influenza a virus (siv) is zoonotic pathogen that can be acquired by food-borne transmission because food animals, for example pigs, are recognized as a reservoir. the objectives of this study were to determine the seroprevalence of anti-siv (h1n1 and h3n2) in tibetan pigs in tibet nationality autonomous region, china, a region with cold weather and high altitude. a total of 421 serum samples were randomly collected from tibetan pigs in tibet and were evaluated for antibodies against siv u ...201423955014
antivirally active ribavirin analogues--4,5-disubstituted 1,2,3-triazole nucleosides: biological evaluation against certain respiratory viruses and computational modelling.ribavirin is a broad-spectrum antiviral agent that derives some of its activity from inhibition of cellular inosine monophosphate dehydrogenase (impdh), resulting in lower guanosine triphosphate (gtp) levels. here we report the biological activities of three ribavirin analogues.201423538746
surveillance of human influenza a(h3n2) virus from 1999 to 2009 in southern italy.the aim of this study was to evaluate the presence of influenza virus co-infections in humans and changes in the genetic variability of a(h3n2) virus strains in southern italy from 1999 to 2009. a partial sequence of the haemagglutinin (ha) gene by human influenza h3n2 strains identified in oropharyngeal swabs from patients with influenza-like illness was analysed by dna sequencing and a phylogenetic analysis was performed. during the seasons 1999-2000, 2002-2003, 2004-2005 and 2008-2009, the in ...201423967903
molecular characterization and phylogenetic analysis of h3 subtype avian influenza viruses isolated from domestic ducks in zhejiang province in china.in 2013, 15 avian influenza viruses (aivs), h3n2 (n = 7), h3n3 (n = 3), h3n6 (n = 3), and h3n8 (n = 2), were isolated from domestic ducks in zhejiang province in china. these strains were characterized by whole genome sequencing with subsequent phylogenetic analysis and genetic comparison. phylogenetic analysis of all eight viral genes showed that these strains clustered in the aiv eurasian lineage. analysis of the neuraminidase (na) gene indicates that a re-assortment event between h3 and h9n2 ...201424748106
treatment of influenza virus with beta-propiolactone alters viral membrane fusion.beta-propiolactone (bpl) is commonly used as an inactivating reagent to produce viral vaccines. although bpl has been described to chemically modify nucleic acids, its effect on viral proteins, potentially affecting viral infectivity, remains poorly studied. here, a h3n2 strain of influenza virus was submitted to treatment with various bpl concentrations (2-1000μm). cell infectivity was progressively reduced and entirely abolished at 1mm bpl. virus fusion with endosome being a critical step in v ...201424140008
viral etiology of influenza-like illnesses during the influenza season between december 2011 and april 2012.the aim of this study was to determine the frequency of respiratory viruses responsible for respiratory tract infections in turkish children during the 2011-2012 influenza season. nasal swabs were obtained from patients with symptoms suggestive of an influenza-like illness between december 2011 and april 2012. samples were analyzed with multiplex real-time polymerase chain reaction (rt-pcr) to help identify the causative viral pathogen. a total of 200 patients were enrolled in the study. a respi ...201424105787
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
replication characteristics of swine influenza viruses in precision-cut lung slices reflect the virulence properties of the viruses.precision-cut lung slices of pigs were infected with five swine influenza a viruses of different subtypes (a/sw/potsdam/15/1981 h1n1, a/sw/bad griesbach/idt5604/2006 h1n1, a/sw/bakum/1832/2000 h1n2, a/sw/damme/idt5673/2006 h3n2, a/sw/herford/idt5932/2007 h3n2). the viruses were able to infect ciliated and mucus-producing cells. the infection of well-differentiated respiratory epithelial cells by swine influenza a viruses was analyzed with respect to the kinetics of virus release into the superna ...201324225030
genome sequence of a circulating human-like swine-origin influenza a virus h3n2 strain.the full-genome sequence of a/swine/henan/1/2010, a strain of influenza a virus isolated in central china, was determined. phylogenetic analyses show that its eight genomic segments are human-like, and some of its segments have appeared in swine h1n2, swine h1n1, and human h1n2 influenza viruses.201324233586
substitutions near the receptor binding site determine major antigenic change during influenza virus evolution.the molecular basis of antigenic drift was determined for the hemagglutinin (ha) of human influenza a/h3n2 virus. from 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in ha immediately adjacent to the receptor binding site. most of these substitutions were involved in antigenic change more than once. equivalent positions were responsible for the recent antigenic changes of influenza b and a/h1n1 viruses. substitution of ...201324264991
influenza virus surveillance in pakistan during 2008-2011.there is little information about influenza among the pakistani population. in order to assess the trends of influenza-like-illness (ili) and to monitor the predominant circulating strains of influenza viruses, a country-wide lab-based surveillance system for ili and severe acute respiratory illness (sari) with weekly sampling and reporting was established in 2008. this system was necessary for early detection of emerging novel influenza subtypes and timely response for influenza prevention and ...201324260327
humoral and cellular responses to a non-adjuvanted monovalent h1n1 pandemic influenza vaccine in hospital employees.the efficacy of the h1n1 influenza vaccine relies on the induction of both humoral and cellular responses. this study evaluated the humoral and cellular responses to a monovalent non-adjuvanted pandemic influenza a/h1n1 vaccine in occupationally exposed subjects who were previously vaccinated with a seasonal vaccine.201324238117
different evolutionary trends of swine h1n2 influenza viruses in italy compared to european viruses.european h1n2 swine influenza viruses (eu h1n2sivs) arose from multiple reassortment events among human h1n1, human h3n2, and avian influenza viruses. we investigated the evolutionary dynamics of 53 italian h1n2 strains by comparing them with eu h1n2 sivs. hemagglutinin (ha) phylogeny revealed italian strains fell into four groups: group a and b (41 strains) had a human h1 similar to eu h1n2sivs, which probably originated in 1986. however group b (38 strains) formed a subgroup that had a two-ami ...201324289094
development and evaluation of a sybr green-based real time rt-pcr assay for detection of the emerging avian influenza a (h7n9) virus.most recently a novel avian-origin influenza a (h7n9) virus emerged in china and has been associated with lots of human infection and fatal cases. genetic analysis of the viral genome revealed that this reassortant virus might be better adapted to humans than other avian influenza viruses. molecular diagnostic methods are thus urgently needed in public health laboratories. in this study, a sybr green-based one-step real time reverse transcription-pcr (rt-pcr) was developed to detect the novel h7 ...201324278234
population dynamics of cocirculating swine influenza a viruses in the united states from 2009 to 2012.understanding the ecology and evolution of influenza a viruses (iav) in mammalian hosts is critical to reduce disease burden in production animals and lower zoonotic infection risk in humans. recent advances in influenza surveillance in us swine populations allow for timely epidemiological, phylogenetic, and virological analyses that monitor emergence of novel viruses and assess changes in viral population dynamics.201324224819
swine influenza virus vaccine serologic cross-reactivity to contemporary us swine h3n2 and efficacy in pigs infected with an h3n2 similar to 2011-2012 h3n2v.swine influenza a virus (iav) reassortment with 2009 h1n1 pandemic (h1n1pdm09) virus has been documented, and new genotypes and subclusters of h3n2 have since expanded in the us swine population. an h3n2 variant (h3n2v) virus with the h1n1pdm09 matrix gene and the remaining genes of swine triple reassortant h3n2 caused outbreaks at agricultural fairs in 2011-2012.201324224818
anti-influenza activity of alchemilla mollis extract: possible virucidal activity against influenza virus particles.influenza virus infection is a major public health problem that leads to significant morbidity and mortality. the emergence of resistance to the currently available anti-influenza agents has necessitated the development of new drugs with novel targets. studying known ethno-medicinal plants is a promising approach for the discovery of new antiviral compounds. alchemilla mollis is used in traditional medicine in europe for different indications, including minimizing the symptoms of a sore throat. ...201324270383
severity of the two post-pandemic influenza seasons 2010-11 and 2011-12 in northern greece.since the pandemic in 2009, the two following post pandemic influenza seasons have been associated with increased morbidity and mortality rates in northern greece. the scope of this short report is to provide relevant epidemiological information, an evaluation of the efficacy of the seasonal vaccine and antiviral drugs. molecular analysis revealed the close match of a(h1n1) 2009 pandemic and post-pandemic 2010-11 viruses with the vaccine virus. however, a proportion of the influenza a(h3n2) and ...201324376321
tmprss2 is essential for influenza h1n1 virus pathogenesis in mice.annual influenza epidemics and occasional pandemics pose a severe threat to human health. host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. the cleavage activation of the influenza virus hemagglutinin (ha) by host cell proteases is essential for viral infectivity. however, it is unknown which proteases activate influenza viruses in mammals. several candidates have been identified in cell culture studie ...201324348248
asperterrestide a, a cytotoxic cyclic tetrapeptide from the marine-derived fungus aspergillus terreus scsgaf0162.a new cytotoxic and antiviral cyclic tetrapeptide, asperterrestide a (1), a new alkaloid, terremide c (2), and a new aromatic butenolide, aspernolide e (3), together with 10 known compounds were isolated from the fermentation broth of the marine-derived fungus aspergillus terreus scsgaf0162. their structures were elucidated by spectroscopic analysis, and the absolute configuration of 1 was determined by the mosher ester technique and analysis of the acid hydrolysates using a chiral-phase hplc co ...201323806112
immunomodulatory properties of subcellular fractions of a g+ bacterium, bacillus firmus.mucosal immunization with non-living antigens usually requires the use of an adjuvant. the adjuvant activity of bacillus firmus in the mucosal immunization of mice was described by our laboratory previously. in the present study, subcellular localization of b. firmus activities was followed. after mechanical disintegration, subcellular components of bacterium were fractionated by differential centrifugation and salting out. bacterial cell walls, cytoplasmic membrane fraction, soluble cytoplasmic ...201322875593
phylodynamics of the emergence of influenza viruses after cross-species transmission.human populations are constantly exposed to emerging pathogens such as influenza a viruses that result from cross-species transmissions. generally these sporadic events are evolutionary dead-ends, but occasionally, viruses establish themselves in a new host that offers a novel genomic context to which the virus must adjust to avoid attenuation. however, the dynamics of this process are unknown. here we present a novel method to characterize the time it takes to g+c composition at third codon pos ...201324358190
inhibitory influence of enterococcus faecium on the propagation of swine influenza a virus in vitro.the control of infectious diseases such as swine influenza viruses (swiv) plays an important role in food production both from the animal health and from the public health point of view. probiotic microorganisms and other health improving food supplements have been given increasing attention in recent years, but, no information on the effects of probiotics on swine influenza virus is available. here we address this question by assessing the inhibitory potential of the probiotic enterococcus faec ...201323308134
iridoid and bis-iridoid glucosides from the fruit of gardenia jasminoides.three new iridoid glucosides, 6″-o-trans-feruloylgenipin gentiobioside (1), 2'-o-trans-caffeoylgardoside (2), jasmigeniposide a (3), and one new bis-iridoid glucoside, jasmigeniposide b (4), along with six known analogues (5-10), were isolated from the fruit of gardenia jasminoides. their structures were established on the basis of spectroscopic analyses and chemical methods. anti-virus activity of isolated compounds were evaluated in vitro and only compound 9 showed moderate inhibitory activity ...201323567862
antiviral activity of isatis indigotica root-derived clemastanin b against human and avian influenza a and b viruses in vitro.clemastanin b, 7s,8r,8'r-(-)-lariciresinol-4,4'-bis-o-β-d-glucopyranoside, is one of the major lignans extracted from isatis indigotica root (iir). in this study, the anti-influenza activities of clemastanin b were evaluated in vitro. clemastanin b was found to inhibit different subtypes of human (h1n1, including swine-origin h1n1; h3n2 and influenza b) and avian influenza viruses (h6n2, h7n3, h9n2) at different magnitudes of activity (ic50 0.087-0.72 mg/ml) while this compound was inactive agai ...201323403777
evidence for a crucial role of a host non-coding rna in influenza a virus replication.a growing body of evidence suggests the non-protein coding human genome is of vital importance for human cell function. besides small rnas, the diverse class of long non-coding rnas (lncrnas) recently came into focus. however, their relevance for infection, a major evolutionary driving force, remains elusive. using two commercially available microarray systems, namely ncode™ and sureprint™ g3, we identified differential expression of 42 ncrnas during influenza a virus (iav) infection in human lu ...201324440876
unique gangliosides synthesized in vitro by sialyltransferases from marine bacteria and their characterization: ganglioside synthesis by bacterial sialyltransferases.on the basis of the results outlined in our previous report, bacterial sialyltransferases (st) from marine sources were further characterized using glycosphingolipids (gsl), especially ganglio-series gsls, based on the enzymatic characteristics and kinetic parameters obtained by line weaver-burk plots. among them, ga1 and ga2 were found to be good substrates for these unique sts. thus, new gangliosides synthesized by α2-3 and α2-6sts were structurally characterized by several analytical procedur ...201323220479
inflammatory response of mast cells during influenza a virus infection is mediated by active infection and rig-i signaling.influenza a virus (iav) is a major respiratory pathogen of both humans and animals. the lung is protected from pathogens by alveolar epithelial cells, tissue-resident alveolar macrophages, dendritic cells, and mast cells. the role of alveolar epithelial cells, endothelial cells, and alveolar macrophages during iav infection has been studied previously. in this study, we address the role of mast cells during iav infection. respiratory infection with a/wsn/33 causes significant disease and immunop ...201323526820
prolonged shedding of the canine influenza h3n2 virus in nasal swabs of experimentally immunocompromised dogs.the avian origin canine influenza virus h3n2 has been recently isolated and found to be currently in dog population in south korea and china. the purpose of this study was to clarify the relationship between immunosuppressive glucocorticoids used in veterinary clinical practice and viral shedding pattern of influenza in dogs.201323596593
h1n1, but not h3n2, influenza a virus infection protects ferrets from h5n1 encephalitis.seasonal influenza causes substantial morbidity and mortality because of efficient human-to-human spread. rarely, zoonotic strains of influenza virus spread to humans, where they have the potential to mediate new pandemics with high mortality. we studied systemic viral spread after intranasal infection with highly pathogenic avian influenza virus (h5n1 [a/viet nam/1203/2004]) in ferrets with or without prior pandemic h1n1pdm09 (a/mexico/4108/2009) or h3n2 (a/victoria/361/2011) infection. after i ...201324371072
interleukin-22 reduces lung inflammation during influenza a virus infection and protects against secondary bacterial infection.interleukin-22 (il-22) has redundant, protective, or pathogenic functions during autoimmune, inflammatory, and infectious diseases. here, we addressed the potential role of il-22 in host defense and pathogenesis during lethal and sublethal respiratory h3n2 influenza a virus (iav) infection. we show that il-22, as well as factors associated with its production, are expressed in the lung tissue during the early phases of iav infection. our data indicate that retinoic acid receptor-related orphan r ...201323596287
antiviral responses by swine primary bronchoepithelial cells are limited compared to human bronchoepithelial cells following influenza virus infection.swine generate reassortant influenza viruses because they can be simultaneously infected with avian and human influenza; however, the features that restrict influenza reassortment in swine and human hosts are not fully understood. type i and iii interferons (ifns) act as the first line of defense against influenza virus infection of respiratory epithelium. to determine if human and swine have different capacities to mount an antiviral response the expression of ifn and ifn-stimulated genes (isg) ...201323875024
reassortment ability of the 2009 pandemic h1n1 influenza virus with circulating human and avian influenza viruses: public health risk implications.exploring the reassortment ability of the 2009 pandemic h1n1 (a/h1n1pdm09) influenza virus with other circulating human or avian influenza viruses is the main concern related to the generation of more virulent or new variants having implications for public health. after different coinfection experiments in human a549 cells, by using the a/h1n1pdm09 virus plus one of human seasonal influenza viruses of h1n1 and h3n2 subtype or one of h11, h10, h9, h7 and h1 avian influenza viruses, several reasso ...201323639426
inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (diospyros kaki) on a broad range of viruses.tannins, plant-derived polyphenols and other related compounds, have been utilized for a long time in many fields such as the food industry and manufacturing. in this study, we investigated the anti-viral effects of tannins on 12 different viruses including both enveloped viruses (influenza virus h3n2, h5n3, herpes simplex virus-1, vesicular stomatitis virus, sendai virus and newcastle disease virus) and non-enveloped viruses (poliovirus, coxsachievirus, adenovirus, rotavirus, feline calicivirus ...201323372851
complete genome sequence of a novel reassortant avian influenza h1n2 virus isolated from a domestic sparrow in 2012.we report here the complete genome sequence of a novel h1n2 avian influenza virus strain, a/sparrow /guangxi/gxs-1/2012 (h1n2), isolated from a sparrow in the guangxi province of southern china in 2012. all of the 8 gene segments (hemagglutinin [ha], nucleoprotein [np], matrix [m], polymerase basic 2 [pb2], neuraminidase [na], polymerase acidic [pa], polymerase basic 1 [pb1], and nonstructural [ns] genes) of this natural recombinant virus are attributed to the eurasian lineage, and phylogenetic ...201323868121
genome sequence of a novel reassortant h3n2 avian influenza virus from domestic mallard ducks in eastern china.the h3 subtype avian influenza virus (aiv) can provide genes for human influenza virus through gene reassortment, which raises great concerns in terms of its potential threat to human health. here, we report the complete genome sequence of a novel h3n2 aiv isolated from domestic ducks in the jiangsu province of eastern china in 2004, which is a natural recombinant virus whose genes are derived from h3n8, h5n1, h5n2, h11n2, h4n6, and h1n1 aivs. this genome will help to understand the epidemiology ...201323580713
study of immunogenicity of recombinant proteins based on hemagglutinin and neuraminidase conservative epitopes of influenza a virus.recombinant hemagglutinin (rha) and neurominidase (rna) developed in our investigation are amino acid sequence consensus variants of h1n1 2009 subtype influenza virus strain, also including immunogenic epitopes typical for other influenza virus subtypes (h3n1 and h5n1). substitutions were made: typical for russian virus isolates (in ha - s220t, na - d248n) and in active centers of molecules - r118l, r293l, r368l; c92s, c417s to increase recombinant proteins stability in e. coli. the aim of the p ...201323969554
prokaryote-expressed m2e protein improves h9n2 influenza vaccine efficacy and protection against lethal influenza a virus in mice.influenza vaccines are prepared annually based on global epidemiological surveillance data. however, since there is no method by which to predict the influenza strain that will cause the next pandemic, the demand to develop new vaccination strategies with broad cross-reactivity against influenza viruses are clearly important. the ectodomain of the influenza m2 protein (m2e) is an attractive target for developing a vaccine with broad cross-reactivity. for these reasons, we investigated the effica ...201323551908
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
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