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generation of reassortant influenza viruses within the non-industrial poultry system.we compared the genetic and biologic characteristics of 35 influenza viruses of different epidemiological backgrounds in korea, including h3n2 canine influenza virus (civ). phylogenetic analysis revealed that chicken adapted h9n2 viruses (a/chicken/korea/96006/96 [ck/kor/96006-like]) have acquired aquatic avian gene segments through reassortment, and these reassorted h9n2 viruses were more frequently detected from minor poultry species than from industrial poultry. conversely, gene segments from ...201222386854
age as a determinant for dissemination of seasonal and pandemic influenza: an open cohort study of influenza outbreaks in östergötland county, sweden.an understanding of the occurrence and comparative timing of influenza infections in different age groups is important for developing community response and disease control measures. this study uses data from a scandinavian county (population 427.000) to investigate whether age was a determinant for being diagnosed with influenza 2005-2010 and to examine if age was associated with case timing during outbreaks. aggregated demographic data were collected from statistics sweden, while influenza cas ...201222384066
multifunctional adaptive ns1 mutations are selected upon human influenza virus evolution in the mouse.the role of the ns1 protein in modulating influenza a virulence and host range was assessed by adapting a/hong kong/1/1968 (h3n2) (hk-wt) to increased virulence in the mouse. sequencing the ns genome segment of mouse-adapted variants revealed 11 mutations in the ns1 gene and 4 in the overlapping nep gene. using the hk-wt virus and reverse genetics to incorporate mutant ns gene segments, we demonstrated that all ns1 mutations were adaptive and enhanced virus replication (up to 100 fold) in mouse ...201222363747
pathogenesis and transmission of swine origin a(h3n2)v influenza viruses in ferrets.recent isolation of a novel swine-origin influenza a h3n2 variant virus [a(h3n2)v] from humans in the united states has raised concern over the pandemic potential of these viruses. here, we analyzed the virulence, transmissibility, and receptor-binding preference of four a(h3n2)v influenza viruses isolated from humans in 2009, 2010, and 2011. high titers of infectious virus were detected in nasal turbinates and nasal wash samples of a(h3n2)v-inoculated ferrets. all four a(h3n2)v viruses possesse ...201222355116
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
strain-dependent effects of pb1-f2 of triple-reassortant h3n2 influenza viruses in swine.the pb1-f2 protein of the influenza a viruses (iavs) can act as a virulence factor in mice. its contribution to the virulence of iav in swine, however, remains largely unexplored. in this study, we chose two genetically related h3n2 triple-reassortant iavs to assess the impact of pb1-f2 in virus replication and virulence in pigs. using reverse genetics, we disrupted the pb1-f2 orf of a/swine/wisconsin/14094/99 (h3n2) (sw/99) and a/turkey/ohio/313053/04 (h3n2) (ty/04). removing the pb1-f2 orf led ...201222815274
live attenuated influenza vaccine provides superior protection from heterologous infection in pigs with maternal antibodies without inducing vaccine-associated enhanced respiratory disease.control of swine influenza a virus (iav) in the united states is hindered because inactivated vaccines do not provide robust cross-protection against the multiple antigenic variants cocirculating in the field. vaccine efficacy can be limited further for vaccines administered to young pigs that possess maternally derived immunity. we previously demonstrated that a recombinant a/sw/texas/4199-2/1998 (tx98) (h3n2) virus expressing a truncated ns1 protein is attenuated in swine and has potential for ...201222811541
tenacity of low-pathogenic avian influenza viruses in different types of poultry litter.to determine the risk of infection associated with exposure to low-pathogenic avian influenza (ai) virus-contaminated poultry litter, the tenacity of low pathogenic a/ck/ca/431/00(h6n2), a/mallard/mn/355779/00(h5n2), and a/turkey/ohio/313053/04(h3n2) was evaluated. viral stocks were incubated with poultry litter from commercial flocks at 25°c. three types of poultry litter, wood shavings, shavings plus gypsum, and shavings plus peanut hulls, from commercial broiler flocks were used. the 3 low-pa ...201222802163
synthesis of c-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-aiv activities.with the introduction of bioisosteres of the guanidinium group together with scaffold hopping, 35 zanamivir analogs with c-4-modification were synthesized, and their inhibitory activities against both group-1 and group-2 neuraminidase (h5n1 and h3n2) were determined. compound d26 exerts the most potency, with ic(50) values of 0.58 and 2.72 μm against n2 and n1, respectively. further preliminary anti-avian influenza virus (aiv, h5n1) activities against infected mdck cells were evaluated, and d5 e ...201222795831
neurological picture. sub-acute hydrocephalus in a patient with influenza a (h3n2) virus-related cerebellitis. 201222773858
surface glycoproteins of influenza a h3n2 virus modulate virus replication in the respiratory tract of ferrets.the hemagglutinin (ha) genes of the influenza a h3n2 subtype viruses isolated from 1968 to 2010 have evolved substantially but their neuraminidase (na) genes have been relatively less divergent. the h3n2 viruses isolated since 1995 were found to replicate in the lower respiratory tract of ferrets less efficiently than the earlier isolates. to evaluate whether the ha or/and na or the internal protein gene segments of the h3n2 virus affected viral replication in the respiratory tract of ferrets, r ...201222743127
highly conserved influenza a virus epitope sequences as candidates of h3n2 flu vaccine targets.this study focused on identifying the conserved epitopes in a single subtype a (h3n2)-as candidates for vaccine targets. we identified a total of 32 conserved epitopes in four viral proteins [22 ha, 4pb1, 3 na, 3 np]. evaluation of conserved epitopes in coverage during 1968-2010 revealed that (1) 12 ha conserved epitopes were highly present in the circulating viruses; (2) the remaining 10 ha conserved epitopes appeared with lower percentage but a significantly increasing trend after 1989 [p<0.00 ...201222698979
alkaloids from the root of isatis indigotica.seventeen new alkaloids (1-17) and 14 known analogues have been isolated from an aqueous extract of the root of isatis indigotica. the structures and absolute configurations of these compounds were determined by extensive spectroscopic data analysis, including 2d nmr, single-crystal x-ray crystallography using anomalous scattering of cu kα radiation, and electronic circular dichroism spectra calculations based on the quantum-mechanical time-dependent density functional theory. compounds 1, 2, an ...201222694318
annual influenza vaccination affects the development of heterosubtypic immunity.annual vaccination of healthy children >6 months of age against seasonal influenza has been recommended by public health authorities of some countries. however, currently used seasonal vaccines provide only limited protection against (potentially) pandemic influenza viruses. furthermore, we recently hypothesized that annual vaccination may hamper the development of cross-reactive immunity against influenza a viruses of novel subtypes, that would otherwise be induced by natural infection. here we ...201222643217
prophylactic and therapeutic combination effects of rimantadine and oseltamivir against influenza virus a (h3n2) infection in mice.the combined effect of rimantadine and oseltamivir in a prophylactic context (therapy beginning 4 h pre-virus infection) and therapeutic context (therapy started at 24 h post-viral inoculation) course on influenza h3n2 virus infection in mice was studied. in the prophylactic course 5 and 10 mg/kg/day rimantadine with 0.2 and 0.4 mg/kg/day (25:1 dose ratio) oseltamivir showed a protection index (pi) of 79.6% and 75%, respectively and a mean survival time (mst) of 13.1 and 12.9 days. the individua ...201222617756
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
constrained evolution drives limited influenza diversity.h3n2 influenza a viruses have been widely circulating in human populations since the pandemic of 1968. a striking feature of the evolutionary development of this strain has been its 'canalized' nature, with narrow evolutionary trees dominated by long trunks with few branching, or bifurcation events and a consequent lack of standing diversity at any single point. this is puzzling, as one might expect that the strong human immune response against the virus would create an environment encouraging m ...201222613866
age-dependent prevalence of antibodies cross-reactive to the influenza a(h3n2) variant virus in sera collected in norway in 2011.antibody cross-reactivity to the influenza a(h3n2) variant virus recently reported in the united states, was investigated in norwegian sera. seroprevalence was 40% overall, and 71% in people born between 1977 and 1993. the most susceptible age groups were children and people aged around 50 years. the high immunity in young adults is likely to be due to strong priming infection with similar viruses in the 1990s. more research is needed to explain the poor immunity in 45–54 year-olds.201222607964
immune responses and protection efficacy of a recombinant swinepox virus expressing ha1 against swine h3n2 influenza virus in mice and pigs.swine influenza virus (siv) is not only an important respiratory pathogen in pigs but also a potent threat to human health. even though immunization with recombinant vaccinia poxviruses expressing protective antigens as a vaccination strategy has been widely used for many infectious diseases, development of recombinant swinepox virus (rspv) vector for this purpose has been less successful. here, we report the construction of a recombinant swinepox virus (rspv) expressing hemagglutinin (ha1) of h ...201222584406
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
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
[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
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
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
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
fatal case of reye's syndrome associated with h3n2 influenza virus infection and salicylate intake in a 12-year-old patient.we describe a fatal case of reye's syndrome in a 12-year-old male patient during an influenza a (h3n2) infection for which he received salicylates. in the current situation of the novel a/h1n1 virus pandemic, we believe that it is of high importance to emphasize the risks associated with salicylate intake to avoid the reappearance of reye's syndrome.201120167009
detection of viruses via statistical gene expression analysis.we develop a new bayesian construction of the elastic net (enet), with variational bayesian analysis. this modeling framework is motivated by analysis of gene expression data for viruses, with a focus on h3n2 and h1n1 influenza, as well as rhino virus and rsv (respiratory syncytial virus). our objective is to understand the biological pathways responsible for the host response to such viruses, with the ultimate objective of developing a clinical test to distinguish subjects infected by such viru ...201120643599
virological surveillance and preliminary antigenic characterization of influenza viruses in pigs in five european countries from 2006 to 2008.this study presents the results of the virological surveillance for swine influenza viruses (sivs) in belgium, uk, italy, france and spain from 2006 to 2008. our major aims were to clarify the occurrence of the three siv subtypes - h1n1, h3n2 and h1n2 - at regional levels, to identify novel reassortant viruses and to antigenically compare sivs with human h1n1 and h3n2 influenza viruses. lung tissue and/or nasal swabs from outbreaks of acute respiratory disease in pigs were investigated by virus ...201120042068
direct pathogen detection from swab samples using a new high-throughput sequencing technology.the detection of emerging infectious diseases has been a continuing concern, especially with the novel influenza a (h1n1) viral pandemic of 2009. in the present study, we validated a 'second-generation' parallel sequencing platform for viral detection in swab samples collected during recent influenza virus infections in beijing. this operation yielded millions of valid reads per sample and resulted in an almost complete spectrum of nucleotide information. importantly, novel a (h1n1) and seasonal ...201120412188
vaxcinetm: an oil-based adjuvant for influenza vaccines.vaccination is the method of choice for the prevention of influenza infection. however, the quantity of the antigen available, especially in the case of pandemics, often fails to meet the global demand. however, improved adjuvants can overcome this problem. preliminary results obtained in this study revealed that one year after a single subcutaneous immunisation with influenza a h3n2 virus in an oil-based carrier, vaxcinetm, outbreed mice produced a high immunoglobulin g response that lasted for ...201122241133
rapid identification of neuraminidase inhibitor resistance mutations in seasonal influenza virus a(h1n1), a(h1n1)2009, and a(h3n2) subtypes by melting point analysis.the high mutation rate of influenza virus, combined with the increasing worldwide use of influenza virus-specific drugs, allows the selection of viruses that are resistant to the currently available antiviral medications. therefore, reliable tests for the rapid detection of drug-resistant influenza virus strains are required. we evaluated the use of a procedure involving real-time polymerase chain reaction (pcr) followed by melting point analysis (mpa) of hybrids formed between the pcr product a ...201122089329
genetic evolution of low pathogenecity h9n2 avian influenza viruses in tunisia: acquisition of new mutations.since the end of 2009, h9n2 has emerged in tunisia causing several epidemics in poultry industry resulting in major economic losses. to monitor variations of influenza viruses during the outbreaks, tunisian h9n2 virus isolates were identified and genetically characterized.201121992186
Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice.A mouse model was used to determine if protective immunity to influenza A virus infection differs between the sexes. The median lethal dose of H1N1 or H3N2 was lower for naïve females than males. After a sublethal, primary infection with H1N1 or H3N2, females and males showed a similar transient morbidity, but females generated more neutralizing and total anti-influenza A virus antibodies. Immunized males and females showed similar protection against secondary challenge with a homologous virus, ...201121983155
safety and immunogenicity of a new trivalent inactivated split-virus influenza vaccine in healthy korean children: a randomized, double-blinded, active-controlled, phase iii study.we report results of a randomized, double-blinded, active-controlled, phase iii study conducted to evaluate the immunogenicity and safety of a new trivalent inactivated split-virus influenza vaccine (gc501) manufactured by the green cross corporation in korea. a total of 283 healthy children aged 6 months to < 18 yr were randomized to receive either gc501 or control. of the gc501 recipients, seroconversion occurred in 48.5% for a/h1n1, 67.7% for a/h3n2 and 52% for influenza b. the proportion of ...201122065897
infection of differentiated porcine airway epithelial cells by influenza virus: differential susceptibility to infection by porcine and avian viruses.swine are important hosts for influenza a viruses playing a crucial role in the epidemiology and interspecies transmission of these viruses. respiratory epithelial cells are the primary target cells for influenza viruses.201122174804
discovery of potential m2 channel inhibitors based on the amantadine scaffold via virtual screening and pharmacophore modeling.the m2 channel protein on the influenza a virus membrane has become the main target of the anti-flu drugs amantadine and rimantadine. the structure of the m2 channel proteins of the h3n2 (pdb code 2rlf) and 2009-h1n1 (genbank accession number gq385383) viruses may help researchers to solve the drug-resistant problem of these two adamantane-based drugs and develop more powerful new drugs against influenza a virus. in the present study, we searched for new m2 channel inhibitors through a combinati ...201122158591
In vitro and in vivo efficacy of fluorodeoxycytidine analogs against highly pathogenic avian influenza H5N1, seasonal, and pandemic H1N1 virus infections.Various fluorodeoxyribonucleosides were evaluated for their antiviral activities against influenza virus infections in vitro and in vivo. Among the most potent inhibitors was 2'-deoxy-2'-fluorocytidine (2'-FdC). It inhibited various strains of low and highly pathogenic avian influenza H5N1 viruses, pandemic H1N1 viruses, an oseltamivir-resistant pandemic H1N1 virus, and seasonal influenza viruses (H3N2, H1N1, influenza B) in MDCK cells, with the 90% inhibitory concentrations ranging from 0.13 to ...201121925541
[the 50% effective dose (ed50a) of seasonal spilt influenza vaccine in mice].to evaluate the seasonal influenza spilt vaccine's immunogenicity and the 50% effective dose (ed50a) of hemagglutin (ha) that can make 50% of the mice hemagglutination inhibition antibody (hi) titers to 40.201121863626
Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays.Please cite this paper as: Cwach et al. (2011) Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00283.x. Background Prior to detection of an antibody response toward influenza viruses using the hemagglutination inhibition assay (HAI), sera are routinely treated to inactivate innate inhibitors using both heat inactivation (56°C) and recombinant neuraminidase [receptor-des ...201121883963
History of Swine Influenza Viruses in Asia.The pig is one of the main hosts of influenza A viruses and plays important roles in shaping the current influenza ecology. The occurrence of the 2009 H1N1 pandemic influenza virus demonstrated that pigs could independently facilitate the genesis of a pandemic influenza strain. Genetic analyses revealed that this virus was derived by reassortment between at least two parent swine influenza viruses (SIV), from the northern American triple reassortant H1N2 (TR) and European avian-like H1N1 (EA) li ...201121948002
Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety.Please cite this paper as: Tavana et al. (2011) Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00290.x. Background Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to var ...201121955954
[Evolutionary changes in the NA and HA genes of H3N2 influenza virus in the Moscow Region during 2003-2009].During the winter 2009 outbreak in the Moscow Region, H3N2 influenza viruses were isolated from the nasopharyngeal washes of patients via their propagation in the human intestinal (Caco-2) and bronchial (Calu-3) epithelial cell cultures maintaining the proteolytic cleavage of HA0--> HA1+HA2 and multicycle virus replication. Analysis of the nucleotide sequences of virus RNA indicated that the 2009 viruses differed from those isolated in 2003 in 14 and 21 amino acids of the neuraminidase (NA) and ...201122171471
comparative analyses of pandemic h1n1 and seasonal h1n1, h3n2, and influenza b infections depict distinct clinical pictures in ferrets.influenza a and b infections are a worldwide health concern to both humans and animals. high genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause illness variation. since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. here we infected ferrets with 13 currently circulating influenza strains (including strains of ...201122110664
adaptation of a duck influenza a virus in quail.quail are thought to serve as intermediate hosts of influenza a viruses between aquatic birds and terrestrial birds, such as chickens, due to their high susceptibility to aquatic-bird viruses, which then adapt to replicate efficiently in their new hosts. however, does replication of aquatic-bird influenza viruses in quail similarly result in their efficient replication in humans? using sialic acid-galactose linkage-specific lectins, we found both avian (sialic acid-α2-3-galactose [siaα2-3gal] li ...201122090115
[Study on the mutations within the whole genome of influenza virus subtype A/H3N2 strains circulated in Zhejiang province from 1998 to 2009].To analyze the consistency of evolution condition between HA gene and the whole genome of influenza virus subtype A/H3N2 strains isolated in Zhejiang province from 1998 to 2009, and to study the potential antigenic region on the whole genome.201122041565
Emergence and dissemination of a swine H3N2 reassortant with 2009 pandemic H1N1 genes in pigs in China.The 2009 pandemic influenza virus (pdm/09) has been frequently introduced to pigs and has reassorted with other swine viruses. Recently, H3N2 reassortants with pdm/09-like internal genes were isolated in Guangxi and Hong Kong. Genetic and epidemiological analyses suggest that these viruses have circulated in swine for some time. This is the first evidence that swine reassortant viruses with pdm/09-like genes may have become established in the field, altering the landscape of human and swine infl ...201122171260
[Comparative immunogenicity studies of cultural and peptide influenza vaccines].Comparative immunogenicity studies of experimental vaccines based onA/Aichi/2/68 neuraminidase peptide fragments (NA) and influenza virus A and B strains produced in MDCK cell culture.201122145349
Differential pulmonary transcriptomic profiles in murine lungs infected with low and highly virulent influenza H3N2 viruses reveal dysregulation of TREM1 signaling, cytokines, and chemokines.Investigating the relationships between critical influenza viral mutations contributing to increased virulence and host expression factors will shed light on the process of severe pathogenesis from the systems biology perspective. We previously generated a mouse-adapted, highly virulent influenza (HVI) virus through serial lung-to-lung passaging of a human influenza H3N2 virus strain that causes low virulent influenza (LVI) in murine lungs. This HVI virus is characterized by enhanced replication ...201121874528
molecular epidemiology of influenza a/h3n2 viruses circulating in uganda.the increasing availability of complete influenza virus genomes is deepening our understanding of influenza evolutionary dynamics and facilitating the selection of vaccine strains. however, only one complete african influenza virus sequence is available in the public domain. here we present a complete genome analysis of 59 influenza a/h3n2 viruses isolated from humans in uganda during the 2008 and 2009 season. isolates were recovered from hospital-based sentinel surveillance for influenza-like i ...201122132146
epitope peptides of influenza h3n2 virus neuraminidase gene designed by immunoinformatics.the virus surface protein neuraminidase (na) is a main subtype-specific antigen in influenza type a viruses. neuraminidase functions as an enzyme to break the bonds between hemagglutinin (ha) and sialic acid to release newly formed viruses from infected cells. in this study, na genes from the h3n2 subtype virus were sequenced and na proteins were screened for b-cell epitopes and assessed based on immunoinformatics. based on this information, three peptides es8, rr9, and wk7 (covering amino acid ...201122107789
Efficacy of trivalent inactivated influenza vaccines in the cotton rat Sigmodon hispidus model.Annually adjusted inactivated influenza vaccines can prevent infection and limit the spread of seasonal influenza when vaccine strain closely matches circulating strain. For the years when the match is difficult to achieve, a rapid screening of a larger repertoire of vaccines may be required but is difficult to accomplish due to the lack of a convenient small animal model of seasonal influenza vaccines. The goal of this work was to determine whether the cotton rat Sigmodon hispidus, a small labo ...201122210139
Antigenic variability in Neuraminidase protein of Influenza A/H3N2 vaccine strains (1968 - 2009).Antigenic drift and shift involving the surface proteins of Influenza virus gave rise to new strains that caused epidemics affecting millions of people worldwide over the last hundred years. Variations in the membrane proteins like Hemagglutinin (HA) and Neuraminidase (NA) necessitates new vaccine strains to be updated frequently and poses challenge to effective vaccine design. Though the HA protein, the primary target of the human immune system, has been well studied, reports on the antigenic v ...201121938209
the dba.2 mouse is susceptible to disease following infection with a broad, but limited, range of influenza a and b viruses.we assessed the relative susceptibilities to disease of the dba.2 and c57bl/6 mouse models upon infection with a range of influenza a and b viruses. dba.2 mice were more susceptible to disease upon inoculation with human h1n1 influenza a virus strains, several swine influenza viruses, and influenza b viruses but were not overtly susceptible to infection with human seasonal h3n2 strains. hemagglutination inhibition and immunoglobulin isotype profiling indicated that dba.2 and c57bl/6 mice generat ...201121917963
diagnostic capacity of rapid influenza antigen test: reappraisal with experience from the 2009 h1n1 pandemic.background: the rapid influenza antigen test (riat) has been questioned because of its poor sensitivity. clinicians are confused as to what diagnostic help it may provide. riat was reappraised by other laboratory confirmatory tests for its diagnostic capacity. methods: records of riat, rt-pcr and virus culture, performed for upper respiratory tract samples during the period from july 2009 to january 2010, were reviewed. the sensitivity, specificity, positive predictive value (ppv) and negative p ...201122177367
FluReF, an automated flu virus reassortment finder based on phylogenetic trees.Reassortments are events in the evolution of the genome of influenza (flu), whereby segments of the genome are exchanged between different strains. As reassortments have been implicated in major human pandemics of the last century, their identification has become a health priority. While such identification can be done "by hand" on a small dataset, researchers and health authorities are building up enormous databases of genomic sequences for every flu strain, so that it is imperative to develop ...201121989112
Outbreak of swine influenza in Argentina reveals a non-contemporary human H3N2 virus highly transmissible among pigs.Sporadic outbreaks of human H3N2 influenza A virus (IAV) infections in swine populations have been reported in Asia, Europe and North America since 1970. In South America, serological surveys in pigs indicate that IAVs of the H3 and H1 subtypes are currently in circulation; however, neither virus isolation nor characterization has been reported. In November 2008, an outbreak of respiratory disease in pigs consistent with swine influenza virus (SIV) infection was detected in Argentina. The curren ...201121849519
subtyping influenza a virus with monoclonal antibodies and an indirect immunofluorescence assay.the recent association of certain influenza a virus subtypes with clinically relevant phenotypes has led to the increasing importance of subtyping by clinical virology laboratories. to provide clinical laboratories with a definitive immunofluorescence assay for the subtyping of influenza a virus isolates, we generated a panel of monoclonal antibodies (mabs) against the major circulating influenza a virus subtypes using multiple inactivated h1n1, h3n2, and 2009 h1n1 strains individually as immuno ...201122075584
in vitro generation of influenza-specific polyfunctional cd4(+) t cells suitable for adoptive immunotherapy.abstract background aims. influenza viruses cause potentially fatal respiratory infections in stem cell transplant patients. specific t cells provide long-lived host adaptive immunity to influenza viruses, and the potential for generating such cells for clinical use was investigated. methods. the inactivated influenza vaccine (fluvax) approved for human use was used as the antigen source. monocyte-derived dendritic cells pulsed with fluvax were used to stimulate autologous peripheral blood mon ...201121954837
Patterns of predicted T-cell epitopes associated with antigenic drift in influenza H3N2 hemagglutinin.Antigenic drift allowing escape from neutralizing antibodies is an important feature of transmission and survival of influenza viruses in host populations. Antigenic drift has been studied in particular detail for influenza A H3N2 and well defined antigenic clusters of this virus documented. We examine how host immunogenetics contributes to determination of the antibody spectrum, and hence the immune pressure bringing about antigenic drift. Using uTOPE™ bioinformatics analysis of predicted MHC b ...201122039539
development of an antigen-capture enzyme-linked immunosorbent assay using monoclonal antibodies for detecting h6 avian influenza viruses.the h6 subtype of avian influenza virus (aiv) infection occurs frequently in wild and domestic birds. aiv antigen detection is preferred for controlling aiv as birds are infected before they produce antibodies. the purpose of this study was to develop an early diagnostic method for aiv detection. six monoclonal antibodies (mabs) developed from a field h6n1 aiv strain were tested for their ability to bind to viruses. the two that showed the greatest binding ability to aivs were used for antigen d ...201122206824
rohlin distance and the evolution of influenza a virus: weak attractors and precursors.the evolution of the hemagglutinin amino acids sequences of influenza a virus is studied by a method based on an informational metrics, originally introduced by rohlin for partitions in abstract probability spaces. this metrics does not require any previous functional or syntactic knowledge about the sequences and it is sensitive to the correlated variations in the characters disposition. its efficiency is improved by algorithmic tools, designed to enhance the detection of the novelty and to red ...201122162994
Limited Human-to-Human Transmission of Novel Influenza A (H3N2) Virus - Iowa, November 2011.On November 20, 2011, CDC confirmed three cases of swine-origin triple reassortant influenza A (H3N2) (S-OtrH3N2) virus infection in children in two counties in Iowa. None of the children were hospitalized, and each has recovered from a mild episode of febrile respiratory illness. All three were in contact with one another, and none had a known recent exposure to swine. No additional human infections with this virus have been detected in Iowa, and no evidence of sustained human-to-human transmis ...201122129996
pandemic novel 2009 h1n1 influenza: what have we learned?in march 2009, cases of influenza-like illness in mexico caused by a novel h1n1 virus containing genes from swine, avian, and human influenza strains were reported. within several weeks, 2009 h1n1 disseminated rapidly and was the predominant influenza strain globally. on june 11, 2009, the world health organization declared that criteria for an influenza pandemic had been met. concern that this pandemic would rival the 1918 pandemic was high. fortunately, that was not the case. influenza-related ...201121858744
A plant-based system for rapid production of influenza vaccine antigens.Please cite this paper as: Shoji et al. (2011) A plant-based system for rapid production of influenza vaccine antigens. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00295.x. Background Influenza virus is a globally important respiratory pathogen that causes a high degree of annual morbidity and mortality. Significant antigenic drift results in emergence of new, potentially pandemic, virus variants. The best prophylactic option for controlling emerging virus strains is t ...201121974811
emergence of a new swine h3n2 and pandemic (h1n1) 2009 influenza a virus reassortant in two canadian animal populations, mink and swine.a swine h3n2 (swh3n2) and pandemic (h1n1) 2009 (ph1n1) influenza a virus reassortant (swh3n2/ph1n1) was detected in canadian swine at the end of 2010. simultaneously, a similar virus was also detected in canadian mink based on partial viral genome sequencing. the origin of the new swh3n2/ph1n1 viral genes was related to the north american swh3n2 triple-reassortant cluster iv (for hemagglutinin [ha] and neuraminidase [na] genes) and to ph1n1 for all the other genes (m, np, ns, pb1, pb2, and pa). ...201122012020
[High-yield reassortant virus containing hemagglutinin and neuraminidase genes of pandemic influenza A/Moscowl/01/2009 (H1N1) virus].The crossing of influenza A/Moscow/01/2009 (H1N1) virus and reassortant strain X31 (H3N2) containing the genes of internal and non-structural proteins of A/Puerto Rico/8/34 (H1N1) strain gave rise to reassortant virus ReM8. The reassortant contained hemagglutinin (HA) and neuraminidase (NA) genes of pandemic 2009 influenza virus and 6 genes of high-yield A/Puerto Rico/8/34 (H1N1) strain. The reassortant ReM8 produced higher yields in the embryonated chicken eggs than the parent pandemic virus, a ...201121899062
Absence of Influenza A(H1N1) During Seasonal and Pandemic Seasons in a Sentinel Nursing Home Surveillance Network in the Netherlands.To describe the epidemiological, virological, and institutional characteristics of influenza-like illness (ILI) in nursing homes (NHs).201122091963
In vitro anti-viral effect of ß-santalol against influenza viral replication.The anti-influenza A/HK (H3N2) virus activity of ß-santalol was evaluated in MDCK cells and investigated the effect of ß-santalol on synthesis of viral mRNAs. ß-Santalol was investigated for its antiviral activity against influenza A/HK (H3N2) virus using a cytopathic effect (CPE) reduction method. ß-Santalol exhibited anti-influenza A/HK (H3N2) virus activity of 86% with no cytotoxicity at the concentration of 100µg/ml reducing the formation of a visible CPE. Oseltamivir also showed moderate an ...201122192867
Live attenuated influenza vaccine (FluMist®; Fluenz™): a review of its use in the prevention of seasonal influenza in children and adults.Live attenuated influenza vaccine (LAIV) is an intranasally administered trivalent, seasonal influenza vaccine that contains three live influenza viruses (two type A [H1N1 and H3N2 subtypes] and one type B). LAIV was effective in protecting against culture-confirmed influenza caused by antigenically matched and/or distinct viral strains in children aged =71 months enrolled in three phase III trials. LAIV was superior to trivalent inactivated influenza vaccine (TIV) in protecting against influenz ...201121861544
Dose-Response Assessment for Influenza A Virus Based on Data Sets of Infection with its Live Attenuated Reassortants.Reported data sets on infection of volunteers challenged with wild-type influenza A virus at graded doses are few. Alternatively, we aimed at developing a dose-response assessment for this virus based on the data sets for its live attenuated reassortants. Eleven data sets for live attenuated reassortants that were fit to beta-Poisson and exponential dose-response models. Dose-response relationships for those reassortants were characterized by pooling analysis of the data sets with respect to vir ...201121977924
Emergence of novel reassortant H3N2 swine influenza viruses with the 2009 pandemic H1N1 genes in the United States.Reassortant H1 swine influenza viruses (SIVs) carrying 2009 pandemic H1N1 virus (pH1N1) genes have been isolated from pigs worldwide. Seven novel reassortant H3N2 SIVs were identified from diseased pigs in the USA from winter 2010 to spring 2011. These novel viruses contain three or five internal genes from pH1N1 and continue to circulate in swine herds. The emergence of novel reassortant H3N2 SIVs demonstrates reassortment between pH1N1 and endemic SIVs in pigs and justifies continuous surveill ...201122198410
novel antiviral activity of neuraminidase inhibitors against an avian influenza a virus.abstract:201121851647
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